Abstract
Rutin is a flavonoid with antioxidant property. It has been shown to exert cardioprotection against cardiomyocyte hypertrophy. However, studies regarding its antihypertrophic property are still lacking, whether it demonstrates similar antihypertrophic effect to its metabolite, quercetin. Hence, this study aimed to investigate the effects of both flavonoids on oxidative stress and mitogen-activated protein kinase (MAPK) pathway in H9c2 cardiomyocytes that were exposed to angiotensin II (Ang II) to induce hypertrophy. Cardiomyocytes were exposed to Ang II (600 nM) with or without quercetin (331 μM) or rutin (50 μM) for 24 h. A group given vehicle served as the control. The concentration of the flavonoids was chosen based on the reported effective concentration to reduce cell hypertrophy or cardiac injury in H9c2 cells. Exposure to Ang II increased cell surface area, intracellular superoxide anion level, NADPH oxidase and inducible nitric oxide synthase activities, and reduced cellular superoxide dismutase activity and nitrite level, which were similarly reversed by both rutin and quercetin. Rutin had no significant effects on phosphorylated proteins of extracellular signal-related kinases (ERK1/2) and p38 but downregulated phosphorylated c-Jun N-terminal kinases (JNK1/2), which were induced by Ang II. Quercetin, on the other hand, had significantly downregulated the phosphorylated proteins of ERK1/2, p38, and JNK1/2. The quercetin inhibitory effect on JNK1/2 was stronger than the rutin. In conclusion, both flavonoids afford similar protective effects against Ang II-induced cardiomyocyte hypertrophy, but they differently modulate MAPK pathway.
Highlights
Cardiac hypertrophy is commonly manifested in heart failure [1]
mitogenactivated protein kinase (MAPK) are a group of serine and threonine protein kinases that are encoded by multiple genes
angiotensin II (Ang II) increased the cellular B-type natriuretic peptide (BNP) level starting from 0.6 μM concentrations (p < 0.05) (Figure 1c), confirming that Ang II successfully induced cardiomyocyte hypertrophy
Summary
Cardiac hypertrophy is commonly manifested in heart failure [1]. Neurohormonal system activation is involved in the development of cardiac hypertrophy, with angiotensinII (Ang II) being the key player in inducing cardiomyocyte hypertrophy. Cardiac hypertrophy is commonly manifested in heart failure [1]. Neurohormonal system activation is involved in the development of cardiac hypertrophy, with angiotensin. II (Ang II) being the key player in inducing cardiomyocyte hypertrophy. Cardiomyocytes respond to Ang II by initiating several cascades that lead to hypertrophy [2]. The binding of Ang II on angiotensin type 1 receptor (AT1R), a G-protein-coupled receptor (GPCRs), causes the dissociation of different G-proteins that activate several signaling kinases and phosphatases including mitogen-activated protein kinases (MAPKs) [2]. MAPKs are a group of serine and threonine protein kinases that are encoded by multiple genes. Extracellular signal-related kinases (ERK1/2), c-Jun N-terminal kinases (JNK1/2), and p38 kinase (p38) are three MAPKs that have been reported to be involved in cardiac hypertrophy [3]
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