Histamine deficiency aggravates cardiac injury through miR-206/216b-Atg13 axis-mediated autophagic-dependant apoptosis.
Histamine deficiency aggravates cardiac injury through miR-206/216b-Atg13 axis-mediated autophagic-dependant apoptosis.
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组胺缺乏通过 miR-206/216b-Atg13 轴介导的自噬依赖性细胞凋亡加重心脏损伤
DOI：
10.1038/s41419-018-0723-6
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发表时间：
2018-06-07
影响因子：
9
通讯作者：
Ge J
中科院分区：
文献类型：
--
作者：
Ding S;Abudupataer M;Zhou Z;Chen J;Li H;Xu L;Zhang W;Zhang S;Zou Y;Hong T;Wang TC;Yang X;Ge J
组胺是一种广泛分布的生物胺，参与一系列生物过程的调节。血清组胺水平在急性心肌梗死早期明显升高，但其作用尚不清楚。组氨酸脱羧酶(HDC)是唯一负责组胺产生的酶，组胺缺乏的HDC基因敲除小鼠(hDC−/−)心脏损伤明显加重。我们还观察到−/−小鼠在急性心肌梗死后心肌细胞自噬被高度激活，这种自噬被外源性组胺的代偿所消除。体内和体外实验结果表明，组胺通过组胺1受体作用，增加miR-206和miR-216B，协同作用靶向Atg13，从而减少缺氧和急性心肌梗死条件下自噬的激活。进一步的研究表明，Atg13与FADD相互作用，促进caspase-8的激活和细胞的凋亡。综上所述，这些数据揭示了一个新的细胞内信号通路，它参与了组胺调节缺氧和急性心肌梗死条件下的心肌自噬和凋亡，这可能有助于更全面地评价组胺受体拮抗剂的使用，并开发新的心肌梗死治疗靶点。
Histamine is a widely distributed biogenic amine involved in the regulation of an array of biological processes. Serum histamine level is markedly elevated in the early stages of acute myocardial infarction, whereas the role it plays remains unclear. Histidine decarboxylase (HDC) is the unique enzyme responsible for histamine production, and cardiac injury is significantly aggravated in HDC knockout mice (HDC−/−), in which histamine is deficient. We also observed that autophagy was highly activated in cardiomyocytes of HDC−/−mice post acute myocardial infarction (AMI), which was abolished by compensation of exogenous histamine. The in vivo and in vitro results showed that acting through histamine 1 receptor, histamine increased miR-206 and miR-216b, which worked in concert to target to Atg13, resulting in the reduction of autophagy activation under hypoxia and AMI condition. Further study revealed that Atg13 interacted with FADD to promote the activation of caspase-8 and cell apoptosis. Taken together, these data unveil a novel intracellular signaling pathway involved in histamine regulating myocardial autophagy and apoptosis under hypoxia and AMI condition, which might help to more comprehensively evaluate the usage of histamine receptor antagonists and to develop new therapeutic targets for myocardial infarction.
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影响因子：
37.8
作者：
Chen J;Hsieh AF;Dharmarajan K;Masoudi FA;Krumholz HM
通讯作者：
Krumholz HM
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影响因子：
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作者：
Chhabra R;Adlakha YK;Hariharan M;Scaria V;Saini N
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影响因子：
20.1
作者：
Gustafsson AB;Gottlieb RA
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Gottlieb RA
影响因子：
5.4
作者：
Jiang, Hong;White, Erin J.;Fueyo, Juan
通讯作者：
Fueyo, Juan
影响因子：
2.9
作者：
Adachi, N;Liu, K;Arai, T
通讯作者：
Arai, T