The role of ZFP580, a novel zinc finger protein, in TGF-mediated cytoprotection against chemical hypoxia-induced apoptosis in H9c2 cardiac myocytes

Abstract

Zing finger protein 580 (ZFP580) is a novel Cys2-His2 zinc-finger transcription factor that has an anti-apoptotic role in myocardial cells. It is involved in the endothelial transforming growth factor-β1 (TGF-β1) signal transduction pathway as a mothers against decapentaplegic homolog (Smad)2 binding partner. The aim of the present study was to determine the involvement of ZFP580 in TGF-β1-mediated cytoprotection against chemical hypoxia-induced apoptosis, using H9c2 cardiac myocytes. Hypoxia was chemically induced in H9c2 myocardial cells by exposure to cobalt chloride (CoCl2). In response to hypoxia, cell viability was decreased, whereas the expression levels of hypoxia inducible factor-1α and ZFP580 were increased. Pretreatment with TGF-β1 attenuated CoCl2-induced cell apoptosis and upregulated ZFP580 protein expression; however, these effects could be suppressed by SB431542, an inhibitor of TGF-β type I receptor and Smad2/3 phosphorylation. Furthermore, suppression of ZFP580 expression by RNA interference reduced the anti-apoptotic effects of TGF-β1 and thus increased CoCl2-induced apoptosis. B-cell lymphoma (Bcl)-2-associated X protein/Bcl-2 ratio, reactive oxygen species generation and caspase-3 activation were also increased following ZFP580 inactivation. In conclusion, these results indicate that ZFP580 is a component of the TGF-β1/Smad signaling pathway, and is involved in the protective effects of TGF-β1 against chemical hypoxia-induced cell apoptosis, through inhibition of the mitochondrial apoptotic pathway.

Telmisartan cardioprotects from the ischaemic/hypoxic damage through a miR‐1‐dependent pathway

“…[23][24][25]54,55 These lead to the hydroxylase enzyme inactivation, hypoxia-inducible factor HIF-1α stabilization, ROS generation, apoptosis and increased Bax/Bcl-2 ratio followed by activation of caspase-3 cleavage. 55,56 The data obtained in the present study on H9c2 cells confirmed the reduction in Cnx43, KCNQ1 and Bcl-2 expression following exposure to the hypoxia-mimetic agent, while treatment with telmisartan restored them. This in line with other experiences showing that angiotensin II (ATII) exerts an inhibitory effect on Cnx43, KCNQ1 and Bcl-2 expression, and PPAR-γ agonism is effective in preventing the reduction in Cnx43 induced by ATII.…”

“…Ventricular H9c2 cells are a well‐known relevant cell model in the mimicking of IR injury: Being the closest cells to primary cardiomyocytes concerning their energy metabolism features, such as number and arrangements of mitochondria and presence of beta‐tubulin II, H9c2 cells are a simple validated and useful in vitro model for exploring the mechanisms driven by hypoxia/reoxygenation . These lead to the hydroxylase enzyme inactivation, hypoxia‐inducible factor HIF‐1α stabilization, ROS generation, apoptosis and increased Bax/Bcl‐2 ratio followed by activation of caspase‐3 cleavage …”

Propofol protects human cardiac cells against chemical hypoxiainduced injury by regulating the JNK signaling pathways

“…Propofol protects against CoCl 2 -induced cardiac cell apoptosis. CoCl 2 has been reported to induce apoptosis of rat cardiac H9C2 cells (22). Therefore, the present study used Annexin V/PI staining to investigate the apoptotic ratio of AC16 and HCM cells following different treatments (Fig.…”

Effects of Hypoxia on Oxidative Stress, Autophagy and Apoptosis in Cardiomyocytes

“…MTT was added at a final concentration of 25 mg/ml. After a 4-h incubation at 37˚C, the reaction was halted by adding 150 µl of dimethyl sulfoxide (DMSO), and the relative absorbance value (AV) was measured at 595 nm using a microplate reader [21]. Cell viability was calculated according to the AV and density of cells.…”