Beclin-1 improves mitochondria-associated membranes in the heart during endotoxemia.
Beclin-1 improves mitochondria-associated membranes in the heart during endotoxemia.
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Beclin-1在内毒素血症期间改善心脏中的血管相关膜。
DOI：
10.1096/fba.2020-00039
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发表时间：
2021-03
影响因子：
2.7
通讯作者：
Zang QS
中科院分区：
文献类型：
--
作者：
Sun Y;Cai Y;Qian S;Chiou H;Zang QS
线粒体相关膜(MAM)是线粒体的重要组成部分。本研究旨在确定内毒素血症是否会重排心脏中的MAM，以及Beclin-1是否调节这一过程。野生型小鼠和心脏特异性Beclin-1过表达(Becn1-TG)或Beclin-1杂合子敲除(Becn1+/−)的小鼠接受内毒素攻击。在心脏组织中，用电子显微镜观察MAM的超微结构，用免疫组织化学方法评价其组织学。采用超速离心法分离MAM，并对其含量和功能进行定量测定。同时观察Beclin-1激活肽(TB-肽)对MAM的作用。数据显示，内毒素血症使MAM的总质量和功能均下降，在Becn1+/−小鼠中，这些缺陷加重，但在Becn1-TG和TB多肽处理的小鼠中，这些缺陷得到缓解。此外，还观察了AC16人心肌细胞对脂多糖和TB多肽的反应。体外实验结果显示，脂多糖和TB-肽对心肌细胞的作用是一致的；LPS的攻击降低了MAM的水平和活性，而TB-肽可减轻这一缺陷。综上所述，这些结果表明Beclin-1在内毒素血症时改善心脏MAM方面具有新的功能，为先前确定的Beclin-1在保护线粒体和心功能方面的作用提供了机制。
Mitochondria‐associated membranes (MAMs) are essential to mitochondria. This study was to determine whether endotoxemia rearranges MAMs in the heart, and whether Beclin‐1 regulates this process. Wild‐type mice and mice with a cardiac‐specific overexpression of Beclin‐1 (Becn1‐Tg), or a heterozygous knockout of Beclin‐1 (Becn1 +/−) were given lipopolysaccharide (LPS) challenge. In the heart, the ultrastructure of MAMs was examined by electron microscopy and the histology evaluated by immunostaining. Additionally, MAMs were isolated by ultracentrifugation, and their content and function were quantified. The effects of Beclin‐1‐activating peptide (TB‐peptide) on MAMs were also examined. Data showed that endotoxemia decreased both the total mass and the function of MAMs, and these deficiencies became worse in Becn1 +/− mice but were alleviated in Becn1‐Tg and TB‐peptide‐treated mice. Responses of myocardial MAMs to LPS and to TB‐peptide were additionally examined in AC16 human cardiomyocytes. In vitro findings recaptured the effects of LPS and TB‐peptide in cardiomyocytes; the challenge of LPS reduced the level and activity of MAMs, and TB‐peptide attenuated this defect. Together, the results suggest a new function of Beclin‐1 in improving cardiac MAMs during endotoxemia, providing a mechanism for the previously identified role of Beclin‐1 in protection of mitochondria and cardiac function.
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