Endoplasmic reticulum stress and protein quality control in diabetic cardiomyopathy.
Endoplasmic reticulum (ER) stress, together with the unfolded protein response (UPR), is initially considered an adaptive response aiming at maintenance of ER homeostasis. Nonetheless, ER stress, when in excess, can eventually trigger cell apoptosis and loss of function. UPR is mediated by three major transmembrane proteins, including inositol-requiring enzyme 1 (IRE1), protein kinase RNA-like ER kinase (PERK), and activating transcription factor (ATF) 6. A unique role has been speculated for ER stress in the pathogenesis of diabetes mellitus (DM) and its complications. Recent studies have shown that ER stress is an early event associated with diabetic cardiomyopathy, and may be triggered by hyperglycemia, free fatty acids (FFAs) and inflammation. In this mini-review, we attempted to discuss the activation machinery for ER stress in response to these triggers en route to disrupted ER function and cellular autophagy or apoptosis, ultimately insulin resistance and development of diabetic cardiomyopathy. This article is part of a Special Issue entitled: Autophagy and protein quality control in cardiometabolic diseases.
Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China; Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, WY 82071, USA.
Lifang
L
Yang
Department of Cardiac Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
Dajun
D
Zhao
Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, WY 82071, USA. Electronic address: jren@uwyo.edu.
Jun
J
Ren
Department of Cardiac Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China. Electronic address: yangjian1212@hotmail.com.
Jian
J
Yang
D000818:Animals; D058065:Diabetic Cardiomyopathies / Q000378:metabolism* / Q000473:pathology*; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D008954:Models, Biological; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction; D056811:Unfolded Protein Response
D011506:Proteins
Diabetic cardiomyopathy; Endoplasmic reticulum stress; Unfolded protein response