RGD Reference Report - Exogenous H2S regulates endoplasmic reticulum-mitochondria cross-talk to inhibit apoptotic pathways in STZ-induced type I diabetes. - Rat Genome Database

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Exogenous H2S regulates endoplasmic reticulum-mitochondria cross-talk to inhibit apoptotic pathways in STZ-induced type I diabetes.

Authors: Yang, Fan  Yu, Xiangjing  Li, Ting  Wu, Jianjun  Zhao, Yajun  Liu, Jiaqi  Sun, Aili  Dong, Shiyun  Wu, Jichao  Zhong, Xin  Xu, Changqing  Lu, Fanghao  Zhang, Weihua 
Citation: Yang F, etal., Am J Physiol Endocrinol Metab. 2017 Mar 1;312(3):E190-E203. doi: 10.1152/ajpendo.00196.2016. Epub 2016 Dec 20.
RGD ID: 12910739
Pubmed: PMID:27998959   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpendo.00196.2016   (Journal Full-text)

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 cytochrome c (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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Diabetes Mellitus  ISOMfn2 (Rattus norvegicus)12910739; 12910739protein:increased expression:heart and mitochondrion (rat)RGD 
Experimental Diabetes Mellitus  IEP 12910739protein:increased expression:heart and mitochondrion (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mfn2  (mitofusin 2)

Genes (Mus musculus)
Mfn2  (mitofusin 2)

Genes (Homo sapiens)
MFN2  (mitofusin 2)


Additional Information