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Histamine deficiency aggravates cardiac injury through miR-206/216b-Atg13 axis-mediated autophagic-dependant apoptosis.

ABSTRACT: 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.

SUBMITTER: Ding S

PROVIDER: S-EPMC5992227 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Histamine deficiency aggravates cardiac injury through miR-206/216b-Atg13 axis-mediated autophagic-dependant apoptosis.

Ding Suling S Abudupataer Mieradilijiang M Zhou Zheliang Z Chen Jinmiao J Li Hui H Xu Lili L Zhang Weiwei W Zhang Shuning S Zou Yunzeng Y Hong Tao T Wang Timothy C TC Yang Xiangdong X Ge Junbo J

Cell death & disease 20180607 6

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<sup>-/-</sup>), in which histamine is deficient. We also observed that autophagy was hi ...[more]

PMID: 29880830

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Histamine deficiency aggravates cardiac injury through miR-206/216b-Atg13 axis-mediated autophagic-dependant apoptosis.

Publications

Histamine deficiency aggravates cardiac injury through miR-206/216b-Atg13 axis-mediated autophagic-dependant apoptosis.

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