title: Popdc1/Bves Functions in the Preservation of Cardiomyocyte Viability While Affecting Rac1 Activity and Bnip3 Expression.
abstract: The Popeye domain containing1, also called Bves (Popdc1/Bves), is a transmembrane protein that functions in muscle regeneration, heart rate regulation, hypoxia tolerance, and ischemia preconditioning. The expression of Popdc1/Bves is elevated in cardiomyocytes maintained in serum free defined medium. We hypothesized that Popdc1/Bves is important for cardiomyocyte survival under the stress of serum deprivation and investigated the mechanisms involved. A deficit in Popdc1/Bves, achieved by siRNA-mediated gene silencing, results in cardiomyocyte injury and death, upregulation of the pro-apoptotic protein Bcl-2/adenovirus E1B 19-kDa interacting protein3 (Bnip3), as well as reduction in Rac1-GTPase activity and in Akt phosphorylation. Combined Popdc1/Bves and Bnip3 silencing attenuated cell injury and prevented Bnip3 upregulation induced by the silencing of Popdc1/Bves alone. Chromatin immunoprecipitation indicated an increased binding of the transcription factor FoxO3 to the Bnip3 promoter although augmentation of FoxO3 in the nuclei was not detected. By contrast, the transcription factor NFκB was excluded from the nuclei of Popdc1/Bves deficient cardiomyocytes and exhibited decreased binding to the Bnip3 promoter. The data indicates that Popdc1/Bves plays a role in the preservation of cardiomyocyte viability under serum deficiency through the alteration of Rac1 activity and the regulation of Bnip3 expression by FoxO3 and NFκB transcription factors pointing to Popdc1/Bves as a potential target to enhance heart protection. J. Cell. Biochem. 118: 1505-1517, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: The Felsenstein Medical Research Center, Sackler Faculty of Medicine and Rabin Medical Center, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Kliminski
authors.affiliation: The Felsenstein Medical Research Center, Sackler Faculty of Medicine and Rabin Medical Center, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Uziel
authors.affiliation: The Felsenstein Medical Research Center, Sackler Faculty of Medicine and Rabin Medical Center, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Gania
authors.initials: G
authors.lastname: Kessler-Icekson
mesh_terms: D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D000071316:Forkhead Box Protein O3 / Q000378:metabolism; D005786:Gene Expression Regulation; D020868:Gene Silencing; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D017208:Rats, Wistar; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C505650:BNIP3 protein, rat; C524261:Bves protein, rat; D016895:Culture Media, Serum-Free; C499515:FOXO3 protein, rat; D000071316:Forkhead Box Protein O3; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D016328:NF-kappa B; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein
keywords: Bnip3; CARDIOMYOCYTES; CELL VIABILITY; Popdc1/Bves; Rac1