title: Exogenous H2S regulates endoplasmic reticulum-mitochondria cross-talk to inhibit apoptotic pathways in STZ-induced type I diabetes.
abstract: The upregulation of reactive oxygen species (ROS) is a primary cause of cardiomyocyte apoptosis in diabetes cardiomyopathy (DCM). Mitofusin-2 (Mfn-2) is a key protein that bridges the mitochondria and endoplasmic reticulum (ER). Hydrogen sulfide (H2S)-mediated cardioprotection is related to antioxidant effects. The present study demonstrated that H2S inhibited the interaction between the ER and mitochondrial apoptotic pathway. This study investigated cardiac function, ultrastructural changes in the ER and mitochondria, apoptotic rate using TUNEL, and the expression of ER stress-associated proteins and mitochondrial apoptotic proteins in cardiac tissues in STZ-induced type I diabetic rats treated with or without NaHS (donor of H2S). Mitochondria of cardiac tissues were isolated, and MPTP opening and cytochromec(cyt C) and Mfn-2 expression were also detected. Our data showed that hyperglycemia decreased the cardiac function by ultrasound cardiogram, and the administration of exogenous H2S ameliorated these changes. We demonstrated that the expression of ER stress sensors and apoptotic rates were elevated in cardiac tissue of DCM and cultured H9C2 cells, but the expression of these proteins was reduced following exogenous H2S treatment. The expression of mitochondrial apoptotic proteins, cyt C, and mPTP opening was decreased following treatment with exogenous H2S. In our experiment, the expression and immunofluorescence of Mfn-2 were both decreased after transfection with Mfn-2-siRNA. Hyperglycemia stimulated ER interactions and mitochondrial apoptotic pathways, which were inhibited by exogenous H2S treatment through the regulation of Mfn-2 expression.
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, China; and.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, China; and.
authors.forename: Xiangjing
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, China; and.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Cardiology, the Fourth Hospital of Harbin Medical University, Harbin, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, China; and.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, China; and.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, China; and.
authors.forename: Aili
authors.initials: A
authors.lastname: Sun
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, China; and.
authors.forename: Shiyun
authors.initials: S
authors.lastname: Dong
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, China; and.
authors.forename: Jichao
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, China; and.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, China; and.
authors.forename: Changqing
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, China; and.
authors.forename: Fanghao
authors.initials: F
authors.lastname: Lu
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, China; and zhangwh116@126.com.
authors.forename: Weihua
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D045304:Cytochromes c / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D058065:Diabetic Cardiomyopathies; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000648:ultrastructure; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D020558:GTP Phosphohydrolases; D064426:Gasotransmitters / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D008854:Microscopy, Electron; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D064426:Gasotransmitters; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D013440:Sulfides; D045304:Cytochromes c; D020558:GTP Phosphohydrolases; C489710:Mfn2 protein, rat; C025451:sodium bisulfide; D006862:Hydrogen Sulfide
keywords: Mitofusin-2; apoptosis; diabetic cardiomyopathy; endoplasmic reticulum stress; oxidative stress