Adropin reduces hypoxia/reoxygenation-induced myocardial injury via the reperfusion injury salvage kinase pathway
Adropin reduces hypoxia/reoxygenation-induced myocardial injury via the reperfusion injury salvage kinase pathway
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DOI：
10.3892/etm.2019.7937
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发表时间：
2019-11-01
影响因子：
2.7
通讯作者：
Chen, Lianglong
中科院分区：
文献类型：
--
作者：
Wu, Lingzhen;Fang, Jun;Chen, Lianglong
Adropin是一种分泌性多肽，已被证明在保护血管内皮中起重要作用。促存活激酶（如PI 3 K-Akt和ERK 1/2）的药理学活化参与再灌注损伤补救激酶（RISK）途径。本研究观察了阿霉素对模拟缺血/再灌注（SI/R）心肌细胞损伤的影响。此外，目前的研究还评估了H9 c2成心肌细胞模型中控制SI/R的机制。使用MTT测定法测量细胞活力。使用肌酸激酶MB测量评估细胞损伤。采用流式细胞术和caspase-3活性评估细胞凋亡。使用肿瘤坏死因子α和白细胞介素-10表达来测量炎症反应。氧化应激采用丙二醛和超氧化物歧化酶进行评估。Western blot检测Akt、ERK 1/2、糖原合成酶激酶3 β（GSK 3 β）、Bcl-2和Bax的表达水平。本研究的结果显示，中等剂量的Adropin增加细胞活力，减少早期凋亡和caspase-3活性，促进Bcl-2表达，抑制Bax，增加Bcl-2/Bax比值。Adropin显著增加Akt、ERK 1/2和GSK 3 β的磷酸化，而PI 3 K和ERK 1/2的抑制剂LY 294002和PD 98059分别消除了Adropin的心脏保护作用。Adropin组和SI/R组的磷酸化STAT 3/总STAT 3表达无显著差异，Janus激酶2抑制剂AG 490对Adropin的保护作用无显著影响。这些结果表明，Adropin通过RISK途径而不是存活激活因子增强途径对SI/R损伤发挥保护作用。
Adropin is a secreted polypeptide that has been demonstrated to serve an important role in protecting the vascular endothelium. Pharmacological activation of pro-survival kinases, such as PI3K-Akt and ERK1/2, are involved in the reperfusion injury salvage kinase (RISK) pathway. In the present study, the effects of adropin in cardiomyocyte injury induced by simulated ischemia/reperfusion (SI/R) were assessed. Additionally, the current study also assessed the mechanisms that govern SI/R in a H9c2 cardiomyoblast cell model. Cell viability was measured using an MTT assay. Cell injury was assessed using creatine kinase MB measurements. Apoptosis was assessed using flow cytometry and caspase-3 activity. The inflammatory response was measured using tumor necrosis factor alpha and interleukin-10 expression. Oxidative stress was assessed using malondialdehyde and superoxide dismutase. The expression levels of Akt, ERK1/2, glycogen synthase kinase 3 beta (GSK3 beta), Bcl-2 and Bax were determined using western blot analysis. The results of the current study revealed that moderate-dose adropin increased cell viability, reduced early apoptosis and caspase-3 activity, promoted Bcl-2 expression, inhibited Bax and increased the Bcl-2/Bax ratio. Adropin significantly increased the phosphorylation of Akt, ERK1/2 and GSK3 beta, whereas inhibitors of PI3K and ERK1/2, respectively, LY294002 and PD98059, abolished the cardioprotective role of adropin. Furthermore, no significant difference was observed in phosphorylated-STAT3/total-STAT3 expression between the adropin and SI/R groups and Janus kinase 2 inhibitor AG490 did not significantly inhibit the protective role of adropin. These results indicate that adropin exerts a protective effect against SI/R injury through the RISK pathway instead of the survivor activating factor enhancement pathway.