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Complement C5b-9 and Cancer: Mechanisms of Cell Damage, Cancer Counteractions, and Approaches for Intervention
In conclusion, osmotic burst of inflated complement-damaged cells may occur, but these bursts are most likely a consequence of metabolic collapse of the cell rather than the cause of cell death. The Complement Cell Death Mediator: A Concerted Action of Toxic Moieties Membrane pores caused by complement were first visualized by electron microscopy on red blood cell membranes as large ring structures (22). Similar lesions were viewed on E. coli cell walls (23). Over the years, ample information on the fine ultrastructure of the MAC that can activate cell death has been gathered (24) and has been recently further examined (...
Source: Frontiers in Immunology - April 9, 2019 Category: Allergy & Immunology Source Type: research

Mitochondrial respiratory chain deficiency inhibits lysosomal hydrolysis.
Abstract Mitochondria are key organelles for cellular metabolism, and regulate several processes including cell death and macroautophagy/autophagy. Here, we show that mitochondrial respiratory chain (RC) deficiency deactivates AMP-activated protein kinase (AMPK, a key regulator of energy homeostasis) signaling in tissue and in cultured cells. The deactivation of AMPK in RC-deficiency is due to increased expression of the AMPK-inhibiting protein FLCN (folliculin). AMPK is found to be necessary for basal lysosomal function, and AMPK deactivation in RC-deficiency inhibits lysosomal function by decreasing the activity...
Source: Autophagy - March 26, 2019 Category: Cytology Authors: Fernandez-Mosquera L, Yambire KF, Couto R, Pereyra L, Pabis K, Ponsford AH, Diogo CV, Stagi M, Milosevic I, Raimundo N Tags: Autophagy Source Type: research

Ubiquitination of UVRAG by SMURF1 promotes autophagosome maturation and inhibits hepatocellular carcinoma growth.
Abstract UVRAG (UV radiation resistance associated) is an important regulator of mammalian macroautophagy/autophagy by interacting with BECN1, PIK3C3, and RUBCN. Phosphorylation of UVRAG by MTORC1 negatively regulates autophagosome maturation under nutrient-enriched conditions. However, how UVRAG ubiquitination is regulated is still unknown. Here we report that UVRAG is ubiquitinated by SMURF1 at lysine residues 517 and 559, which decreases the association of UVRAG with RUBCN and promotes autophagosome maturation. However, the deubiquitinase ZRANB1 specifically cleaves SMURF1-induced K29 and K33-linked polyubiquit...
Source: Autophagy - January 27, 2019 Category: Cytology Authors: Feng X, Jia Y, Zhang Y, Ma F, Zhu Y, Hong X, Zhou Q, He R, Zhang H, Jin J, Piao D, Huang H, Li Q, Qiu X, Zhang Z Tags: Autophagy Source Type: research

Delivery of nucleic acids to ex vivo porcine airways using electrospray.
CONCLUSIONS: We report ex vivo delivery of nucleic acids to porcine lung tissue via electrospray and bronchoscopic electrospray delivery of nucleic acid to an ex vivo porcine lung model. PMID: 30675820 [PubMed - as supplied by publisher]
Source: Experimental Lung Research - January 25, 2019 Category: Respiratory Medicine Tags: Exp Lung Res Source Type: research

Identification of NFAT5 as a transcriptional regulator of the EDN1gene in collecting duct.
Abstract The inner medullary collecting duct (IMCD) produces very high levels of endothelin-1 (ET-1) that acts as an autocrine inhibitor of IMCD Na+and water reabsorption. Recent studies suggest that IMCD ET-1 production is enhanced by extracellular hypertonicity as can occur during high salt intake. While NFAT5 has been implicated in the IMCD ET-1 hypertonicity response, no studies in any cell type have identified NFAT5 as a transcriptional regulator of the EDN1gene; the currently study examined this using a mouse IMCD cell line (IMCD3). Media hypertonicity increased IMCD3 ET-1 mRNA in a dose- and time-dependent ...
Source: Am J Physiol Renal P... - January 9, 2019 Category: Urology & Nephrology Authors: Lakshmipathi J, Wheatley W, Kumar A, Mercenne G, Rodan AR, Kohan DE Tags: Am J Physiol Renal Physiol Source Type: research

Activator protein-1 contributes to the NaCl-induced expression of VEGF and PlGF in RPE cells.
Conclusions: The data indicate that AP-1 is activated in RPE cells in response to extracellular hyperosmolarity and mediates in part via the NaCl-induced expression of VEGF and PlGF, and secretion of PlGF. It is suggested that high consumption of dietary salt may exacerbate the angiogenic response of RPE cells in part via activation of AP-1. PMID: 30310263 [PubMed - in process]
Source: Molecular Vision - October 13, 2018 Category: Molecular Biology Tags: Mol Vis Source Type: research

Osmotic and hypoxic induction of the complement factor C9 in cultured human retinal pigment epithelial cells: Regulation of VEGF and NLRP3 expression.
Conclusions: The expression of the C9 gene in cultured RPE cells is highly induced by extracellular hyperosmolarity, hypoxia, and oxidative stress. The data may support the assumption that C9 gene expression may stimulate the expression of inflammatory (NLRP3) and angiogenic growth factors (VEGF) in RPE cells. Extracellular C9 protein may attenuate this effect, in part via negative regulation of the C9 mRNA level. PMID: 30090015 [PubMed - in process]
Source: Molecular Vision - August 11, 2018 Category: Molecular Biology Tags: Mol Vis Source Type: research

β-arrestin 2 attenuates lipopolysaccharide-induced liver injury via inhibition of TLR4/NF-κB signaling pathway-mediated inflammation in mice.
CONCLUSION: β-arrestin 2 can protect liver tissue from LPS-induced injury via inhibition of TLR4/NF-κB signaling pathway-mediated inflammation. PMID: 29375207 [PubMed - in process]
Source: World Journal of Gastroenterology : WJG - January 14, 2018 Category: Gastroenterology Authors: Jiang MP, Xu C, Guo YW, Luo QJ, Li L, Liu HL, Jiang J, Chen HX, Wei XQ Tags: World J Gastroenterol Source Type: research

Interfering RNA against PKC- α Inhibits TNF-α-induced IP3R1 Expression and Improves Glomerular Filtration Rate in Rats with Fulminant Hepatic Failure.
CONCLUSION: RNAi targeting PKC-α inhibited TNF-α-induced IP3R1 overexpression, and in turn improved compromised GFR in the development of acute kidney injury during FHF in rats. PMID: 29357415 [PubMed - as supplied by publisher]
Source: American Journal of Physiology. Renal Physiology - January 10, 2018 Category: Physiology Authors: Wang DL, Dai WY, Wang W, Wen Y, Zhou Y, Zhao YT, Wu J, Liu P Tags: Am J Physiol Renal Physiol Source Type: research

Activation of insulin-like growth factor 1 receptor participates downstream of GPR30 in estradiol-17 β-D-glucuronide-induced cholestasis in rats.
In conclusion, the activation of IGF-1R is a key factor in the alteration of canalicular transporter function and localization induced by E17G, and its activation follows that of GPR30 and precedes that of PI3K/Akt. PMID: 29090346 [PubMed - as supplied by publisher]
Source: Archives of Toxicology - October 31, 2017 Category: Toxicology Authors: Barosso IR, Miszczuk GS, Ciriaci N, Andermatten RB, Maidagan PM, Razori V, Taborda DR, Roma MG, Crocenzi FA, Sánchez Pozzi EJ Tags: Arch Toxicol Source Type: research

NF- κB-Dependent Upregulation of (Pro)Renin Receptor Mediates High NaCl-Induced Apoptosis in Mouse Inner Medullary Collecting Duct Cells.
In conclusion, PRR expression is induced by high NaCl through NF-κB and contributes to cell apoptosis under this circumstance. PMID: 29021196 [PubMed - as supplied by publisher]
Source: Am J Physiol Cell Ph... - October 11, 2017 Category: Cytology Authors: Su J, Liu X, Xu C, Lu X, Wang F, Fang H, Lu A, Qiu Q, Li C, Yang T Tags: Am J Physiol Cell Physiol Source Type: research

Regulation of Chromatin Assembly and Cell Transformation by Formaldehyde Exposure in Human Cells
Conclusions: We propose that the inhibition of chromatin assembly represents a novel mechanism of cell transformation induced by the environmental and occupational chemical carcinogen FA. https://doi.org/10.1289/EHP1275 Received: 25 October 2016 Revised: 19 May 2017 Accepted: 23 May 2017 Published: 21 September 2017 Address correspondence to C. Jin, Dept. of Environmental Medicine, New York University School of Medicine, 57 Old Forge Rd., Tuxedo Park, NY 10987 USA. Telephone: (845) 731-3602. Email: Chunyuan.jin@nyumc.org *Current affiliation: Medical School of Nanjing University, Nanjing, China. †Current affiliatio...
Source: EHP Research - September 21, 2017 Category: Environmental Health Authors: Daniil Lyalko Tags: Research Source Type: research

Abstract P120: Down Regulation of Add3 in Astrocytes Induces Pro-inflammatory and Fibrotic Factors and May Contribute to Alzheimer’S-related Dementias Session Title: Onsite Poster Competition I With Reception
We genetically mapped a mutation in Add3 in FHH rats that decreases Add3 expression in various tissues, including brain and cerebral vessels, and further decreases with age in comparison with FHH.1BN congenic rats in which Chr. 1 from BN rats containing 15 genes, including Add3, was transferred onto FHH genetic background. More recently, we demonstrated that Add3 dysfunction contributes to cerebral vascular impairments in FHH rats, and they exhibit BBB leakage and neurodegeneration after the development of hypertension. In addition, Aβ protein expression in the brain in FHH rats is increased as early as 8 weeks of age. Re...
Source: Hypertension - September 14, 2017 Category: Cardiology Authors: Paige N Mims, Sheshank Shekhar, Shaoxun Wang, Olivia Travis, Fan Fan Tags: Poster Abstract Presentations Source Type: research

Elevation of fumarase attenuates hypertension and can result from a nonsynonymous sequence variation or increased expression depending on rat strain
The activity of fumarase, an enzyme in the tricarboxylic acid cycle, is lower in Dahl salt-sensitive SS rats compared with SS.13BN rats. SS.13BN rats have a Brown Norway (BN) allele of fumarase and exhibit attenuated hypertension. The SS allele of fumarase differs from the BN allele by a K481E sequence variation. It remains unknown whether higher fumarase activities can attenuate hypertension and whether the mechanism is relevant without the K481E variation. We developed SS-TgFh1 transgenic rats overexpressing fumarase on the background of the SS rat. Hypertension was attenuated in SS-TgFh1 rats. Mean arterial pressure in ...
Source: Physiological Genomics - September 8, 2017 Category: Genetics & Stem Cells Authors: Usa, K., Liu, Y., Geurts, A. M., Cheng, Y., Lazar, J., Baker, M. A., Grzybowski, M., He, Y., Tian, Z., Liang, M. Tags: Research Articles Source Type: research

Role for reactive oxygen species in flow-stimulated inner medullary collecting duct endothelin-1 production
Inner medullary collecting duct (IMCD)-derived endothelin-1 (ET-1) is stimulated by volume expansion, in part through augmented luminal flow, whereupon it can elicit natriuresis and diuresis. Since flow can alter nitric oxide (NO) and reactive oxygen species (ROS), both of which can affect collecting duct salt transport, we asked whether NO and/or ROS mediate flow-stimulated IMCD ET-1. Mouse IMCD3 cells were exposed to flow, and ET-1/GAPDH mRNA was assessed. A shear stress of 10 dyn/cm2 for 1 h increased ET-1 mRNA by fourfold compared with no flow (ET-1 flow response). Global NO synthase (NOS) inhibition [NG-nitro-l-argini...
Source: AJP: Renal Physiology - August 10, 2017 Category: Urology & Nephrology Authors: Wheatley, W., Kohan, D. E. Tags: RESEARCH ARTICLE Source Type: research

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