Mdivi-1 attenuates sodium azide-induced apoptosis in H9c2 cardiac muscle cells

Abstract

The aim of the current study was to investigate the effect of mitochondrial division inhibitor 1 (Mdivi-1) in sodium azide-induced cell death in H9c2 cardiac muscle cells. Mdivi-1 is a key inhibitor of the mitochondrial division protein dynamin-related protein 1 (Drp1). Mdivi-1 was added to H9c2 cells for 3 h, after which, the cells were treated with sodium azide for 24 h. Cell viability was measured by Cell Counting kit-8 assay. DAPI staining was used to observe nuclear morphology changes by microscopy. To further investigate the role of mitochondria in sodium azide-induced cell death, mitochondrial membrane potential (ΔΨm) and the cellular ATP content were determined by JC-1 staining and ATP-dependent bioluminescence assay, respectively. Reactive oxygen species (ROS) production was also assessed by use of the specific probe 2′,7′-dichlorodihydrofluorescein diacetate. In addition, the expression of Drp1 and of the apoptosis-related proteins BCL2 apoptosis regulator (Bcl-2), and BCL2 associated X (Bax) was determined by western blotting. The present findings demonstrated that pretreatment with Mdivi-1 attenuated sodium azide-induced H9c2 cell death. Mdivi-1 pretreatment also inhibited the sodium azide-induced downregulation of Bcl-2 expression and upregulation of Bax and Drp1 expression. In addition, the mitochondrion was revealed to be the target organelle of sodium azide-induced toxicity in H9c2 cells. Mdivi-1 pretreatment moderated the dissipation of ΔΨm, preserved the cellular ATP contents and suppressed the production of ROS. The results suggested that the mechanism of sodium azide-induced cell death in H9c2 cells may involve the mitochondria-dependent apoptotic pathway. The present results indicated that Mdivi-1 may have a cardioprotective effect against sodium azide-induced apoptosis in H9c2 cardiac muscle cells.

PTEN inhibition attenuates endothelial cell apoptosis in coronary heart disease via modulating the AMPK–CREB–Mfn2‐mitophagy signaling pathway

“…Excessive mitochondrial fission causes the uneven distribution of mitochondrial DNA into daughter mitochondria, leading to the inability of mitochondria to produce sufficient ATP (Gorick, Sheybani, Curley, & Price, ; Ju et al, ). In our study, we found that ox‐LDL‐induced oxidative stress altered the mitochondrial membrane, reducing mitochondrial potential and opening the mPTP (Gao et al, ; X. Xu et al, ). This mitochondrial functional and structural damage was accompanied by mitochondrial apoptosis in endothelial cells.…”

Comparative Biochemical Profiling of Aluminum Chloride and Sodium Azide Induced Neuroinflammation and Cardiometabolic Disturbance

“…The current work also revealed that AlCl 3 (50 mg/kg/day) significantly elevated the serum levels of cholesterol, TGs, and LDL with a reduced serum level of HDL (Figure ), while at a high dose, NaN 3 (17 mg/kg/day) caused mortality. Investigations have shown that NaN 3 can cause sudden lowering of blood pressure, tachycardia, cardiac arrhythmia, and cardiac toxicity; moreover, late onset of hypotension presents an ominous sign of death . Any of these effects reported earlier could be a cause of sudden death in the experimental animals of the current study exposed to NaN 3 (17 mg/kg/day).…”

“…Investigation has found that aluminum toxicities may include fibrosis, myocarditis, thrombosis, ischemic stroke, AD, dementia, pancreatitis, pancreatic necrosis, and DM . Numerous reports have revealed that NaN 3 poisoning causes severe hypoxemia, myocardial fibrosis, and extensive damage in the nervous and cardiac systems . In this study, fibrosis of the brain, heart, and pancreatic tissue, after exposure to different doses of AlCl 3 and NaN 3 , was analyzed via Masson’s trichrome staining (Figures , , ).…”

“…Investigations have shown that NaN 3 can cause sudden lowering of blood pressure, tachycardia, cardiac arrhythmia, and cardiac toxicity; moreover, late onset of hypotension presents an ominous sign of death. 22 Any of these effects reported earlier could be a cause of sudden death in the experimental animals of the current study exposed to NaN 3 (17 mg/kg/day).…”

Downregulation of SIRT3 Aggravates Lung Ischemia Reperfusion Injury by Increasing Mitochondrial Fission and Oxidative Stress through HIF-1α-Dependent Mechanisms

“…However, in some pathological conditions, such as acute kidney injury and diabetic nephropathy [ 11 , 12 ], excessive mitochondrial fission results in increased mitochondrial fragmentation which inhibits the cellular respiratory chain, leading to cellular dysfunction and aggravating tissue damage [ 13 , 14 ]. Mitochondrial fission is primarily mediated by dynamin-related protein 1 (Drp-1) [ 15 ], a member of the dynamin family of large GTPases, mostly localized in the cytoplasm [ 16 ]. Drp-1 is recruited to the outer membrane of mitochondria by a variety of adaptor proteins and then aggregates along the site of mitochondrial fission in the future [ 17 , 18 ].…”