SENP3 protects H9C2 cells from apoptosis triggered by H/R via STAT3 pathway.

SENP3 protects H9C2 cells from apoptosis triggered by H/R via STAT3 pathway.
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DOI:
10.26355/eurrev_201805_14975
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发表时间:
2018-05
影响因子:
3.3
通讯作者:
Yijian Zhang;Zheng Lm;Wang Cx;Gu Jm;S. Xue
Yijian Zhang;Zheng Lm;Wang Cx;Gu Jm;S. Xue
中科院分区:
医学4区
文献类型:
--
作者:
Yijian Zhang;Zheng Lm;Wang Cx;Gu Jm;S. Xue

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目的 探讨SENP3是否通过信号转导和转录激活子3(STAT3)通路保护H/R引发的H9C2细胞凋亡。材料与方法 培养雄性C57BL小鼠,建立小鼠心肌I/RI模型。同时培养大鼠胚胎成肌细胞H9C2细胞系。使用 2',7'-二氯荧光素二乙酸酯 (DCFH) 试剂盒在 H/R 过程中检测活性氧 (ROS) 水平。通过流式细胞术检查凋亡细胞。采用Western blotting和逆转录聚合酶链反应(RT-PCR)检测p-JAK2、JAK2、STAT3、p-STAT3、cleaved-caspase3(c-caspase3)和Bcl/Bax的表达。结果我们发现,I/R 组小鼠和 H/R 后的 H9C2 细胞中 SENP3 升高,p-STAT3 增加。此外,SENP3 表达的增加被发现依赖于 ROS 的产生,因为 SENP3 的积累受到抗氧化剂 (NAC) 的抑制。抑制 SENP3 可抑制 p-STAT3 表达,但促进细胞凋亡、c-caspase3 表达和 Bcl/Bax 比值。此外,SENP3过表达可减轻细胞凋亡,但AG490可消除细胞凋亡。结论 SENP3可以通过增强JAK2/STAT3通路来保护H9C2免受H/R的影响。
OBJECTIVE To investigate whether SENP3 protects H9C2 cells from apoptosis triggered by H/R through the signal transducer and activator of transcription 3 (STAT3) pathway. MATERIALS AND METHODS Male C57BL mice were cultured and mouse models of myocardial I/RI were established. At the same time, cardiomyoblast H9C2 cell line of rat embryo was cultured. Reactive oxygen species (ROS) level was detected during H/R using 2',7'-dichlorofluorescein diacetate (DCFH) kit. Apoptotic cells were checked by flow cytometry. The expressions of p-JAK2, JAK2, STAT3, p-STAT3, cleaved-caspase3 (c-caspase3), and Bcl/Bax were detected using Western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS We revealed that SENP3 rose in mice of I/R group and in H9C2 cells following H/R with an increase in p-STAT3. Furthermore, increased expression of SENP3 was found to be dependent on the generation of ROS, as the SENP3 accumulation was inhibited by antioxidant (NAC). Inhibition of SENP3 suppressed the p-STAT3 expression, but promoted cell apoptosis, c-caspase3 expression, and Bcl/Bax ratio. Besides, SENP3 overexpression alleviated the cell apoptosis, which was abrogated by AG490. CONCLUSIONS SENP3 could protect H9C2 against H/R through enhancing JAK2/STAT3 pathway.