title: Bis(maltolato)oxovanadium(IV) (BMOV) Attenuates Apoptosis in High Glucose-Treated Cardiac Cells and Diabetic Rat Hearts by Regulating the Unfolded Protein Responses (UPRs).
abstract: Endoplasmic reticulum stress (ERS)-induced unfolded protein response (UPR) and the subsequent cell deaths are essential steps in the pathogenesis of diabetic cardiomyopathy (DCM), a main cause of diabetics' morbidity and mortalities. The bis(maltolato)oxovanadium(IV) (BMOV), a potent oral vanadium complex with anti-diabetic properties and insulin-mimicking effects, was shown to improve cardiac dysfunctions in diabetic models. Here, we examined the effects of BMOV on UPR pathway protein expression and apoptotic cell deaths in both high glucose-treated cardiac H9C2 cells and in the hearts of diabetic rats. We show that in both the high glucose-treated cardiac cells and in the hearts of streptozotocin (STZ) diabetic rats, there was an overall activation of the UPR signaling, including both apoptotic (e.g., the cascades of PERK/EIf2α/ATF4/CHOP and of IRE1/caspase 12/caspase 3) and pro-survival (GRP78 and XBP1) signaling. A high amount of apoptotic cell deaths was also detected in both diabetic conditions. The administration of BMOV suppressed both the apoptotic and pro-survival UPR signaling and significantly attenuated apoptotic cell deaths in both conditions. The overall suppression of UPR signaling by BMOV suggests that the drug protects diabetic cardiomyopathy by counteracting reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress. Our findings lend support to promote the use of BMOV in the treatment of diabetic heart diseases.
authors.affiliation: Department of Cardiology, Bethune First Hospital of Jilin University, 71 Xinmin St., Chaoyang District, ChangChun, 130021, China. congxiaoqiang@hotmail.com.
authors.forename: Xiao-Qiang
authors.initials: XQ
authors.lastname: Cong
authors.affiliation: Department of Anesthesiology, Bethune First Hospital of Jilin University, 71 Xinmin St., Chaoyang District, Changchun, Jilin, 130021, China.
authors.forename: Mei-Hua
authors.initials: MH
authors.lastname: Piao
authors.affiliation: The People's Hospital of Jilin Province, Changchun, 130021, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Public Health, Jilin University, Changchun, 130021, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xie
authors.affiliation: School of Public Health, Jilin University, Changchun, 130021, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D058065:Diabetic Cardiomyopathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005947:Glucose / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011753:Pyrones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D056811:Unfolded Protein Response / Q000187:drug effects*; D014638:Vanadates / Q000494:pharmacology*
chemical_list: D011753:Pyrones; C074212:bis(maltolato)oxovanadium(IV); D014638:Vanadates; D005947:Glucose
keywords: Apoptosis; Bis(maltolato)oxovanadium(IV) (BMOV); Diabetic cardiomyopathy; Diabetic rats; H9C2 cells; Unfolded protein response