Oroxylin A induces apoptosis of activated hepatic stellate cells through endoplasmic reticulum stress
In conclusion, our findings suggest a role for ERS in the mechanism underlying amelioration of hepatic fibrosis by OA. (Source: Apoptosis)
Source: Apoptosis - September 19, 2019 Category: Molecular Biology Source Type: research
Defining the role of cytoskeletal components in the formation of apoptopodia and apoptotic bodies during apoptosis
AbstractDuring apoptosis, dying cells undergo dynamic morphological changes that ultimately lead to their disassembly into fragments called apoptotic bodies (ApoBDs). Reorganisation of the cytoskeletal structures is key in driving various apoptotic morphologies, including the loss of cell adhesion and membrane bleb formation. However, whether cytoskeletal components are also involved in morphological changes that occur later during apoptosis, such as the recently described generation of thin apoptotic membrane protrusions called apoptopodia and subsequent ApoBD formation, is not well defined. Through monitoring the progres...
Source: Apoptosis - September 4, 2019 Category: Molecular Biology Source Type: research
Rotenone protects against β-cell apoptosis and attenuates type 1 diabetes mellitus
AbstractType 1 diabetes mellitus (T1DM) is caused by pancreatic β-cell dysfunction and apoptosis, with consequent severe insulin deficiency. Thus, β-cell protection may be a primary target in the treatment of T1DM. Evidence has demonstrated that defective mitochondrial function plays an important role in pancreatic β-cell dysfunction and apoptosis; however, t he fundamental effect of mitochondrial complex I action on β-cells and T1DM remains unclear. In the current study, the pancreas protective effect of complex I inhibitor rotenone (ROT) and its potential mechanism were assessed in a streptozotocin (S...
Source: Apoptosis - September 3, 2019 Category: Molecular Biology Source Type: research
Combination of ERK2 inhibitor VX-11e and voreloxin synergistically enhances anti-proliferative and pro-apoptotic effects in leukemia cells
In conclusion, combination of VX-11e and voreloxin can exert a synergistic anticancer effect in leukemia cells. (Source: Apoptosis)
Source: Apoptosis - September 2, 2019 Category: Molecular Biology Source Type: research
TNF- α-elicited miR-29b potentiates resistance to apoptosis in peripheral blood monocytes from patients with rheumatoid arthritis
AbstractCD14-positive monocytes from patients with rheumatoid arthritis (RA) are more resistant to apoptosis, which promotes their persistence at the inflammatory site and thereby contributes crucially to immunopathology. We sought to elucidate one mechanism underlying this unique pathogenesis: resistance to apoptosis and the potential involvement of miR-29b in this process. CD14-positive peripheral blood monocytes (PBMs) from RA patients were observed to be resistant to spontaneous apoptosis compared to PBMs from healthy volunteers. Intriguingly, expression of miR-29b was significantly upregulated in PBMs from RA patients...
Source: Apoptosis - August 30, 2019 Category: Molecular Biology Source Type: research
Correction to: SPECT/CT imaging of apoptosis in aortic aneurysm with radiolabeled duramycin
The original version of this article unfortunately contains errors in Figure 4. An incorrect Figure 4D is published which is actually a repetition of Figure 2C (i.e., apoptosis rate in control vs. H2O2-treated group). The correct Figure 4D should be the aortic diameter of control vs. experimental groups. Also, the order of part figures (a\b\c\d) in Figure 4E is incorrect. The correct Figure 4 is given below. (Source: Apoptosis)
Source: Apoptosis - August 16, 2019 Category: Molecular Biology Source Type: research
Autophagy protects HUVECs against ER stress-mediated apoptosis under simulated microgravity
AbstractAstronauts exposed to a gravity-free environment experience cardiovascular deconditioning that causes post-spaceflight orthostatic intolerance and other pathological conditions. Endothelial dysfunction is an important factor responsible for this alteration. Our previous study showed enhanced autophagy in endothelial cells under simulated microgravity. The present study explored the cytoprotective role of autophagy under microgravity in human umbilical vein endothelial cells (HUVECs). We found that clinorotation for 48 h induced apoptosis and endoplasmic reticulum (ER) stress in HUVECs. ER stress and the ...
Source: Apoptosis - July 28, 2019 Category: Molecular Biology Source Type: research
MAGI1 mediates tumor metastasis through c-Myb/miR-520h/MAGI1 signaling pathway in renal cell carcinoma
In this study, we demonstrated that MAGI1 was markedly decreased in the RCC and indicated poor survival. Furthermore, we found that MAGI1 suppressed the invasion and migration of human RCC cells. Mechanistic investigations revealed that MAGI1 stabilized the PTEN/MAGI1/ β-catenin complex to inhibit β-catenin signaling pathway. Moreover, MAGI1 was targeted by miR-520h which was transcriptionally activated by c-Myb. Collectively, our findings suggested that MAGI1mediated tumor metastasis through c-Myb/miR-520h/MAGI1 signaling pathway in RCC. (Source: Apoptosis)
Source: Apoptosis - July 26, 2019 Category: Molecular Biology Source Type: research
Deubiquitylatinase inhibitor b-AP15 induces c-Myc-Noxa-mediated apoptosis in esophageal squamous cell carcinoma
AbstractEsophageal squamous cell carcinoma (ESCC) is one of the most malignant tumors in east Asia. However, the molecular mechanism underlying its progression remains unclear. The ubiquitin –proteasome system (UPS) is a central mechanism for protein degradation and turnover. Accumulating evidence showed that more and more deubiquitinases could serve as attractive anti-cancer target. The expression of USP14 and UCH37 in esophagus squamous cell carcinoma tissues were examined by immuno histochemistry and western blot assays. Effect of b-AP15, a USP14 and UCH37 inhibitor, on ESCC cell growth was evaluated by cell viabi...
Source: Apoptosis - July 23, 2019 Category: Molecular Biology Source Type: research
Inhibition of SIRT1/2 upregulates HSPA5 acetylation and induces pro-survival autophagy via ATF4-DDIT4-mTORC1 axis in human lung cancer cells
AbstractSirtuins have emerged as a promising novel class of anti-cancer drug targets. Inhibition of SIRT1 and SIRT2 induces apoptosis in cancer cells and they play multifaceted roles in regulating autophagy. In the present study, we found that salermide, a SIRT1/2-specific inhibitor or small interfering RNAs (siRNAs) to block SIRT1/2 expression could induce autophagy in human NSCLC cells. Moreover, SIRT1/2 inhibition increased the expression levels of ATF4 and DDIT4 and downregulated p-RPS6KB1 and p-EIF4EBP1, two downstream molecules of mTORC1. Moreover, ATF4 or DDIT4 knockdown attenuated salermide-induced autophagy, sugge...
Source: Apoptosis - July 17, 2019 Category: Molecular Biology Source Type: research
Hyperosmotic stress promotes endoplasmic reticulum stress-dependent apoptosis in adult rat cardiac myocytes
AbstractIn different pathological situations, cardiac cells undergo hyperosmotic stress and cell shrinkage. This change in cellular volume has been associated with contractile dysfunction and cell death. However, the intracellular mechanisms involved in hyperosmotic stress-induced cell death have not been investigated in depth in adult cardiac myocytes. Given that osmotic stress has been shown to promote endoplasmic reticulum stress (ERS), a recognized trigger for apoptosis, we examined whether hyperosmotic stress triggers ERS in adult cardiac myocytes and if so whether this mechanism mediates hyperosmotic stress-induced c...
Source: Apoptosis - July 14, 2019 Category: Molecular Biology Source Type: research
Neuronal life or death linked to depression treatment: the interplay between drugs and their stress-related outcomes relate to single or combined drug therapies
In conclusion, our findings may pave the way to better understanding of the stress-related effects on neurons associated with mono- and combined therapy with antidepressants. (Source: Apoptosis)
Source: Apoptosis - July 4, 2019 Category: Molecular Biology Source Type: research
Apoptosis regulation in the penumbra after ischemic stroke: expression of pro- and antiapoptotic proteins
AbstractIschemic stroke is the leading cause of human disability and mortality in the world. The main problem in stroke therapy is the search of efficient neuroprotector capable to rescue neurons in the potentially salvageable transition zone (penumbra), which is expanding after brain damage. The data on molecular mechanisms of penumbra formation and expression of diverse signaling proteins in the penumbra during first 24 h after ischemic stroke are discussed. Two basic features of cell death regulation in the ischemic penumbra were observed: (1) both apoptotic and anti-apoptotic proteins are simultaneously over-expr...
Source: Apoptosis - June 28, 2019 Category: Molecular Biology Source Type: research
JNK inhibition blocks piperlongumine-induced cell death and transcriptional activation of heme oxygenase-1 in pancreatic cancer cells
AbstractPiperlongumine (PL) is an alkaloid that inhibits glutathioneS-transferase pi 1 (GSTP1) activity, resulting in elevated reactive oxygen species (ROS) levels and cancer-selective cell death. We aimed to identify stress-associated molecular responses to PL treatment in pancreatic ductal adenocarcinoma (PDAC) cells. GSTP1 directly interacts with JNK, which is activated by oxidative stress and can lead to decreased cancer cell proliferation and cell death. Therefore, we hypothesized that JNK pathways are activated in response to PL treatment. Our results show PL causes dissociation of GSTP1 from JNK; robust JNK, c-Jun, ...
Source: Apoptosis - June 25, 2019 Category: Molecular Biology Source Type: research
Aspirin induces oncosis in tumor cells
AbstractIn contrast to the well-known anti-tumor mechanisms of aspirin in inducing apoptosis or autophagy, we here for the first time report oncosis induced by aspirin in tumor cells. In vitro and in vivo analysis showed that aspirin induced compromised Bcl-XL level and subsequent ATP depletion. Overexpression of CFP-Bcl-XL in Hela and A549 cells observably inhibited aspirin-induced ATP depletion and almost completely inhibited the aspirin-induced cells bubbling, while pharmacological inhibition of endogenous Bcl-XL activity by ABT-737 remarkably promoted aspirin-induced ATP depletion and cells bubbling, suggesting the key...
Source: Apoptosis - June 25, 2019 Category: Molecular Biology Source Type: research
Fipronil induces apoptosis and cell cycle arrest in porcine oocytes during in vitro maturation
In conclusion, FPN induces apoptosis and cell cycle arrest in porcine oocyte maturation because of increased ROS levels and DNA damage. This suggests that the FPN in the environment may have potential detrimental effects on the female mammalian reproductive system. (Source: Apoptosis)
Source: Apoptosis - June 24, 2019 Category: Molecular Biology Source Type: research
SPECT/CT imaging of apoptosis in aortic aneurysm with radiolabeled duramycin
The objective of this research was to estimate whether a[99mTc]duramycin probe can be used for apoptosis imaging in patients with aortic aneurysm (AA). Vascular smooth muscle cell (SMC) apoptosis has an important influence on AA development. Thus, non-invasive imaging of SMC apoptosis may be able to evaluate AA progress and risk stratification. SMCs were treated with hydrogen peroxide (H2O2; 200 μΜ) or culture medium as a control. Apoptosis was measured using flow cytometry and[99mTc]duramycin to detect the binding efficiency to apoptotic SMCs. C57/BL6 mice were administered angiotensin-II and beta-aminopropion...
Source: Apoptosis - June 20, 2019 Category: Molecular Biology Source Type: research
CNOT3 contributes to cisplatin resistance in lung cancer through inhibiting RIPK3 expression
In this study, after screening theCNOT3 mRNA in a cancer microarray database called Oncomine and examining the expression levels ofCNOT3 mRNA in normal tissues and lung cancer tissues, we found thatCNOT3 was up-regulated in lung cancer tissues. Besides, its high-expression was associated with poor prognosis of lung cancer patients. We also found higher expression level of CNOT3 and lower expression level of receptor-interacting protein kinase 3 (RIPK3) in cisplatin-resistant A549 (A549/DDP) cells, and knocking down CNOT3 expression could sensitize A549/DDP cells to cisplatin-induced apoptosis. We demonstrated that CNOT3 de...
Source: Apoptosis - June 7, 2019 Category: Molecular Biology Source Type: research
ATP induces caspase-3/gasdermin E-mediated pyroptosis in NLRP3 pathway-blocked murine macrophages
In this study, we used cellular models to mimic such blockade of NLRP3 activation: bone marrow-derived macrophages (BMDMs) treated with NLRP3-specific inhibitor MCC950 and RAW264.7 cells deficient in ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) expression. The results showed that ATP treatment induced lytic cell death morphologically resembling canonical pyroptosis in both MCC950-treated BMDMs and RAW264.7 cells, but did not cause the activation of caspase-1 (by detecting caspase-1p10 and mature interleukin-1 β) and cleavage of GSDMD. Instead, both apoptotic initiator (caspase-...
Source: Apoptosis - June 6, 2019 Category: Molecular Biology Source Type: research
MicroRNA-3607 inhibits the tumorigenesis of colorectal cancer by targeting DDI2 and regulating the DNA damage repair pathway
In this study, we analyzed miR-3607 expression Pan-Cancer data from the NCI ’s Genomic Data Commons (GDC) and found that miR-3607 was downregulated in lymphatic invasion patients and in recurrent cancer and correlated with Pan-Cancer patient survival. Functional studies indicated that the overexpression of miR-3607 decreased CRC cell proliferation, migration and invasion. Additionally, we used gene set enrichment analysis (GSEA), Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and a protein–protein interaction network to demonstrate that miR-3607 affects the DDR...
Source: Apoptosis - May 26, 2019 Category: Molecular Biology Source Type: research
Berberine mitigates IL-21/IL-21R mediated autophagic influx in fibroblast-like synoviocytes and regulates Th17/Treg imbalance in rheumatoid arthritis
AbstractIn our previous study, we explored the therapeutic effect of berberine (BBR) against IL-21/IL-21R mediated inflammatory proliferation of adjuvant-induced arthritic fibroblast-like synoviocytes (AA-FLS) through the PI3K/Akt pathway. The current study was designed to explore the therapeutic potential of BBR (15 –45 µM) against IL-21/IL-21R mediated autophagy in AA-FLS mediated through PI3K/Akt signaling and Th17/Treg imbalance. Upon IL-21 stimulation, AA-FLS expressed elevated levels of autophagy-related 5 (Atg5), Beclin-1 and LC3-phosphatidylethanolamine conjugate 3-II (LC3-II) through the utilizati...
Source: Apoptosis - May 19, 2019 Category: Molecular Biology Source Type: research
Letter to the editor regarding article, “Role of glycogen synthase kinase following myocardial infarction and ischemia–reperfusion”
Source: Apoptosis - May 10, 2019 Category: Molecular Biology Source Type: research
Endothelin-1-mediated cerebral ischemia in mice: early cellular events and the role of caspase-3
AbstractOver the past 30 years a number of animal models of cerebral ischemic injury have been developed. Middle cerebral artery occlusion (MCAO) in particular reproduces both ischemic and reperfusion elements and is widely utilized as a model of ischemic stroke in rodents. However substantial variability exists in this m odel even in clonal inbred mice due to stochastic elements of the cerebral vasculature. Models such as MCAO thus exhibit significant irreducible variabilities with respect to their zone of injury as well as inducing a sizable volume of injury to the cerebrum with damage to sub-cortical structures, c...
Source: Apoptosis - May 8, 2019 Category: Molecular Biology Source Type: research
Copper-imidazo[1,2- a ]pyridines induce intrinsic apoptosis and modulate the expression of mutated p53, haem-oxygenase-1 and apoptotic inhibitory proteins in HT-29 colorectal cancer cells
In conclusion, the copper-imidazo[1,2-a]pyridines were effective inducers of apoptotic cell death at low micromolar concentrations and changed the expression levels of proteins important for cell survival and cell death. These copper complexes may be useful tools to better understand the complexity of signalling networks in cancer cell death in response to cell stress. (Source: Apoptosis)
Source: Apoptosis - May 8, 2019 Category: Molecular Biology Source Type: research
Modulation of CD95-mediated signaling by post-translational modifications: towards understanding CD95 signaling networks
AbstractCD95 is a member of the death receptor family and is well-known to promote apoptosis. However, accumulating evidence indicates that in some context CD95 has not only the potential to induce apoptosis but also can trigger non-apoptotic signal leading to cell survival, proliferation, cancer growth and metastasis. Despite extensive investigations focused on alterations in the expression level of CD95 and associated signal molecules, very few studies, however, have investigated the effects of post-translational modifications such as glycosylation, phosphorylation, palmitoylation, nitrosylation and glutathionylation on ...
Source: Apoptosis - May 7, 2019 Category: Molecular Biology Source Type: research
Role of glycogen synthase kinase following myocardial infarction and ischemia –reperfusion
Source: Apoptosis - April 26, 2019 Category: Molecular Biology Source Type: research
Cellular responses of BRCA1 -defective HCC1937 breast cancer cells induced by the antimetastasis ruthenium(II) arene compound RAPTA-T
In this study, the effects of RAPTA-T onBRCA1-defective HCC1937 breast cancer cells have been investigated, and compared to its effects onBRCA1-competent MCF-7 breast cancer cells. RAPTA-T showed a very low cytotoxicity against both tested cells. Ruthenium is found mostly in the cytoplasmic compartment of both cells. Flow cytometric analysis reveals that the compound arrests the growth of both cells by triggering the G2/M phase that led to the induction of apoptosis. At equimolar concentrations, RAPTA-T causes much more cellularBRCA1 damage in HCC1937 than in MCF-7 cells, suppressing the expression ofBRCA1 mRNA in both cel...
Source: Apoptosis - April 22, 2019 Category: Molecular Biology Source Type: research
Proteasome inhibitors trigger mutations via activation of caspases and CAD, but mutagenesis provoked by the HDAC inhibitors vorinostat and romidepsin is caspase/CAD-independent
AbstractGenotoxic anti-cancer therapies such as chemotherapy and radiotherapy can contribute to an increase in second malignancies in cancer survivors due to their oncogenic effects on non-cancerous cells. Inhibition of histone deacetylase (HDAC) proteins or the proteasome differ from chemotherapy in that they eliminate cancer cells by regulating gene expression or cellular protein equilibrium, respectively. As members of these drug classes have been approved for clinical use in recent times, we investigated whether these two drug classes exhibit similar mutagenic capabilities as chemotherapy. The HDAC inhibitors vorinosta...
Source: Apoptosis - April 16, 2019 Category: Molecular Biology Source Type: research
17-Aminogeldanamycin selectively diminishes IRE1 α-XBP1s pathway activity and cooperatively induces apoptosis with MEK1/2 and BRAF V600E inhibitors in melanoma cells of different genetic subtypes
AbstractOutcomes of melanoma patient treatment remain unsatisfactory despite accessibility of oncoprotein-targeting drugs and immunotherapy. Here, we reported that 17-aminogeldanamycin more potently activated caspase-3/7 in BRAFV600E melanoma cells than geldanamycin, another inhibitor of heat shock protein 90 (HSP90). 17-aminogeldanamycin alleviated self-triggered compensatory increase in HSP70 mRNA level and induced endoplasmic reticulum (ER) stress, which was followed by selective diminution of cytoprotective IRE1 α-XBP1s pathway activity of unfolded protein response (UPR), inhibition of ERK1/2 activity and inducti...
Source: Apoptosis - April 14, 2019 Category: Molecular Biology Source Type: research
Matrix metalloproteinase 9 induces keratinocyte apoptosis through FasL/Fas pathway in diabetic wound
This study increases understanding of elevated MMP9 which is involved in diabetic wound repair and offers some insights into novel future therapies. (Source: Apoptosis)
Source: Apoptosis - April 3, 2019 Category: Molecular Biology Source Type: research
Recombinant human lactoferrin induces apoptosis, disruption of F-actin structure and cell cycle arrest with selective cytotoxicity on human triple negative breast cancer cells
AbstractBreast cancer is the most frequently diagnosed cancer among women worldwide. Here, recombinant human lactoferrin (rhLf) expressed inPichia pastoris was tested for its potential cytotoxic activity on a panel of six human breast cancer cell lines. The rhLf cytotoxic effect was determined via a live-cell HTS imaging assay. Also, confocal microscopy and flow cytometry protocols were employed to investigate the rhLf mode of action. The rhLf revealed an effective CC50 of 91.4 and 109.46 µg/ml on non-metastatic and metastatic MDA-MB-231 cells, with favorable selective cytotoxicity index values, 11.68 and 13.99...
Source: Apoptosis - April 1, 2019 Category: Molecular Biology Source Type: research
Potential role of anastasis in cancer initiation and progression
Source: Apoptosis - March 31, 2019 Category: Molecular Biology Source Type: research
Calreticulin in phagocytosis and cancer: opposite roles in immune response outcomes
AbstractCalreticulin (CRT) is a pleiotropic and highly conserved molecule that is mainly localized in the endoplasmic reticulum. Recently, CRT has gained special interest for its functions outside the endoplasmic reticulum where it has immunomodulatory properties. CRT translocation to the cell membrane serves as an “eat me” signal and promotes efferocytosis of apoptotic cells and cancer cell removal with completely opposite outcomes. Efferocytosis results in a silenced immune response and homeostasis, while removal of dying cancer cells brought about by anthracycline treatment, ionizing-irradiation or phot odyn...
Source: Apoptosis - March 29, 2019 Category: Molecular Biology Source Type: research
Correction to: Autophagy inhibition with chloroquine reverts paclitaxel resistance and attenuates metastatic potential in human nonsmall lung adenocarcinoma A549 cells via ROS mediated modulation of β-catenin pathway
The original version of this article unfortunately contained an error in acknowledgment text. The authors would like to include a statement: “Moumita Dasgupta is supported by Junior Research Fellowship from University Grant Commission, India.” in acknowledgment section. (Source: Apoptosis)
Source: Apoptosis - March 27, 2019 Category: Molecular Biology Source Type: research
Effects of annexin A7 inhibitor-ABO on the expression and distribution of long noncoding RNA-CERNA1 in vascular endothelial cells apoptosis
In this study, we found that nuclear CERNA1 positively regulated BCL2L10, which accelerated the serum and FGF-2 starvation-induced apoptosis of VECs, by enhancing the histone modification level of H3K9ac and H3K4me3 in BCL2L10 promoter region. Furthermore, due to the paradoxical function, we investigated the variation of CERNA1 subcellular location in VECs. The results showed that, as the change of apoptosis status, CERNA1 altered the cellular distribution in VECs. And the annexin A7 inhibitor, ABO (6-amino-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine), not only increased the expression of CERNA1 by TIA-1, but also specific...
Source: Apoptosis - March 24, 2019 Category: Molecular Biology Source Type: research
Activator protein-1 and caspase 8 mediate p38 α MAPK-dependent cardiomyocyte apoptosis induced by palmitic acid
The objective of this study was to investigate mechanisms involved in palmitic acid-induced cardiomyocyte apoptosis. Human adult ventricular cardiomyocyte line (AC16 cells) exposed to high physiological levels of PA for 16 h showed enhanced transcription and phosphorylation of c-fos and c-jun subunits of AP-1 and transcription of caspase 8. When AC16 cells were transfected with small interfering RNA specific against p38α MAPK (si-p38α) for 24 or 48 h, the amplified phosphorylation of c-fos was dose-dependently attenuated, and procaspase 8 was dose-de pendently reduced. With translational knockdow...
Source: Apoptosis - March 15, 2019 Category: Molecular Biology Source Type: research
Improved in vivo targeting of BCL-2 phenotypic conversion through hollow gold nanoshell delivery
AbstractAlthough new cancer therapeutics are discovered at a rapid pace, lack of effective means of delivery and cancer chemoresistance thwart many of the promising therapeutics. We demonstrate a method that confronts both of these issues with the light-activated delivery of a Bcl-2 functional converting peptide, NuBCP-9, using hollow gold nanoshells. This approach has shown not only to increase the efficacy of the peptide 30-fold in vitro but also has shown to reduce paclitaxel resistant H460 lung xenograft tumor growth by 56.4%. (Source: Apoptosis)
Source: Apoptosis - March 15, 2019 Category: Molecular Biology Source Type: research
BDNF-mediated mitophagy alleviates high-glucose-induced brain microvascular endothelial cell injury
In this study, we investigated the role of BDNF in the hyperglycemic injury of BMECs and its associated intracellular signal transduction pathways. BMECs were treated with 33 mM glucose to imitate the endothelium under hyperglycemic conditions. The high-glucose treatment caused cell dysfunction, as evaluated by oxidative stress and cell apoptosis, which could be alleviated by BDNF. In addition, BDNF preserved mitochondrial function as assessed by mPTP opening, mitochon drial membrane potential, calcium content, and mitochondrial biogenesis markers. Western blot analysis of LC3-II, p62, and TOMM20 and the detection of...
Source: Apoptosis - March 14, 2019 Category: Molecular Biology Source Type: research
Fibroblasts from patients with idiopathic pulmonary fibrosis are resistant to cisplatin-induced cell death via enhanced CK2-dependent XRCC1 activity
AbstractIdiopathic pulmonary fibrosis (IPF) is a deadly and progressive fibrotic lung disease, but the precise etiology remains elusive. IPF is characterized by the presence of apoptosis-resistant (myo)fibroblasts that relentlessly produce a collagen-rich extracellular matrix (ECM). Recent studies showed that an anti-cancer chemotherapy drug cisplatin is implicated in the development of pulmonary fibrosis, suggesting that the treatment of cancer patients with cisplatin may alter fibroblast viability. To address this possibility, we investigated the cisplatin-induced cell death mechanism in lung fibroblasts derived from IPF...
Source: Apoptosis - March 7, 2019 Category: Molecular Biology Source Type: research
Inhibition of TNF- α-induced neuronal apoptosis by antidepressants acting through the lysophosphatidic acid receptor LPA 1
AbstractTumor necrosis factor- α (TNF-α), a pro-inflammatory cytokine considered to be implicated in the pathogenesis of major depressive disorder, is a critical regulator of neuronal cell fate. In the present study we found that TNF-α-induced apoptosis of HT22 hippocampal cells, a neuroblast-like cell line, was markedly atten uated by the antidepressants mianserin, mirtazapine and amitriptyline. The anti-apoptotic effect of the antidepressants was blocked by either pharmacological inhibition or gene silencing of the lysophosphatidic acid receptor LPA1. Mianserin failed to affect TNF- α-induced casp...
Source: Apoptosis - March 5, 2019 Category: Molecular Biology Source Type: research
Drosophila jumu modulates apoptosis via a JNK-dependent pathway and is required for other processes in wing development
AbstractPrevious studies in several model organisms have revealed that members of the Forkhead (Fkh) transcription factor family have multiple functions.Drosophila Jumeau (Jumu), a member of this family, participates in cardiogenesis, hematopoiesis and immune system homeostasis. Here, we show that loss ofjumu function positively regulates or triggers apoptosis via a JNK-dependent pathway in wing development.jumu mutants showed reduced wing size and increased apoptosis. Moreover, we observed a loss of the anterior cross vein (ACV) phenotype that was similar to that observed in wings in which JNK signaling has been ectopical...
Source: Apoptosis - February 22, 2019 Category: Molecular Biology Source Type: research
Simultaneous polychromatic flow cytometric detection of multiple forms of regulated cell death
AbstractCurrently the study of Regulated Cell Death (RCD) processes is limited to the use of lysed cell populations for Western blot analysis of each separate RCD process. We have previously shown that intracellular antigen flow cytometric analysis of RIP3, Caspase-3 and cell viability dye allowed the determination of levels of apoptosis (Caspase-3+ ve/RIP3− ve), necroptosis (RIP3Hi + ve/Caspase-3− ve) and RIP1-dependent apoptosis (Caspase-3+ ve/RIP3+ ve) in a single Jurkat cell population. The addition of more intracellular markers allows the determination o...
Source: Apoptosis - February 20, 2019 Category: Molecular Biology Source Type: research
The neuroprotective action of 3,3 ′-diindolylmethane against ischemia involves an inhibition of apoptosis and autophagy that depends on HDAC and AhR/CYP1A1 but not ERα/CYP19A1 signaling
This study demonstrated for the first time, that the neuroprotective action of 3,3′-diindolylmethane against ischemia involves an inhibition of apoptosis and autophagy and depends on AhR/CYP1A1 signaling and HDAC activity, thus creating the possi bility of developing new therapeutic strategies that target neuronal degeneration at specific molecular levels. (Source: Apoptosis)
Source: Apoptosis - February 18, 2019 Category: Molecular Biology Source Type: research
Autophagy inhibition with chloroquine reverts paclitaxel resistance and attenuates metastatic potential in human nonsmall lung adenocarcinoma A549 cells via ROS mediated modulation of β-catenin pathway
In this study we found that inhibition of autophagy with chloroquine prevented development of paclitaxel resistance in A549 cells with time and potentiated the effect of paclitaxel by increased accumulation of superoxide-producing damaged mitochondria, with elevated ROS generation, it also increased the apoptotic rate and sub G0/ G1 phase arrest with time in A549 cells treated with paclitaxel and attenuated the metastatic potential and cancer stem cell population of the paclitaxel-resistant cells by ROS mediated modulation of the Wnt/ β-catenin signaling pathway, thereby increasing paclitaxel sensitivity. ROS here pla...
Source: Apoptosis - February 14, 2019 Category: Molecular Biology Source Type: research
Minocycline promotes cardiomyocyte mitochondrial autophagy and cardiomyocyte autophagy to prevent sepsis-induced cardiac dysfunction by Akt/mTOR signaling
In conclusion, minocycline enhanced cardiomyocyte mitochondrial autophagy and cardiomyocyte autophagy and improved cardiac function. The underlying mechanisms were associated with mTORC1 inhibition and mTORC2 activation. Thus, our findings suggest that minocycline may represent a potential approach for treating myocardial injury and provide novel insights into the underlying mechanisms of myocardial injury and dysfunction after sepsis. (Source: Apoptosis)
Source: Apoptosis - February 12, 2019 Category: Molecular Biology Source Type: research
Eukaryotic elongation factor 2 (eEF2) kinase/eEF2 plays protective roles against glucose deprivation-induced cell death in H9c2 cardiomyoblasts
In conclusion, we for the first time revealed that eEF2K/eEF2 axis under GD condition mediates the inhibition of apoptotic H9c2 cell death at least in part via promotion of autophagy through AMPKα/ULK1 signaling pathway. (Source: Apoptosis)
Source: Apoptosis - February 8, 2019 Category: Molecular Biology Source Type: research
Excess active P13K rescues huntingtin-mediated neuronal cell death but has no effect on axonal transport defects
AbstractHigh levels of oxidative stress is detected in neurons affected by many neurodegenerative diseases, including huntington ’s disease. Many of these diseases also show neuronal cell death and axonal transport defects. While nuclear inclusions/accumulations likely cause cell death, we previously showed that cytoplasmic axonal accumulations can also contribute to neuronal death. However, the cellular mechanisms responsi ble for activating cell death is unclear. One possibility is that perturbations in normal axonal transport alter the function of the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)-pat...
Source: Apoptosis - February 6, 2019 Category: Molecular Biology Source Type: research
Combination treatment of podophyllotoxin and rutin promotes mouse Lgr5 + ve intestinal stem cells survival against lethal radiation injury through Wnt signaling
AbstractIt has been well established that radiation-induced gastrointestinal injury is manifested through loss of intestinal crypt stem cells and disruption of the mucosal layers, resulting in diarrhoea, weight loss, electrolyte imbalance, infection and mortality. Podophyllotoxin and rutin in combination (G-003M) has been reported to regulate endogenous cellular antioxidant defense systems and inflammatory response. However, the mechanism by which G-003M ameliorates radiation-induced intestinal stem cell (ISC) injury remains unclear. Here, we hypothesize the radioprotective potential of G-003M would amplify the intestinal ...
Source: Apoptosis - February 6, 2019 Category: Molecular Biology Source Type: research
Chemotherapeutic paclitaxel and cisplatin differentially induce pyroptosis in A549 lung cancer cells via caspase-3/GSDME activation
AbstractGasdermin E (GSDME) has an important role in inducing secondary necrosis/pyroptosis. Upon apoptotic stimulation, it can be cleaved by activated caspase-3 to generate its N-terminal fragment (GSDME-NT), which executes pyroptosis by perforating the plasma membrane. GSDME is expressed in many human lung cancers including A549 cells. Paclitaxel and cisplatin are two representative chemotherapeutic agents for lung cancers, which induce apoptosis via different action mechanisms. However, it remains unclear whether they can induce GSDME-mediated secondary necrosis/pyroptosis in lung A549 cancer cells. Here we showed that ...
Source: Apoptosis - February 1, 2019 Category: Molecular Biology Source Type: research