Diallyl trisulfide ameliorates myocardial ischemia–reperfusion injury by reducing oxidative stress and endoplasmic reticulum stress-mediated apoptosis in type 1 diabetic rats: role of SIRT1 activation

Abstract

Diallyl trisulfide (DATS) protects against apoptosis during myocardial ischemia-reperfusion (MI/R) injury in diabetic state, although the underlying mechanisms remain poorly defined. Previously, we and others demonstrated that silent information regulator 1 (SIRT1) activation inhibited oxidative stress and endoplasmic reticulum (ER) stress during MI/R injury. We hypothesize that DATS reduces diabetic MI/R injury by activating SIRT1 signaling. Streptozotocin (STZ)-induced type 1 diabetic rats were subjected to MI/R surgery with or without perioperative administration of DATS (40 mg/kg). We found that DATS treatment markedly improved left ventricular systolic pressure and the first derivative of left ventricular pressure, reduced myocardial infarct size as well as serum creatine kinase and lactate dehydrogenase activities. Furthermore, the myocardial apoptosis was also suppressed by DATS as evidenced by reduced apoptotic index and cleaved caspase-3 expression. However, these effects were abolished by EX527 (the inhibitor of SIRT1 signaling, 5 mg/kg). We further found that DATS effectively upregulated SIRT1 expression and its nuclear distribution. Additionally, PERK/eIF2α/ATF4/CHOP-mediated ER stress-induced apoptosis was suppressed by DATS treatment. Moreover, DATS significantly activated Nrf-2/HO-1 antioxidant signaling pathway, thus reducing Nox-2/4 expressions. However, the ameliorative effects of DATS on oxidative stress and ER stress-mediated myocardial apoptosis were inhibited by EX527 administration. Taken together, these data suggest that perioperative DATS treatment effectively ameliorates MI/R injury in type 1 diabetic setting by enhancing cardiac SIRT1 signaling. SIRT1 activation not only upregulated Nrf-2/HO-1-mediated antioxidant signaling pathway but also suppressed PERK/eIF2α/ATF4/CHOP-mediated ER stress level, thus reducing myocardial apoptosis and eventually preserving cardiac function.

Diallyl Trisulfide (DATS) Suppresses AGE-Induced Cardiomyocyte Apoptosis by Targeting ROS-Mediated PKCδ Activation

“…In endothelial cells, dynamin-related protein 1 (Drp1) triggered mitochondria dysfunction, which was reversed under DATS administration [30]. Silent information regulator l (SIRT1), which acts as the regulator of mitochondrial biogenesis, was significantly enhanced by DATS in myocardial ischemia-reperfusion (MI/R) injury models [31]. Therefore, reviving mitochondrial damage may be another way that DATS can protect cardiac cells from apoptosis.…”

Cell death rocks

“…A number of recently published papers should be highlighted. It was found that the mechanism by which diallyl trisulfide protects against apoptosis during myocardial ischemia-reperfusion injury in diabetic disease, involves activation of silent information regulator-1 (SIRT1) [11]. Another paper related to cardiovascular disease reports on the role of stromal cell-derived factor-1 (SDF-1) in stimulating TNF-mediated apoptosis in cardiac myocytes.…”

Deciphering the roles of FOXO1 in human neoplasms

“…Apoptosis is also referred to as programmed cell death . Resisting apoptosis is one of the most prominent characteristics of neoplasms.…”

“…Apoptosis is also referred to as programmed cell death. [39][40][41][42][43][44][45][46] Resisting apoptosis is one of the most prominent characteristics of neoplasms. MHY-449, a novel cytotoxic drug, can induce apoptotic cell death in human PC3 prostate cancer cells by downregulating the phosphorylation levels of FOXO1, which is evident in the increased activity of caspase-3, caspase-8 and caspase.…”