title: GRP78 Interacting Partner Bag5 Responds to ER Stress and Protects Cardiomyocytes From ER Stress-Induced Apoptosis.
abstract: Bag5 is a member of the BAG family of molecular chaperone regulators and is unusual in that it consists of five BAG domains, which function as modulators of chaperone activity. Bag family proteins play a key role in cellular as well as in cardiac function and their differential expression is reported in heart failure. In this study, we examined the importance of a Bag family member protein, Bag5, in cardiomyocytes during endoplasmic reticulum (ER) stress. We found that expression of Bag5 in cardiomyocytes is significantly increased with the induction of ER stress in a time dependent manner. We have taken gain-in and loss-of functional approaches to characterize Bag5 protein function in cardiomyocytes. Adenoviral mediated expression of Bag5 significantly decreased cell death as well as improved cellular viability in ER stress. Along with this, ER stress-induced CHOP protein expression is significantly decreased in cells that overexpress Bag5. Conversely, we found that siRNA-mediated knockdown of Bag5 caused cell death, increased cytotoxicity, and decreased cellular viability in cardiomyocytes. Mechanistically, we found that Bag5 protein expression is significantly increased in the ER during ER stress and that this in turn modulates GRP78 protein stability and reduces ER stress. This study suggests that Bag5 is an important regulator of ER function and so could be exploited as a tool to improve cardiomyocyte function under stress conditions. J. Cell. Biochem. 117: 1813-1821, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Neuroscience, Comprehensive NeuroAIDS Center, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.
authors.forename: Manish K
authors.initials: MK
authors.lastname: Gupta
authors.affiliation: Department of Neuroscience, Comprehensive NeuroAIDS Center, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.
authors.forename: Farzaneh G
authors.initials: FG
authors.lastname: Tahrir
authors.affiliation: Department of Neuroscience, Comprehensive NeuroAIDS Center, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.|Department of Biology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania.
authors.forename: Tijana
authors.initials: T
authors.lastname: Knezevic
authors.affiliation: Department of Neuroscience, Comprehensive NeuroAIDS Center, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.
authors.forename: Martyn K
authors.initials: MK
authors.lastname: White
authors.affiliation: Department of Neuroscience, Comprehensive NeuroAIDS Center, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gordon
authors.affiliation: Center for Translational Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.|Department of Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.
authors.forename: Joseph Y
authors.initials: JY
authors.lastname: Cheung
authors.affiliation: Department of Neuroscience, Comprehensive NeuroAIDS Center, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.
authors.forename: Kamel
authors.initials: K
authors.lastname: Khalili
authors.affiliation: Department of Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.|Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Feldman
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D059865:Endoplasmic Reticulum Stress; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D055550:Protein Stability; D051381:Rats; D017207:Rats, Sprague-Dawley; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D006360:Heat-Shock Proteins; C496514:Bag5 protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP
keywords: APOPTOSIS; BAG5; CARDIOMYOCYTES; ER STRESS