MicroRNA-135a Regulates Apoptosis Induced by Hydrogen Peroxide in Rat Cardiomyoblast Cells

Abstract

Oxidative stress and apoptosis are the most important pathologic features of ischemic heart disease. Recent research has indicated that microRNAs (miRs) play an essential role in apoptosis. However, whether miRs might regulate B cell lymphoma-2 (Bcl-2) protein in apoptosis during ischemic heart disease is still unclear. The aim of this study, therefore, was to confirm the regulation of microRNA-135a (miR-135a) in oxidative stress injuries induced by hydrogen peroxide (H2O2) in rat cardiomyoblast cells H9c2. To this end, we analyzed the effects of H2O2 treatment on miR-135a expression in rat cardiomyocytes. Furthermore, we upregulated and inhibited miR-135a using mimics and inhibitors, respectively, and examined the effects on cell viability and apoptosis-related proteins. We observed that miR-135a was markedly up-regulated under H2O2 treatment in rat cardiomyoblast cells. Overexpression of miR-135a blocked the Bcl-2 protein and enhanced the apoptosis induced by H2O2, and miR-135a inhibition restored Bcl-2 protein expression. Interestingly, miR-135a inhibition did not attenuate H2O2-induced apoptosis with Bcl-2 knockdown. The results of the present study indicate that miR-135a regulates H2O2-induced apoptosis in H9c2 cells via targeting Bcl-2, and that miR-135a may be a novel therapeutic target for ischemic heart disease.

Blood levels of microRNAs associated with ischemic heart disease differ between Austrians and Japanese: a pilot study

“…Here we report three miRNAs, miR-135a, miR-451a and miR-486-5p, of which the blood expression levels have been reported to be positively associated with IHD 17 , 20 , 26 , 27 , to be prominently higher (fold change: miR-135a, 1.99; miR-451a, 3.03; miR-486-5p, 2.38) in Austrians than in Japanese. Regarding their pathophysiological significance, miR-135a has been reported to be involved in apoptosis of rat cardiomyoblast cells by down-regulating Bcl-2 35 . miR-486 has been suggested as related to cardiac hypertrophy: miR-486 up-regulation contributes to the activation of Bcl-2-related mitochondrial apoptotic pathways, thereby exhibiting an anti-apoptotic function in cardiomyocytes 36 .…”

“…Among twelve miRNAs, miR-135a, miR-486, miR-2861, and miR-150 are candidate miRNAs explaining the mechanisms for the difference in the incidence of IHD in Austrians and Japanese. miR-135a and miR-486 are involved in apoptosis of cardiomyocytes and cardiac hypertrophy 35 , 36 . miR-2861 regulates osteoblast differentiation and calcification 40 , which may suppress progression of atherosclerotic lesion.…”

Antioxidant Therapeutic Strategies for Cardiovascular Conditions Associated with Oxidative Stress

“…These studies show that miRNAs are modulated by antioxidant compounds and ROS, however they also can be involved in ROS production. For example miR-135a participates in the regulation of H 2 O 2 -mediated apoptosis in embryonic rat cardiac myoblast cell lines ([ 92 ], Liu, Shi et al, 2017]). A study in an animal model revealed that miR-133a via targeting uncoupling protein 2 (UCP2) participates in inflammatory bowel disease by altering downstream inflammation, oxidative stress and markers of energy metabolism ([ 93 ], Jin, Chen et al, 2017).…”

Molecular expression and functional analysis of genes in children with temporal lobe epilepsy

“…Similarly, miR-135a-5p plays a key role on apoptosis in ovarian cancer cells (Tang et al, 2013). Furthermore, miR-135a-5p enhances hydrogen peroxide-induced apoptosis in rat cardiomyoblast (Liu et al, 2017). Additionally, inhibition of miR-135a-5p protects A549 cells from apoptosis (Zhao et al, 2014).…”

“…Both of these pathways have been found to be triggered in TLE (Henshall, 2007). However, several studies have demonstrated that miR-135a-5p is solely involved in a mitochondria-dependent apoptosis pathway (Wu et al, 2012;Liu et al, 2017;Zhao et al, 2014), which suggests miR-135a-5p could regulate the intrinsic pathway of apoptosis in children with TLE. Although previous studies have shown that miR-135a-5p initiates apoptosis by downregulating expression of pro-apoptotic Bcl-2 family members, including Bcl-2 and Bcl-xL (Zhao et al, 2014;Navarro et al, 2009), a novel target gene of miR-135a-5p was identified in this study and its expressed protein is also an anti-apoptotic protein.…”