HSP27 Alleviates Cardiac Aging in Mice via a Mechanism Involving Antioxidation and Mitophagy Activation.
HSP27 Alleviates Cardiac Aging in Mice via a Mechanism Involving Antioxidation and Mitophagy Activation.
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HSP27 通过抗氧化和线粒体自噬激活机制减轻小鼠心脏衰老
DOI：
10.1155/2016/2586706
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发表时间：
2016
影响因子：
--
通讯作者：
Liu L
中科院分区：
文献类型：
--
作者：
Lin S;Wang Y;Zhang X;Kong Q;Li C;Li Y;Ding Z;Liu L
衰老性心功能不全是心脏衰老的一个显著特征。热休克蛋白27（HSP 27）保护心脏功能免受缺血或化学挑战。我们假设HSP27可以减缓心脏衰老。在实验中使用具有心脏特异性表达HSP 27基因的转基因（Tg）小鼠和野生型（WT）同窝出生的小鼠。超声心动图显示，与年轻WT小鼠相比，老年WT小鼠的心脏功能显着下降。与此形成鲜明对比的是，与年老的WT小鼠相比，年老的Tg小鼠中衰老诱导的心功能损害减弱。老年Tg小鼠心脏中的心脏老化标志物水平低于老年WT小鼠心脏。与老年WT心脏相比，老年Tg心脏间质纤维化程度较轻，活性氧和泛素结合蛋白含量较低。此外，老年Tg心脏表现出比老年WT心脏更低的LC3-II和p62积累。老年Tg心脏中的Atg13、Vps34和Rab7水平也高于老年WT心脏。此外，老年Tg心脏具有比老年WT心脏更高的PINK1和Parkin水平，表明线粒体自噬在老年Tg心脏中被激活。两者合计，HSP 27减轻心脏老化，这一行动涉及抗氧化和线粒体自噬激活。
Aging-induced cardiac dysfunction is a prominent feature of cardiac aging. Heat shock protein 27 (HSP27) protects cardiac function against ischemia or chemical challenge. We hypothesized that HSP27 attenuates cardiac aging. Transgenic (Tg) mice with cardiac-specific expression of the HSP27 gene and wild-type (WT) littermates were employed in the experiments. Echocardiography revealed a significant decline in the cardiac function of old WT mice compared with young WT mice. In striking contrast, the aging-induced impairment of cardiac function was attenuated in old Tg mice compared with old WT mice. Levels of cardiac aging markers were lower in old Tg mouse hearts than in old WT mouse hearts. Less interstitial fibrosis and lower contents of reactive oxygen species and ubiquitin-conjugated proteins were detected in old Tg hearts than in old WT hearts. Furthermore, old Tg hearts demonstrated lower accumulation of LC3-II and p62 than old WT hearts. Levels of Atg13, Vps34, and Rab7 were also higher in old Tg hearts than in old WT hearts. Additionally, old Tg hearts had higher levels of PINK1 and Parkin than old WT hearts, suggesting that mitophagy was activated in old Tg hearts. Taken together, HSP27 alleviated cardiac aging and this action involved antioxidation and mitophagy activation.