Cl- as a bona fide signalling ion.
m S Abstract Cl- is the major extracellular (Cl-out) and intracellular (Cl-in) anion whose concentration is actively regulated by multiple transporters. These transporters generate Cl- gradients across the plasma membrane and between the cytoplasm and intracellular organelles. [Cl-]in changes rapidly in response to cell stimulation and influences many physiological functions as well as cellular and systemic homeostasis. However, less appreciated is the signaling function of Cl-. Cl- interacts with multiple proteins to directly modify their activity. This review highlights the signaling function of Cl- and argues t...
Source: Am J Physiol Cell Ph... - November 6, 2019 Category: Cytology Authors: Lüscher BP, Vachel L, Ohana E, Muallem S Tags: Am J Physiol Cell Physiol Source Type: research

Extracellular vesicles as biomarkers and therapeutic targets for cancer.
Abstract Extracellular vesicles (EVs) are small lipid membrane vesicles that are secreted from almost all kinds of cells into the extracellular space. EVs are widely accepted to be involved in various cellular processes; in particular, EVs derived from cancer cells have been reported to play important roles in modifying the tumor microenvironment and promoting tumor progression. In addition, EVs derived from cancer cells encapsulate various kinds of tumor-specific molecules, such as proteins and RNAs, which contribute to cancer malignancy. Therefore, unveiling the precise mechanism of intercellular communication v...
Source: Am J Physiol Cell Ph... - November 6, 2019 Category: Cytology Authors: Urabe F, Kosaka N, Ito K, Kimura T, Egawa S, Ochiya T Tags: Am J Physiol Cell Physiol Source Type: research

Dysregulation of the glutaredoxin/S-glutathionylation redox axis in lung diseases.
Abstract Glutathione is a major redox buffer, reaching millimolar concentrations within cells and high micromolar concentrations in airways. While glutathione has been traditionally known as an antioxidant defense mechanism that protects the lung tissue from oxidative stress, glutathione more recently has become recognized for its ability to become covalently conjugated to reactive cysteines within proteins, a modification known as S-glutathionylation (or S-glutathiolation or protein mixed disulfide). S-glutathionylation has the potential to change the structure and function of the target protein, owing to its siz...
Source: Am J Physiol Cell Ph... - November 6, 2019 Category: Cytology Authors: Chia SB, Elko EA, Aboushousha R, Manuel AM, van de Wetering C, Druso JE, van der Velden J, Seward DJ, Anathy V, Irvin CG, Lam YW, van der Vliet A, Janssen-Heininger Y Tags: Am J Physiol Cell Physiol Source Type: research

Long Non-coding RNA MALAT1 Promotes Angiogenesis and Immunosuppressive Properties of HCC Cells by sponging miR-140.
CONCLUSIONS: In summary, this study revealed the mechanisms by which MALAT1 worked as a putative HCC promotor via inhibiting miR-140. Therefore, targeting MALAT1 or miR-140 might alleviate the progression of HCC in future. PMID: 31693399 [PubMed - as supplied by publisher] (Source: Am J Physiol Cell Ph...)
Source: Am J Physiol Cell Ph... - November 6, 2019 Category: Cytology Authors: Hou ZH, Xu XW, Fu XY, Zhou LD, Liu SP, Tan DM Tags: Am J Physiol Cell Physiol Source Type: research

Long noncoding RNA KCNQ1OT1 induces pyroptosis in diabetic corneal endothelial keratopathy.
Abstract Diabetic corneal endothelial keratopathy is an intractable ocular complication which seriously threaten vision. It has been suggested that diabetes is associated with pyroptosis, a type of inflammatory programmed cell death. Long noncoding RNA KCNQ1OT1 is involved in pathophysiological mechanisms of diabetic complications, including diabetic cardiomyopathy and diabetic retinopathy. The aim of this study was to investigate the mechanisms of KCNQ1OT1 in diabetic corneal endothelial keratopathy. Here, we reveal that KCNQ1OT1 and pyroptosis can be triggered in diabetic human and rats corneal endothelium, alon...
Source: Am J Physiol Cell Ph... - November 6, 2019 Category: Cytology Authors: Zhang Y, Song Z, Li X, Xu S, Zhou S, Jin X, Zhang H Tags: Am J Physiol Cell Physiol Source Type: research

Identification and characterization of the Atlantic Salmon Peptide Transporter 1a.
rri T Abstract Peptide Transporter 1 (PepT1) mediates the uptake of dietary di/tripeptides in vertebrates. But, in teleost fish gut more than one PepT1-type transporter might operate, due to teleost-specific whole gen(om)e duplication event(s) occurred during evolution. Here, we describe a novel teleost di/tripeptide transporter, i.e. the Atlantic salmon (Salmo salar) Peptide Transporter 1a (PepT1a; or Solute carrier family 15 member a1, Slc15a1a), which is a paralogue (77% similarity, 64% identity at the amino acid level) of the well-described Atlantic salmon Peptide Transporter 1b (PepT1b, alias PepT1; or Solute...
Source: Am J Physiol Cell Ph... - October 30, 2019 Category: Cytology Authors: Gomes AS, Vacca F, Cinquetti R, Murashita K, Barca A, Bossi E, Rønnestad I, Verri T Tags: Am J Physiol Cell Physiol Source Type: research

E-Cigarette Use Increases Susceptibility to Bacterial Infection by Impairment of Human Neutrophil Chemotaxis, Phagocytosis and NET Formation.
Abstract E-cigarettes are portrayed as safer relative to conventional tobacco. However, burgeoning evidence suggests that E-cigarettes may adversely affect host defenses. However, the precise mechanisms by which E-cigarette vapor alters innate immune cell function have not been fully elucidated. We determined the effects of E-cigarette exposure on the function and responses to infectious challenge of the most abundant innate immune cell, the neutrophil, using isolated human neutrophils and a mouse model of Gram-negative infection. Our results revealed that human neutrophils exposed to E-cigarette vapor had 4.2-fol...
Source: Am J Physiol Cell Ph... - October 30, 2019 Category: Cytology Authors: Corriden R, Moshensky A, Bojanowski CM, Meier A, Chien J, Nelson RK, Crotty Alexander LE Tags: Am J Physiol Cell Physiol Source Type: research

The AGR2 interactome.
Abstract The Anterior Gradient-2 (AGR2) is an Endoplasmic Reticulum (ER)-resident protein belonging to the Protein Disulfide Isomerase (PDI) family which mediates the formation of disulfide bonds, and assists the protein quality control in the ER. In addition to its role in proteostasis, extracellular AGR2 is responsible for various cellular effects in many types of cancer, including cell proliferation, survival, and metastasis. Various OMICs approaches have been used to identify AGR2 binding partners and to investigate the functions of AGR2 in the ER and outside the cell. Emerging data showed that AGR2 exists not...
Source: Am J Physiol Cell Ph... - October 23, 2019 Category: Cytology Authors: Delom F, Mohtar MA, Hupp T, Fessart D Tags: Am J Physiol Cell Physiol Source Type: research

Nucleolin Mediates the Binding of Cancer Cells to L-selectin under Conditions of Lymphodynamic Shear Stress.
Abstract Head and neck squamous cell carcinoma (HNSCC) cells bind to lymphocytes via L-selectin in a shear-dependent manner. This interaction takes place exclusively under low shear stress conditions, such as those found within the lymph node parenchyma. This represents a novel functional role for L-selectin/selectin ligand interactions. Our previous work has characterized as of yet unidentified L-selectin ligands expressed by HNSCC cells that are specifically active under conditions of low shear stress consistent with lymph flow. Using an affinity purification approach, we now show that nucleolin expressed on the...
Source: Am J Physiol Cell Ph... - October 23, 2019 Category: Cytology Authors: Goldson TM, Turner KL, Huang Y, Carlson GE, Caggiano EG, Oberhauser AF, Fennewald SM, Burdick MM, Resto VA Tags: Am J Physiol Cell Physiol Source Type: research

Synergistic activation of mitochondrial metabolism and the glutathione redox couple protects HepG2 hepatocarcinoma cells from palmitoylcarnitine-induced stress.
Abstract Fatty acid stress can have divergent effects in various cancers. We explored how metabolic and redox flexibility in HepG2 hepatocarcinoma cells mediate protection from palmitoylcarnitine. HepG2 cells, along with HCT 116 and HT29 colorectal cancer cells were incubated with 100μM palmitoylcarnitine for up to 48hrs. Mitochondrial H2O2 emission, glutathione and cell survival were assessed in HT29 and HepG2 cells. 100μM palmitoylcarnitine promoted early growth in HepG2 cells by ~8% after 48hrs vs decreased cell survival observed in HT29 and HCT 116 cells. Palmitoylcarnitine increased mitochondrial respir...
Source: Am J Physiol Cell Ph... - October 16, 2019 Category: Cytology Authors: Turnbull PC, Dehghani AC, Theriau CF, Connor MK, Perry CGR Tags: Am J Physiol Cell Physiol Source Type: research

Five months of voluntary wheel running downregulates skeletal muscle LINE-1 gene expression in rats.
Abstract Transposable elements (TEs) are mobile DNA and constitute approximately half of the human genome. LINE-1 (L1) is the only active autonomous TE in the mammalian genome and has been implicated in a number of diseases as well as aging. We have previously reported skeletal muscle L1 expression is lower following acute and chronic exercise training in humans. Herein, we used a rodent model of voluntary wheel running to determine if long-term exercise training affects markers of skeletal muscle L1 regulation. Selectively-bred high running female Wistar rats (n=11 per group) were either given access to a running...
Source: Am J Physiol Cell Ph... - October 16, 2019 Category: Cytology Authors: Romero MA, Mumford PW, Roberson PA, Osburn SC, Parry HA, Kavazis AN, Gladden LB, Schwartz TS, Baker BA, Toedebusch RG, Childs TE, Booth FW, Roberts MD Tags: Am J Physiol Cell Physiol Source Type: research

Secreted Wnt6 mediates diabetes-associated centrosome amplification via its receptor FZD4.
In conclusion, our results showed that the pathophysiological factors in type 2 diabetes, including AGEs, were able to induce centrosome amplification. It is suggested that secreted Wnt6 binds to FZD4 to activate the canonical Wnt6 signaling pathway which is upstream of ROCK1 and 14-3-3σ, which is the cell signaling pathway underlying the diabetes-associated centrosome amplification. PMID: 31618077 [PubMed - as supplied by publisher] (Source: Am J Physiol Cell Ph...)
Source: Am J Physiol Cell Ph... - October 16, 2019 Category: Cytology Authors: He QJ, Wang P, Liu Q, Wu Q, Li YF, Wang J, Lee SC Tags: Am J Physiol Cell Physiol Source Type: research

The load dependence and the force-velocity relation in intact myosin filaments from skeletal and smooth muscles.
Abstract In the present study we evaluated the load dependence of force produced by isolated muscle myosin filaments interacting with fluorescently labeled actin filaments, using for the first time, whole native myosin filaments. This was made possible by using a newly developed approach that allowed the use of physiological levels of ATP. Single filaments composed of either skeletal or smooth muscle myosinand single filaments of actin were attached between pairs of nano-fabricated cantilevers of known stiffness. The filaments were brought into contact to produce force, which caused sliding of the actin filaments ...
Source: Am J Physiol Cell Ph... - October 16, 2019 Category: Cytology Authors: Cheng YS, Leite FS, Rassier DE Tags: Am J Physiol Cell Physiol Source Type: research

microRNA-451a prevents activation of matrix metalloproteinases 2/9 in human cardiomyocytes during pathological stress stimulation.
al MA Abstract BACKGROUND: Matrix metalloproteinases (MMP) are important for cardiac remodeling. Recently microRNA (miR)-451a has been found to inhibit the expression of both MMP-2 and MMP-9 in human malignancies, but its role in cardiomyocytes is not explored. We hypothesized that miR-451a modulates MMP-2 and MMP-9 levels in human cardiomyocytes. METHODS: The role of miR-451a on regulation of MMP-2 and MMP-9 were evaluated in two separate pathological models using Cor.4U human inducible pluripotent stem cell-derived cardiomyocytes (hiPS-CMs): 1) endothelin-1 (ET-1) and 2) 48h hypoxia (1% O2). Both models wer...
Source: Am J Physiol Cell Ph... - October 16, 2019 Category: Cytology Authors: Scrimgeour NR, Wrobel A, Pinho MJ, Høydal MA Tags: Am J Physiol Cell Physiol Source Type: research

Bisphenol AF promotes inflammation in human white adipocytes.
Abstract Endocrine disrupting chemicals interact with transcription factors essential for adipocyte differentiation. Exposure to endocrine disrupting chemicals corresponds with elevated risks of obesity, but the effects of these compounds on human cells remain largely undefined. Widespread use of Bisphenol AF (BPAF) as a BPA alternative in the plastics industry presents unknown health risks. To this end, we discovered BPAF interferes with the metabolic function of mature human adipocytes. Although four-day exposures to BPAF accelerated adipocyte differentiation, we observed no effect on mature fat cell marker gene...
Source: Am J Physiol Cell Ph... - October 9, 2019 Category: Cytology Authors: Chernis N, Masschelin P, Cox AR, Hartig SM Tags: Am J Physiol Cell Physiol Source Type: research

Phosphorylation of eIF4E is dispensable for skeletal muscle hypertrophy.
Abstract The eukaryotic initiation factor 4E (eIF4E) is a major mRNA cap-binding protein that has a central role in translation initiation. Serine 209 (Ser209) is the single phosphorylation site within eIF4E and modulates its activity in response to MAPK pathway activation. Previous studies have reported that phosphorylation of eIF4E Ser209 promotes translation of key mRNAs such as cyclin D1 that regulate ribosome biogenesis. We hypothesized that phosphorylation of Ser209 is required for skeletal muscle growth in response to a hypertrophic stimulus by promoting ribosome biogenesis. To test this hypothesis, wild-ty...
Source: Am J Physiol Cell Ph... - October 9, 2019 Category: Cytology Authors: Figueiredo VC, Englund DA, Vechetti IJ, Alimov A, Peterson CA, McCarthy JJ Tags: Am J Physiol Cell Physiol Source Type: research

Peroxisome turnover and diurnal modulation of antioxidant activity in retinal pigment epithelia utilizes microtubule-associated protein 1 light chain 3B.
Abstract The retinal pigment epithelium (RPE) supports the outer retina through essential roles in the retinoid cycle, nutrient supply, ion exchange and waste removal. Each day the RPE removes the oldest ~10% of photoreceptor outer segment (OS) disk membranes through phagocytic uptake, which peaks following light onset. Impaired degradation of phagocytosed OS material by the RPE can lead to toxic accumulation of lipids, oxidative tissue damage, inflammation and cell death. OSs are rich in very long chain fatty acids which are preferentially catabolized in peroxisomes. Despite the importance of lipid degradation in...
Source: Am J Physiol Cell Ph... - October 2, 2019 Category: Cytology Authors: Daniele LL, Caughey J, Volland S, Sharp RC, Dhingra A, Williams DS, Philp NJ, Boesze-Battaglia K Tags: Am J Physiol Cell Physiol Source Type: research

Abnormal fertility, acrosome formation, IFT20 expression and localization in the conditional Gmap210 knockout mice.
Abstract GMAP210 is a cis-Golgi network-associated protein and Golgi membrane receptor for IFT20, intraflagellar transport component essential for male fertility and spermiogenesis in mice. To investigate the role of GMAP210 in male fertility and spermatogenesis, floxed Gmap210 mice were bred with Stra8-iCre mice so that Gmap210 is disrupted in spermatocytes and spermatids in this study. The Gmap210flox/flox: Stra8-iCre mutant mice showed no gross abnormalities and survived to adulthood. In adult males, testis and body weights showed no difference between controls and mutant mice. Low magnification histological ex...
Source: Am J Physiol Cell Ph... - October 2, 2019 Category: Cytology Authors: Wang Z, Shi Y, Ma S, Huang Q, Yap YT, Shi L, Zhang S, Zhou T, Li W, Hu B, Zhang L, Krawetz SA, Pazour GJ, Hess RA, Zhang Z Tags: Am J Physiol Cell Physiol Source Type: research

Cardiomyocyte functional screening - interrogating comparative electrophysiology of high-throughput model cell systems.
Abstract Cardiac arrhythmias of both atrial and ventricular origin are an important feature of cardiovascular disease. Novel anti-arrhythmic therapies are required to overcome current drug limitations related to effectiveness and pro-arrhythmia risk in some contexts. Cardiomyocyte culture models provide a high-throughput platform forscreening anti-arrhythmic compounds, but comparative information about electrophysiological properties of commonly used types of cardiomyocyte preparations is lacking.Standardization of cultured cardiomyocyte microelectrode array (MEA) experimentation is required for its application as...
Source: Am J Physiol Cell Ph... - October 2, 2019 Category: Cytology Authors: Wells SP, Waddell HM, Sim CB, Lim SY, Bernasochi GB, Pavlovic D, Kirchhof P, Porrello ER, Delbridge LMD, Bell JR Tags: Am J Physiol Cell Physiol Source Type: research

Extracellular pH and Intracellular Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) Control Cl- Currents in Guinea Pig Detrusor Smooth Muscle Cells.
Abstract Cl- channels serve as key regulators of smooth muscle excitability and contractility in vascular, intestinal, and airway cells. We recently reported Cl- conductance in detrusor smooth muscle (DSM) cells. Here, we used the whole-cell patch-clamp technique to further characterize biophysical properties and physiological regulators of Cl- currents in freshly-isolated Guinea pig DSM cells. The Cl- current demonstrated outward rectification arising from voltage-dependent gating of Cl- channels rather than the Cl‑ transmembrane gradient. An exposure of DSM cells to hypotonic extracellular solution (Δ 16...
Source: Am J Physiol Cell Ph... - October 2, 2019 Category: Cytology Authors: Yarotskyy V, Malysz J, Petkov GV Tags: Am J Physiol Cell Physiol Source Type: research

Primary cilia respond to intermittent low-magnitude high-frequency vibration and mediate vibration-induced effects in osteoblasts.
Conclusion: We showed that LMHFV induces morphological changes in primary cilia that may fine-tune their mechano-sensitivity. In addition, we demonstrated the significant inhibition by CH of LMHFV-induced OB mineralization, maturation, and differentiation, which might reveal the critical role of primary cilia in the process. PMID: 31577514 [PubMed - as supplied by publisher] (Source: Am J Physiol Cell Ph...)
Source: Am J Physiol Cell Ph... - October 2, 2019 Category: Cytology Authors: Li YH, Zhu D, Cao Z, Liu Y, Sun J, Tan L Tags: Am J Physiol Cell Physiol Source Type: research

Novel Interaction of Antioxidant-1 with TRAF4: Role in Inflammatory Responses in Endothelial Cells.
We reported that in proinflammatory cytokine TNFa-stimulated endothelial cells (ECs), cytosolic Cu chaperone Atox1 functions as a Cu-dependent transcription factor for NOX organizer p47phox, thereby increasing ROS-dependent inflammatory gene expression. However, the role and mechanism of Atox1 nuclear translocation in inflamed ECs remain unclear. Using enface staining and nuclear fractionation, here we show that Atox1 was localized in the nucleus in inflamed aortas from ApoE-/- mice with Angiotensin II infusion on a high fat diet, while it was found in cytosol in those from control mice. In cultured human ECs, TNFα s...
Source: Am J Physiol Cell Ph... - September 25, 2019 Category: Cytology Authors: Das A, Sudhahar V, Ushio-Fukai M, Fukai T Tags: Am J Physiol Cell Physiol Source Type: research

Force generated by myosin cross-bridges is reduced in myofibrils exposed to ROS/RNS.
In this study, we examined the effects of peroxynitrite (ONOO-) on the contractile properties of individual skeletal muscle myofibrils by monitoring myofibril-induced displacements of an atomic force cantilever upon activation and relaxation. The isometric force decreased by approximately 50% in myofibrils treated with the ONOO-donor (SIN-1) or directly with ONOO-, which was independent of the cross-bridge abundancy condition (i.e. rigor or relaxing condition) during SIN-1 or ONOO-treatment. The force decrease was attributed to an increase in the cross-bridge detachment rate (gapp) in combination with a conservation of the...
Source: Am J Physiol Cell Ph... - September 25, 2019 Category: Cytology Authors: Persson M, Steinz MM, Westerblad H, Lanner JT, Rassier DE Tags: Am J Physiol Cell Physiol Source Type: research

Knockout of the neonatal Fc Receptor (FcRn) in cultured podocytes alters IL-6 signaling and the actin cytoskeleton.
This study shows that in podocytes, FcRn modulates the IL-6 mediated response to proinflammatory stimuli and regulates podocytes actin structure, motility and synaptopodin expression. PMID: 31553647 [PubMed - as supplied by publisher] (Source: Am J Physiol Cell Ph...)
Source: Am J Physiol Cell Ph... - September 25, 2019 Category: Cytology Authors: Tonsawan P, Dylewski J, Lewis L, Blaine J Tags: Am J Physiol Cell Physiol Source Type: research

Palmitic acid induces guanylin gene expression through the toll-like receptor 4/nuclear factor κB pathway in rat macrophages.
Palmitic acid induces guanylin gene expression through the toll-like receptor 4/nuclear factor κB pathway in rat macrophages. Am J Physiol Cell Physiol. 2019 Sep 25;: Authors: Akieda-Asai S, Ma H, Date Y Abstract Recently, we showed that double-transgenic rats overexpressing guanylin (Gn), a bioactive peptide, and its receptor, guanylyl cyclase-C (GC-C), specifically in macrophages demonstrate an anti-obesity phenotype and low expression levels of proinflammatory cytokines in the mesenteric fat even when fed a high-fat diet.Here, we examined the levels and mechanism of Gn and GC-C transcription ...
Source: Am J Physiol Cell Ph... - September 25, 2019 Category: Cytology Authors: Akieda-Asai S, Ma H, Date Y Tags: Am J Physiol Cell Physiol Source Type: research

Identification of a Novel Selective and Potent Inhibitor of Glycogen Synthase Kinase-3.
Abstract Glycogen synthase kinase-3 (GSK-3) is a multi-tasking protein kinase that regulates numerous critical cellular functions. Not surprisingly, elevated GSK-3 activity has been implicated in a host of diseases including pathological inflammation, diabetes, cancer, arthritis, asthma, bipolar disorder, and Alzheimer's. Therefore, reagents that inhibit GSK-3 activity provide a means to investigate the role of GSK-3 in cellular physiology and pathophysiology and could become valuable therapeutics. Finding a potent inhibitor of GSK-3 that can selectively target this kinase, amongst over 500 protein kinases in the ...
Source: Am J Physiol Cell Ph... - September 25, 2019 Category: Cytology Authors: Noori MS, Bhatt PM, Courreges MC, Ghazanfari D, Cuckler C, Orac CM, McMills MC, Schwartz FL, Deosarkar SP, Bergmeier SC, McCall KD, Goetz DJ Tags: Am J Physiol Cell Physiol Source Type: research

Electrical stimulation prevents doxorubicin-induced atrophy and mitochondrial loss in cultured myotubes.
Abstract Muscle contraction may protect against the effects of chemotherapy to cause skeletal muscle atrophy, but the mechanisms underlying these benefits are unclear. To address this question, we utilized in vitro modeling of contraction and mechanotransduction in C2C12 myotubes treated with doxorubicin (DOX; 0.2 μM for 3 days). Myotubes expressed contractile proteins and organized these into functional myofilaments, as electrical field stimulation (STIM) induced intracellular calcium (Ca2+) transients and contractions, both of which were prevented by inhibition of membrane depolarization. DOX treatment reduce...
Source: Am J Physiol Cell Ph... - September 18, 2019 Category: Cytology Authors: Guigni BA, Fix DK, Bivona JJ, Palmer BM, Carson JA, Toth MJ Tags: Am J Physiol Cell Physiol Source Type: research

A myosin-based mechanism for stretch activation and its possible role revealed by varying phosphate concentration in fast and slow mouse skeletal muscle fibers.
Abstract Stretch activation (SA) is a delayed increase in force following a rapid muscle length increase. SA is best known for its role in asynchronous insect flight muscle where it has replaced calcium's typical role of modulating muscle force levels during a contraction cycle. SA also occurs in mammalian skeletal muscle, but has previously been thought to be too low in magnitude, relative to calcium-activated (CA) force, to be a significant contributor to force generation during locomotion. To test this supposition, we compared SA and CA force at different Pi concentrations (0-16 mM) in skinned mouse soleus (slow-...
Source: Am J Physiol Cell Ph... - September 18, 2019 Category: Cytology Authors: Straight CR, Bell KM, Slosberg JN, Miller MS, Swank DM Tags: Am J Physiol Cell Physiol Source Type: research

DUSP1 regulates cell cycle progression and apoptosis in cumulus cells by affecting mitochondrial function, oxidative stress, and autophagy.
In this study, we explored the effects of DUSP1 expression inhibition on cell cycle progression, proliferation, apoptosis, and lactate and cholesterol levels in cumulus cells and examined reactive oxygen species levels, mitochondrial function, autophagy, and the expression of key cytokine genes. The results showed that inhibition of DUSP1 in cumulus cells caused abnormal cell cycle progression, increased cell proliferation, decreased apoptosis rates, increased cholesterol synthesis and lactic acid content, and increased cell expansion. The main reason for these effects was that inhibition of DUSP1 reduced ROS accumulation,...
Source: Am J Physiol Cell Ph... - September 18, 2019 Category: Cytology Authors: Fu XH, Chen CZ, Li S, Han DX, Wang YJ, Yuan B, Gao Y, Zhang JB, Jiang H Tags: Am J Physiol Cell Physiol Source Type: research

AJP-Cell Physiology begins a Theme on "Cellular Processes in Tumour Metastasis - From Basic Research to Translation".
AJP-Cell Physiology begins a Theme on "Cellular Processes in Tumour Metastasis - From Basic Research to Translation". Am J Physiol Cell Physiol. 2019 Sep 18;: Authors: Chevet E PMID: 31532717 [PubMed - as supplied by publisher] (Source: Am J Physiol Cell Ph...)
Source: Am J Physiol Cell Ph... - September 18, 2019 Category: Cytology Authors: Chevet E Tags: Am J Physiol Cell Physiol Source Type: research

Cellular and Extracellular Matrix of bone, with Principals of Synthesis and Dependency of Mineral Deposition on Cell Membrane Transport.
Abstract Bone differs from other connective tissues; it is isolated by a layer of osteoblasts that are connected by tight and gap junctions. This allows bone to create dense lamellar type I collagen, control pH, mineral deposition, and regulate water content forming a compact and strong structure. New woven bone formed after degradation of mineralized cartilage is rapidly degraded and re-synthesized to impart structural order for local bone strength. Ossification is regulated by thickness of bone units and by patterning via bone morphogenetic receptors. This superfamily interacts with receptors for additional sign...
Source: Am J Physiol Cell Ph... - September 18, 2019 Category: Cytology Authors: Schlesinger PH, Blair HC, Beer Stolz D, Riazanski V, Ray EC, Tourkova IL, Nelson DJ Tags: Am J Physiol Cell Physiol Source Type: research

Burn-Induced Reductions in Mitochondrial Abundance and Efficiency are More Pronounced with Small Volumes of Colloids in Swine.
Abstract Severe burn injury results in systemic disruption of metabolic regulations and impaired cardiac function. Restoration of hemodynamic homeostasis utilizing intravenous (IV) fluids is critical for acute care of the burn victim. However, the effects of burns and resuscitation on cardiomyocyte mitochondria arecurrently unknown. The purpose of this study is to determine cardiac mitochondrial function in a swine burn model with subsequent resuscitation using either crystalloids or colloids. Anesthetized Yorkshire swine (n=23) sustained 40% total body surface area (TBSA) burns and received IV crystalloids (n=11)...
Source: Am J Physiol Cell Ph... - September 18, 2019 Category: Cytology Authors: Chao T, Gomez BI, Heard TC, Smith BW, Dubick MA, Burmeister DM Tags: Am J Physiol Cell Physiol Source Type: research

Slc26a6 is an apical membrane anion exchanger that drives HCO3--dependent fluid secretion in murine pancreatic acinar cells.
In this study, Slc26a6 null mice were used to explore the function of Slc26a6 in the exocrine pancreas. Slc26a6 primarily localized to the apical membrane of pancreatic exocrine acinar cells. The volume of stimulated juice secretion by the ex vivo pancreas was significantly reduced approximately 35% in Slc26a6-/- mice, but no changes occurred in the gross structure or gland weights of Slc26a6 null mice. The secretion of pancreatic juice by Slc26a6+/+ mice was dependent on HCO3-, while in contrast, fluid secretion by Slc26a6-/- mice was independent of HCO3- suggesting that Slc26a6 mediates the HCO3--dependent component of f...
Source: Am J Physiol Cell Ph... - September 18, 2019 Category: Cytology Authors: Munemasa T, Mukaibo T, Melvin JE Tags: Am J Physiol Cell Physiol Source Type: research

Selenoprotein W Deficiency Does Not Affect Oxidative Stress and Insulin Sensitivity in the Skeletal Muscle of High-fat Diet-fed Obese Mice.
Abstract Selenoprotein W (SelW) is a selenium containing protein with a redox motif found abundantly in the skeletal muscle of rodents. Previous in vitro studies suggest that SelW plays an antioxidant role; however, relatively few in vivo studies have addressed the antioxidant role of SelW. Since oxidative stress is a causative factor for the development of insulin resistance in obese subjects, we hypothesized that if SelW plays a role as an antioxidant, SelW deficiency could aggravate the oxidative stress and insulin resistance caused by a high-fat diet. SelW deficiency did not affect insulin sensitivity and H2O2...
Source: Am J Physiol Cell Ph... - September 11, 2019 Category: Cytology Authors: Shin MG, Cha HN, Park S, Kim YW, Kim JY, Park SY Tags: Am J Physiol Cell Physiol Source Type: research

Hemoglobin Alters Vitamin Carrier Uptake and Vitamin D Metabolism in Proximal Tubule Cells: Implications for Sickle Cell Disease.
Abstract Kidney disease, including proximal tubule (PT) dysfunction, and vitamin D deficiency are among the most prevalent complications in sickle cell disease (SCD) patients. Although these two comorbidities have never been linked in SCD, the PT is the primary site for activation of vitamin D. Precursor 25(OH)D bound to vitamin D binding protein (DBP) is taken up by PT cells via megalin/cubilin receptors, hydroxylated to the active 1,25(OH)2D form, and released into the bloodstream. We tested the hypothesis that cell-free hemoglobin (Hb) filtered into the PT lumen impairs vitamin D uptake and metabolism. Hb at co...
Source: Am J Physiol Cell Ph... - September 11, 2019 Category: Cytology Authors: Gliozzi ML, Rbaibi Y, Long KR, Vitturi DA, Weisz OA Tags: Am J Physiol Cell Physiol Source Type: research

Statin administration activates System Xc- in skeletal muscle: a potential mechanism explaining statin-induced muscle pain.
Abstract Statins are a cholesterol-lowering drug class that significantly reduce cardiovascular disease risk. Despite their safety and effectiveness, musculoskeletal side-effects, particularly myalgia, are prominent and the most common reason for discontinuance. The cause of statin-induced myalgia is unknown, so defining the underlying mechanism(s) and potential therapeutic strategies is of clinical importance. Here we tested the hypothesis that statin administration activates skeletal muscle system xC-, a cystine/glutamate antiporter, to increase intracellular cysteine and therefore glutathione synthesis to atten...
Source: Am J Physiol Cell Ph... - September 11, 2019 Category: Cytology Authors: Rebalka IA, Cao AW, May L, Tarnopolsky MA, Hawke TJ Tags: Am J Physiol Cell Physiol Source Type: research

cGMP-dependent protein kinase II determines beta-catenin accumulation essential for uterine decidualization in mice.
In this study, we show that Prkg2 has a gradually increased expression pattern during peri-implantation and artificial decidualization, and the expression of Prkg2 is induced by estrogen and progesterone in the ovariectomized mouse uteri and primary cultured uterine stromal cells, the process of which is blocked by treating with estrogen receptor (ER) antagonist (ICI 182,780) and progesterone receptor (PR) antagonist (RU486). Inhibition of Prkg2 activity by HA-100 promotes uterine stromal cell proliferation but compromises decidualization with decreased expression of Prl8a2. In addition, the functional regulation of decidu...
Source: Am J Physiol Cell Ph... - September 11, 2019 Category: Cytology Authors: Zhang Y, Yan L, Liu J, Cui S, Qiu J Tags: Am J Physiol Cell Physiol Source Type: research

Decreased SLC26A3 Expression and Function in Intestinal Epithelial Cells in Response to Cryptosporidiium parvum Infection.
Abstract The protozoan parasite Cryptosporidium parvum (CP) causes cryptosporidiosis, a diarrheal disease worldwide. Infection in immunocompetent hosts typically results in acute, self-limiting or recurrent diarrhea. However, in immunocompromized individuals infection can cause fulminant diarrhea, extraintestinal manifestations, and death. To date, the mechanisms underlying CP-induced diarrheal pathogenesis are poorly understood. Diarrheal diseases most commonly involve increased secretion and/or decreased absorption of fluid and electrolytes. We and others have previously shown impaired chloride absorption in inf...
Source: Am J Physiol Cell Ph... - September 4, 2019 Category: Cytology Authors: Kumar A, Jayawardena D, Anbazhagan AN, Chatterjee I, Priyamvada S, Alrefai WA, Borthakur A, Dudeja PK Tags: Am J Physiol Cell Physiol Source Type: research

The fatty acid derivative palmitoylcarnitine abrogates colorectal cancer cell survival by depleting glutathione.
Abstract Previous evidence suggests that palmitoylcarnitine incubations trigger mitochondrial-mediated apoptosis in HT29 colorectal adenocarcinoma cells, yet non-transformed cells appear resistant. The mechanism by which palmitoylcarnitine induces cancer cell death is unclear. The purpose of this investigation was to examine the relationship between mitochondrial kinetics and glutathione buffering in determining the effect of palmitoylcarnitine on cell survival. HT29 and HCT 116 colorectal adenocarcinoma cells, CCD 841 non-transformed colon cells and MCF7 breast adenocarcinoma cells were exposed to 0μM, 50μM...
Source: Am J Physiol Cell Ph... - September 4, 2019 Category: Cytology Authors: Turnbull PC, Hughes MC, Perry CGR Tags: Am J Physiol Cell Physiol Source Type: research

Pyridoxine and pancreatic acinar cells: transport physiology and effect on gene expression profile.
Abstract Pyridoxine (vitamin B6), an essential micronutrient for normal cell physiology, plays an important role in the function of the exocrine pancreas. Pancreatic acinar cells (PACs) obtain vitamin B6 from circulation, but little is known about the mechanism involved in the uptake process; limited information also exists on the effect of pyridoxine availability on the gene expression profile in these cells. We addressed both these issues in the current investigation using mouse-derived pancreatic acinar 266-6 cells (PAC 266-6) and human primary PACs (hPACs; obtained from organ donors), together with appropriate...
Source: Am J Physiol Cell Ph... - September 4, 2019 Category: Cytology Authors: Srinivasan P, Ramesh V, Wu J, Heskett CW, Chu BD, Said HM Tags: Am J Physiol Cell Physiol Source Type: research

Clinical values of non-coding RNAs in cardiovascular, pulmonary, and muscle diseases.
Abstract While a majority of the mammalian genome is transcribed to RNA, mounting evidence indicates that only a minor proportion of these transcriptional products are actually translated into proteins. Since the discovery of the first non-coding RNA (ncRNA) in the 1980s, the field has gone on to recognize ncRNAs as important molecular regulators of RNA activity and protein function-knowledge of which has stimulated the expansion of a scientific field that quests to understand the role of ncRNAs in cellular physiology, tissue homeostasis, and human disease. Although our knowledge of these molecules has significant...
Source: Am J Physiol Cell Ph... - September 4, 2019 Category: Cytology Authors: Bonnet S, Boucherat O, Paulin R, Wu D, Hindmarch CCT, Archer SL, Song R, Moore JB, Provencher S, Zhang L, Uchida S Tags: Am J Physiol Cell Physiol Source Type: research

Contribution of Transcription Factor EB to AdipoRon-induced Inhibition of Arterial Smooth Muscle Cell Proliferation and Migration.
This study provides novel mechanistic insights into understanding the therapeutic effects of adipoRon on TFEB signaling and pathological vascular remodeling. PMID: 31483704 [PubMed - as supplied by publisher] (Source: Am J Physiol Cell Ph...)
Source: Am J Physiol Cell Ph... - September 4, 2019 Category: Cytology Authors: Wang YT, Chen J, Li X, Umetani M, Chen Y, Li PL, Zhang Y Tags: Am J Physiol Cell Physiol Source Type: research

Letter to the editor: Cross-contaminated cell lines: there is no time to lose.
PMID: 31483148 [PubMed - in process] (Source: Am J Physiol Cell Ph...)
Source: Am J Physiol Cell Ph... - September 1, 2019 Category: Cytology Authors: Rojas A, Gonzalez I Tags: Am J Physiol Cell Physiol Source Type: research

Molecular regulation of human skeletal muscle protein synthesis in response to exercise and nutrients: a compass for overcoming age-related anabolic resistance.
MOLECULAR REGULATION OF HUMAN SKELETAL MUSCLE PROTEIN SYNTHESIS IN RESPONSE TO EXERCISE AND NUTRIENTS: A COMPASS FOR OVERCOMING AGE-RELATED ANABOLIC RESISTANCE. Am J Physiol Cell Physiol. 2019 Aug 28;: Authors: Hodson N, West DWD, Philp A, Burd NA, Moore DR Abstract Skeletal muscle mass, a strong predictor of longevity and health in humans, is determined by the balance of two cellular processes, muscle protein synthesis (MPS) and muscle protein breakdown (MPB). Of these two, MPS seems to be particularly sensitive to changes in mechanical load and/or nutritional status, and therefore much research has ...
Source: Am J Physiol Cell Ph... - August 28, 2019 Category: Cytology Authors: Hodson N, West DWD, Philp A, Burd NA, Moore DR Tags: Am J Physiol Cell Physiol Source Type: research

Cell type- and tissue-specific functions of ecto-5'-nucleotidase (CD73).
Abstract CD73 is a ubiquitously-expressed glycosylphosphatidylinositol (GPI)-anchored glycoprotein that converts extracellular adenosine 5'-monophosphate (AMP) to adenosine. Anti-CD73 inhibitory antibodies are currently undergoing clinical testing for cancer immunotherapy. However, CD73 has many protective physiological functions that need to be taken into account for new targeted therapies. This review covers CD73 functions in multiple organ systems and cell types, with a particular focus on novel findings from the last 5 years. Missense loss-of-function mutations in the CD73-encoding gene (NT5E) cause the rare d...
Source: Am J Physiol Cell Ph... - August 28, 2019 Category: Cytology Authors: Minor M, Alcedo KP, Battaglia RA, Snider NT Tags: Am J Physiol Cell Physiol Source Type: research

Identification of the intermediate filament protein synemin/SYNM as a target of myocardin family coactivators.
, Rippe C Abstract Myocardin (MYOCD) is a critical regulator of smooth muscle cell (SMC) differentiation, but its transcriptional targets remain to be exhaustively characterized, especially at the protein level. Here we used a bioinformatics approach to identify novel potential MYOCD targets, and we confirm several at the protein level, including SORBS1, SLMAP, SYNM, and MCAM. We focused on SYNM, which encodes the intermediate filament protein synemin. SYNM rivalled smooth muscle myosin (MYH11) for SMC specificity, and was controlled at the mRNA and protein levels by all myocardin-related transcription factors (MR...
Source: Am J Physiol Cell Ph... - August 28, 2019 Category: Cytology Authors: Swärd K, Krawczyk KK, Morén B, Zhu B, Matic L, Holmberg J, Hedin U, Uvelius B, Stenkula K, Rippe C Tags: Am J Physiol Cell Physiol Source Type: research

Acute inhibition of protein deacetylases does not impact skeletal muscle insulin action.
CONCLUSIONS: Acutely reducing the deacetylase activity of HDACs and/or sirtuins does not impact insulin action in skeletal muscle. PMID: 31461343 [PubMed - as supplied by publisher] (Source: Am J Physiol Cell Ph...)
Source: Am J Physiol Cell Ph... - August 28, 2019 Category: Cytology Authors: Martins VF, Begur M, Lakkaraju S, Svensson K, Park J, Hetrick B, McCurdy CE, Schenk S Tags: Am J Physiol Cell Physiol Source Type: research

Molecular Mechanism of TMEM16A Regulation: Role of CaMKII and PP1/PP2A.
This study explored the mechanism by which Ca2+-activated Cl-channels (CaCC) encoded by the Tmem16agene are regulated by CaMKII and protein phosphatases 1 (PP1) and 2A (PP2A). Ca2+-activated Cl-currents (IClCa) were recorded from HEK-293 cells expressing mouse TMEM16A. IClCawere evoked using a pipette solution in which free Ca2+concentration ([Ca2+]i) was clamped to 500 nM, in the presence (5 mM) or absence of ATP. With 5 mM ATP, IClCadecayed to below 50% of the initial current magnitude within 10 min after seal rupture. IClCarundown seen with ATP-containing pipette solution was greatly diminished by omitting ATP. IClCarec...
Source: Am J Physiol Cell Ph... - August 28, 2019 Category: Cytology Authors: Ayon RJ, Hawn MB, Aoun J, Wiwchar M, Forrest AS, Cunningham F, Singer CA, Valencik ML, Greenwood IA, Leblanc N Tags: Am J Physiol Cell Physiol Source Type: research

GABA receptors differentially regulate lifespan and healthspan in C. elegans through distinct downstream mechanisms.
Abstract GABA, a prominent inhibitory neurotransmitter, is best known to regulate neuronal functions in the nervous system. However, much less is known about the role of GABA signaling in other physiological processes. Interestingly, recent work showed that GABA signaling can regulate lifespan via a metabotropic GABAB receptor in C. elegans. However, the role of other types of GABA receptors in lifespan has not been clearly defined. It is also unclear whether GABA signaling regulates healthspan. Here, using C. elegans as a model, we systematically interrogated the role of various GABA receptors in both lifespan an...
Source: Am J Physiol Cell Ph... - August 21, 2019 Category: Cytology Authors: Yuan F, Zhou J, Xu L, Jia W, Chun L, Xu XS, Liu J Tags: Am J Physiol Cell Physiol Source Type: research

The Impact of Skeletal Muscle Contraction on CD146+Lin- Pericytes.
Abstract Unaccustomed resistance exercise can initiate skeletal muscle remodeling and adaptive mechanisms that can confer protection from damage and enhanced strength with subsequent stimulation. The myofiber may provide the primary origin for adaptation, yet multiple mononuclear cell types within the surrounding connective tissue may also contribute. The purpose of this study was to evaluate the acute response of muscle-resident interstitial cells to contraction initiated by electrical stimulation (e-stim), and subsequently determine the contribution of pericytes to remodeling as a result of training. Mice were s...
Source: Am J Physiol Cell Ph... - August 21, 2019 Category: Cytology Authors: Dvoretskiy S, Garg K, Munroe M, Pincu Y, Mahmassani ZS, Coombs C, Blackwell B, Garcia G, Waterstradt G, Lee I, Drnevich J, Rhodes JS, Boppart MD Tags: Am J Physiol Cell Physiol Source Type: research