miR‑133b‑5p contributes to hypoxic preconditioning‑mediated cardioprotection by inhibiting the activation of caspase‑8 and caspase-3 in cardiomyocytes.
miR‑133b‑5p contributes to hypoxic preconditioning‑mediated cardioprotection by inhibiting the activation of caspase‑8 and caspase-3 in cardiomyocytes.
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DOI：
10.3892/mmr.2018.8784
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发表时间：
2018-05
影响因子：
3.4
通讯作者：
Chen ZW
中科院分区：
文献类型：
--
作者：
Pan YL;Han ZY;He SF;Yang W;Cheng J;Zhang Y;Chen ZW
在先前使用microRNA(miRNA/miR)微阵列分析的研究中，我们证明了miR-133b-5p在低氧预适应(HPC)时上调。本研究旨在探讨miR-133b-5p在HPC诱导的心肌保护中的作用及其与caspase-8和caspase-3凋亡信号转导的关系。成年大鼠心肌缺血/再灌注(I/R)损伤加或不加缺血预适应(IPC)，测定心肌miR-133b-5p水平。分离新生大鼠心肌细胞，进行缺氧/复氧(H/R)损伤，观察HPC对心肌细胞的影响。将miR-133b-5p反义寡核苷酸导入心肌细胞，观察其能否阻断HPC诱导的心肌保护作用。通过检测细胞存活率、乳酸脱氢酶(LDH)活性和凋亡率来评价细胞损伤程度。逆转录-定量聚合酶链式反应检测miR-133b-5p水平。用免疫印迹法检测caspase-8和caspase-3的活性，并用比色法检测切割片段。心肌I/R损伤后，miR-133b-5p在心肌中的表达减少，而IPC可恢复这种表达。HPC通过提高细胞存活率、减少乳酸脱氢酶释放和细胞凋亡来保护新生大鼠心肌细胞免受H/R损伤。这些保护作用与miR-133b-5p的上调有关。然而，心肌细胞miR-133b-5p的下调阻断了HPC介导的心肌保护作用，表现为细胞损伤和细胞凋亡的加重。Anagomir明显抑制HPC上调的miR-133b-5p水平。此外，caspase-8和caspase-3的切割和活性可被HPC抑制，而被miR-133b-5p敲除后则被逆转。MiR-133b-5p的上调有助于HPC介导的心肌保护作用，其机制可能与抑制caspase-8和caspase-3的凋亡信号有关。
In a previous study using a microRNA (miRNA/miR) microarray assay, we demonstrated that miR-133b-5p was upregulated in response to hypoxic preconditioning (HPC). The present study was designed to investigate the role of the miR-133b-5p in HPC-induced cardioprotection and the underlying mechanisms involving caspase-8 and caspase-3 apoptotic signaling. Adult rats were subjected to myocardial ischemia/reperfusion (I/R) injury with or without ischemic preconditioning (IPC), and the level of miR-133b-5p in myocardium was measured. Neonatal rat cardiomyocytes were isolated and subjected to hypoxia/reoxygenation (H/R) injury, with or without HPC. miR-133b-5p antagomir was transfected into the cardiomyocytes to observe whether it could block HPC-induced cardioprotection. Cellular injury was evaluated by detecting cell viability, lactate dehydrogenase (LDH) activity and apoptotic rate. Reverse transcription-quantitative polymerase chain reaction was used to measure the level of miR-133b-5p. The activation of caspase-8 and caspase-3 were measured by western blot analysis to detect the cleaved fragments as well as a colorimetric assay. Following myocardial I/R injury, the expression of miR-133b-5p was decreased in myocardium, while this decrease was restored by IPC. HPC protected neonatal rat cardiomyocytes against H/R injury by increasing cell viability, while reducing LDH release and cell apoptosis. These protective effects were coupled with the upregulation of miR-133b-5p. However, the knockdown of miR-133b-5p in the cardiomyocytes blocked HPC-mediated cardioprotection as reflected by the aggravation of cell injury and apoptosis. HPC upregulated miR-133b-5p level was markedly suppressed by the antagomir. In addition, the cleavage and activities of caspase-8 and caspase-3 were inhibited by HPC while reversed by knockdown of miR-133b-5p. Upregulation of miR-133b-5p contributes to HPC-mediated cardioprotection in cardiomyocytes, and the mechanism may be associated with inhibition of caspase-8 and caspase-3 apoptotic signaling.
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影响因子：
8
作者：
Engels, IH;Stepczynska, A;Wesselborg, S
通讯作者：
Wesselborg, S
影响因子：
37.8
作者：
Hoole, Stephen P.;Heck, Patrick M.;Dutka, David P.
通讯作者：
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影响因子：
4.6
作者：
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通讯作者：
Harashima H
DOI：
10.1152/ajpheart.00777.2002
发表时间：
2003-02-01
影响因子：
4.8
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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