Yang Zheng, Liu Yuan, Deng Wei, Dai Jia, Li Fangfang, Yuan Yuan, Wu Qingqing, Zhou Heng, Bian Zhouyan, Tang Qizhu
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Mol Med Rep. 2014 May;9(5):1941-6. doi: 10.3892/mmr.2014.2002. Epub 2014 Mar 4.
Apoptosis is closely associated with the occurrence and development of cardiovascular diseases and is considered as one of the crucial pathological processes of cardiomyopathy, sepsis, ischemia/reperfusion injury, myocardial infarction and heart failure. Hesperetin (HES), a flavanone glycoside found in citrus fruit peels, has been known to exhibit several key biological and pharmacological properties. Previous studies have demonstrated the anti-inflammatory, anti-oxidant and anti-tumor functions of HES. However, with regards to the pro- or anti-apoptotic functions of HES, there are several disagreements within the literature. To examine whether HES has protective effects in cardiac apoptosis, the present study examined the role of HES in lipopolysaccharide (LPS)-stimulated H9C2 cardiomyocytes, aiming to clarify the possible mechanisms underlying its effects. In the present study, HES reduced the percentage of viable apoptotic (VA) cells in a flow cytometry analysis. It had an anti-apoptosis function in LPS-stimulated H9C2 cells. To clarify whether HES alleviated LPS-stimulated apoptosis through the mitochondria-dependent intrinsic apoptotic pathway, certain indicators of this pathway were detected, including members of the caspase family. The data revealed that HES attenuated the activation of capase-3 and caspase-9. These results indicated HES has a mitochondria-dependent anti-apoptosis effect in LPS-stimulated H9C2 cells. To explore the possible mechanisms, the protein expression levels of certain markers in the possible signaling pathway were detected, including JNK and Bcl-2 family. As a result, HES downregulated the protein expression of Bax, upregulated the expression of Bcl-2 and attenuated the phosphorylation level of JNK. Therefore, the anti-apoptosis effects of HES were possibly mediated by the JNK/Bax signaling pathway. In conclusion, HES has a mitochondria-dependent anti-apoptosis effect in LPS-induced H9C2 cells via the JNK/Bax signaling pathway.
细胞凋亡与心血管疾病的发生和发展密切相关，被认为是心肌病、脓毒症、缺血/再灌注损伤、心肌梗死和心力衰竭的关键病理过程之一。橙皮素（HES）是一种存在于柑橘类果皮中的黄酮糖苷，已知具有多种关键的生物学和药理学特性。先前的研究已经证明了HES的抗炎、抗氧化和抗肿瘤功能。然而，关于HES的促凋亡或抗凋亡功能，文献中存在一些分歧。为了研究HES是否对心脏细胞凋亡具有保护作用，本研究检测了HES在脂多糖（LPS）刺激的H9C2心肌细胞中的作用，旨在阐明其作用的潜在机制。在本研究中，流式细胞术分析显示HES降低了存活凋亡（VA）细胞的百分比。它在LPS刺激的H9C2细胞中具有抗凋亡功能。为了阐明HES是否通过线粒体依赖性内源性凋亡途径减轻LPS刺激的细胞凋亡，检测了该途径的某些指标，包括半胱天冬酶家族成员。数据显示HES减弱了半胱天冬酶-3和半胱天冬酶-9的激活。这些结果表明HES在LPS刺激的H9C2细胞中具有线粒体依赖性抗凋亡作用。为了探索可能的机制，检测了可能信号通路中某些标志物的蛋白表达水平，包括JNK和Bcl-2家族。结果，HES下调了Bax的蛋白表达，上调了Bcl-2的表达，并减弱了JNK的磷酸化水平。因此，HES的抗凋亡作用可能是由JNK/Bax信号通路介导的。总之，HES通过JNK/Bax信号通路在LPS诱导的H9C2细胞中具有线粒体依赖性抗凋亡作用。
