Survival motor neuron protein protects H9c2 cardiomyocytes from hypoxia-induced cell injury by reducing apoptosis.

Abstract

Hypoxia induces cell injury in cardiomyocytes and leads to the development of cardiovascular diseases. The survival motor neuron protein (SMN) is a crucial ubiquitous protein whose functional deficiency causes motor neuron loss seen in spinal muscular atrophy. SMN has shown protective effects on the cardiovascular system and the aim of the present study was to investigate the cardioprotective effects of SMN on hypoxia-induced cell injury. Cobalt chloride (CoCl2 ) was used to induce chemical hypoxia in H9c2 cardiomyocytes. Cell proliferation was determined by the MTT assay and the mRNA levels of SMN were evaluated by real-time polymerase chain reaction. The protein expression levels of SMN, hypoxia-inducible transcription factor 1α (HIF-1α), and apoptosis-related proteins, such as cytochrome c (Cyt c), B cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), and cleaved caspase-3 were evaluated by western blot analysis. Cell apoptosis was analysed using annexin V/propidium iodide (PI) staining. Treatment with CoCl2 significantly reduced H9c2 cell viability; the level of HIF-1α, which is a hypoxia-related indicator increased whereas the expression of SMN protein decreased. Hypoxia also induced cardiomyocyte apoptosis, indicated by reduced Bcl-2 expression and elevated cleaved caspase-3, Bax, and cytochrome c levels. Interestingly, SMN, which is a neuron protection factor, ameliorated CoCl2 -induced cell damage by reducing cardiomyocyte apoptosis through upregulation of Bcl-2 and inhibition of cytochrome c, cleaved caspase-3, and Bax expression. Survival motor neuron prevents hypoxia-induced cell apoptosis through inhibition of the mitochondrial apoptotic pathway, and thereby exerts a protective effect on H9c2 cardiomyocytes.