Bcl‐2‐associated athanogene 5 overexpression attenuates catecholamine‐induced vascular endothelial cell apoptosis
- 24 June 2020
- journal article
- research article
- Published by Wiley in Journal of Cellular Physiology
- Vol. 236 (2), 946-957
- https://doi.org/10.1002/jcp.29904
Abstract
Bcl‐2 associated athanogene 5 (Bag5) is a novel endoplasmic reticulum (ER) regulator. However, its role in catecholamine‐induced endothelial cells damage has not been fully understood. In our study, catecholamine was used to mimic hypertension‐related endothelial cell damage. Then, western blots, enzyme‐linked immunosorbent assay, immunofluorescence, quantitative polymerase chain reaction and pathway analysis were conducted to analyze the role of Bag5 in endothelial cell damage in response to catecholamine. Our results indicated that the endothelial cell viability was impaired by catecholamine. Interestingly, Bag5 overexpression significantly reversed endothelial cell viability. Mechanistically, Bag5 overexpression inhibited ER stress, attenuated oxidative stress and repressed inflammation in catecholamine‐treated endothelial cells. These beneficial effects finally contributed to endothelial cell survival under catecholamine treatment. Pathway analysis demonstrated that Bag5 was under the control of the mitogen‐activated protein kinase (MAPK)–extracellular‐signal‐regulated kinase (ERK) signaling pathway. Reactivation of the MAPK–ERK pathway could upregulate Bag5 expression and thus promote endothelial cell survival through inhibiting oxidative stress, ER stress, and inflammation. Altogether, our results illustrate that Bag5 overexpression sustains endothelial cell survival in response to catecholamine treatment. This finding identifies Bag5 downregulation and the inactivated MAPK–ERK pathway as potential mechanisms underlying catecholamine‐induced endothelial cell damage.This publication has 87 references indexed in Scilit:
- Cardiac-specific inactivation of LPP3 in mice leads to myocardial dysfunction and heart failureRedox Biology, 2018
- Metformin selectively targets redox control of complex I energy transductionRedox Biology, 2018
- Pre-culture in endothelial growth medium enhances the angiogenic properties of adipose-derived stem/stromal cellsAngiogenesis, 2018
- N-tert-butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe (BOC2) inhibits the angiogenic activity of heparin-binding growth factorsAngiogenesis, 2017
- GRP78 at the Centre of the Stage in Cancer and NeuroprotectionFrontiers in Neuroscience, 2017
- Ginkgolide K protects the heart against endoplasmic reticulum stress injury by activating the inositol‐requiring enzyme 1α/X box‐binding protein‐1 pathwayBritish Journal of Pharmacology, 2016
- Cortistatin Improves Cardiac Function After Acute Myocardial Infarction in Rats by Suppressing Myocardial Apoptosis and Endoplasmic Reticulum StressJournal of Cardiovascular Pharmacology and Therapeutics, 2016
- Inhibition of Soluble Epoxide Hydrolase Limits Mitochondrial Damage and Preserves Function Following Ischemic InjuryFrontiers in Pharmacology, 2016
- Spermine inhibits Endoplasmic Reticulum Stress - induced Apoptosis: a New Strategy to Prevent Cardiomyocyte ApoptosisCellular Physiology and Biochemistry, 2016
- The mitochondria as a target for cardioprotection in acute myocardial ischemiaPharmacology & Therapeutics, 2014