Acute alcohol intoxication enhances myocardial eIF4G phosphorylation despite reducing mTOR signaling.
Acute alcohol intoxication enhances myocardial eIF4G phosphorylation despite reducing mTOR signaling.
复制标题
尽管减少了 mTOR 信号传导，但急性酒精中毒仍会增强心肌 eIF4G 磷酸化。
DOI：
10.1152/ajpheart.00440.2004
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Goodman,StacyA
中科院分区：
文献类型：
--
作者：
Vary,ThomasC;Deiter,Gina;Goodman,StacyA
急性酒精中毒损害大鼠心肌蛋白质合成，继发于mRNA翻译效率降低。通过改变肽链起始的调节，mRNA翻译效率降低。本实验的目的是确定急性酒精中毒是否改变心脏中真核起始因子（eIF）4G的磷酸化状态、eIF 4G·eIF 4 E复合物的形成以及哺乳动物雷帕霉素靶蛋白（mTOR）信号通路。通过注射酒精（75 mmol/kg体重ip）诱导急性酒精中毒。对照组动物接受等体积的生理盐水。酒精给药增强eIF 4G（Ser 1108）的磷酸化约三倍。给予酒精可使活性eIF 4G·eIF 4 E复合物的形成降低> 90%，而使非活性4 E结合蛋白1（4 E-BP 1）·eIF 4 E复合物的丰度增加约160%。mTOR在Ser 2448和Ser 2481上的磷酸化降低了50%。mTOR磷酸化的减少不是由于PKB磷酸化的减少。急性酒精给药后，mTOR下游靶点4 E-BP 1和S6激酶1（Thr 389）的磷酸化也减少。这些数据表明，急性酒精诱导的心肌mRNA翻译起始损伤部分是由于eIF 4G·eIF 4 E复合物形成的显著减少，这似乎与eIF 4G磷酸化的变化无关，但依赖于mTOR。
Acute alcohol intoxication impairs myocardial protein synthesis in rats, secondary to a diminished mRNA translational efficiency. Decreased mRNA translational efficiency occurs through altered regulation of peptide chain initiation. The purpose of the present set of experiments was to determine whether acute alcohol intoxication alters the phosphorylation state of eukaryotic initiation factor (eIF) 4G, eIF4G·eIF4E complex formation, and the mammalian target of rapamycin (mTOR) signaling pathway in the heart. Acute alcohol intoxication was induced by injection of alcohol (75 mmol/kg body wt ip). Control animals received an equal volume of saline. Alcohol administration enhanced phosphorylation of eIF4G (Ser1108) approximately threefold. Alcohol administration lowered formation of the active eIF4G·eIF4E complex by >90%, whereas it increased the abundance of the inactive 4E-binding protein 1 (4E-BP1)·eIF4E complex by ∼160%. Phosphorylation of mTOR on Ser2448and Ser2481was decreased by 50%. Reduced mTOR phosphorylation did not result from decreased phosphorylation of PKB. Phosphorylation of 4E-BP1 and S6 kinase 1 (Thr389), downstream targets of mTOR, were also reduced after acute alcohol administration. These data suggest that acute alcohol-induced impairments in myocardial mRNA translation initiation result, in part, from marked decreases in eIF4G·eIF4E complex formation, which appear to be independent of changes in phosphorylation of eIF4G but dependent on mTOR.
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作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1007/s12144-021-02198-1
发表时间：
2023
期刊：
Current psychology (New Brunswick, N.J.)
影响因子：
--
作者：
Ahadzadeh AS;Ong FS;Wu SL
通讯作者：
Wu SL
影响因子：
4.2
作者：
Anthony, JC;Anthony, TG;Jefferson, LS
通讯作者：
Jefferson, LS