PEX5 prevents cardiomyocyte hypertrophy via suppressing the redox-sensitive signaling pathways MAPKs and STAT3
PEX5 prevents cardiomyocyte hypertrophy via suppressing the redox-sensitive signaling pathways MAPKs and STAT3
复制标题
PEX5 通过抑制氧化还原敏感信号通路 MAPK 和 STAT3 来防止心肌细胞肥大
DOI：
10.1016/j.ejphar.2021.174283
复制
发表时间：
2021
影响因子：
5
通讯作者：
Liu Peiqing
中科院分区：
文献类型：
--
作者：
Wang Minghui;Li Jingyan;Ding Yanqing;Cai Sidong;Li Zhuoming;Liu Peiqing
过氧化物酶体生物发生因子5（PEX 5）是过氧化物酶体生物发生蛋白家族的成员，是过氧化物酶体基质蛋白转运的穿梭受体。PEX 5在心肌细胞肥大中的作用尚不清楚。我们的研究表明，PEX 5的蛋白表达水平下降，在原代新生大鼠心肌细胞与苯肾上腺素（PE）和心脏肥大大鼠的心脏腹主动脉缩窄（AAC）。PEX 5过表达可减轻PE诱导的心肌细胞肥大，而PEX 5沉默则加重心肌细胞肥大。PEX 5通过降低细胞活性氧水平和保护过氧化物酶体过氧化氢酶来改善氧化还原失衡。此外，PEX 5敲低加剧了PE诱导的氧化还原敏感信号通路的激活，包括丝裂原活化蛋白激酶（MAPK）通路和信号转导和转录激活因子3（STAT 3）;而PEX 5过表达抑制MAPK和STAT 3的激活。但PEX 5不影响PE诱导的哺乳动物雷帕霉素靶蛋白（mTOR）的磷酸化。总之，本研究表明，PEX 5通过调节氧化还原稳态和抑制氧化还原敏感的信号通路MAPK和STAT 3来保护心肌细胞免受肥大。
Peroxisomal biogenesis factor 5 (PEX5) is a member of peroxisome biogenesis protein family which serves as a shuttle receptor for the import of peroxisome matrix protein. The function of PEX5 on cardiomyocyte hypertrophy remained to be elucidated. Our study demonstrated that the protein expression level of PEX5 was declined in primary neonatal rat cardiomyocytes treated with phenylephrine (PE) and hearts from cardiac hypertrophic rats induced by abdominal aortic constriction (AAC). Overexpression of PEX5 alleviated cardiomyocyte hypertrophy induced by PE, while silencing of PEX5 exacerbated cardiomyocyte hypertrophy. PEX5 improved redox imbalance by decreasing cellular reactive oxygen species level and preserving peroxisomal catalase. Moreover, PEX5 knockdown aggravated PE-induced activation of redox-sensitive signaling pathways, including mitogen-activated protein kinase (MAPK) pathway and signal transducer and activator of transcription 3 (STAT3); whereas PEX5 overexpression suppressed activation of MAPK and STAT3. But PEX5 did not affect PE-induced phosphorylation of mammalian target of rapamycin (mTOR). In conclusion, the present study suggests that PEX5 protects cardiomyocyte against hypertrophy via regulating redox homeostasis and inhibiting redox-sensitive signaling pathways MAPK and STAT3.