Metabolic adaptive ALT isoenzyme response in livers of C57/BL6 mice treated with dexamethasone.
Metabolic adaptive ALT isoenzyme response in livers of C57/BL6 mice treated with dexamethasone.
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DOI：
10.1177/0192623312447550
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发表时间：
2012-12
影响因子：
1.5
通讯作者：
Gong DW
中科院分区：
文献类型：
--
作者：
Reagan WJ;Yang RZ;Park S;Goldstein R;Brees D;Gong DW
丙氨酸氨基转移酶（ALT）被用作肝细胞损伤的指标。由于ALT由两种同工酶组成，因此更好地了解ALT同工酶生物学对引起代谢适应性反应与肝毒性反应的化合物的反应，将有助于更准确地评估ALT升高的意义。本研究的目的是描述用25或75 mg/kg地塞米松处理小鼠24或72小时的ALT同工酶反应，已知地塞米松可诱导促排异反应状态。用75 mg/kg地塞米松处理小鼠72小时显示总肝脏ALT活性增加。蛋白质印迹显示，在两个剂量和时间点ALT 2均增加，并且在24和72小时ALT 2核糖核酸同时增加。通过活性测定评估的ALT同工酶反应显示ALT 2增加。肝脏ALT升高与肝糖原升高相关，无肝细胞坏死。血清总ALT活性增加，但未评价血清同工酶。因此，作者证明地塞米松诱导肝脏和血清ALT升高，这反映了肝细胞促肝细胞生成代谢适应性反应。
Alanine aminotransferase (ALT) is used as an indicator of hepatocellular injury. Since ALT consists of two isoenzymes, a better understanding of ALT isoenzyme biology in response to compounds that cause metabolic adaptive versus hepatotoxic responses will allow for a more accurate assessment of the significance of an ALT increase. The purpose of this study was to characterize the ALT isoenzyme response in mice treated with 25 or 75 mg/kg of dexamethasone, which is known to induce a progluconeogenic state, for 24 or 72 hr. Those mice treated with 75 mg/kg for 72 hr showed an increase in total liver ALT activity. Western blot showed that there was an increase in ALT2 at both doses and time points and there was a concurrent increase in ALT2 ribonucleic acid at 24 and 72 hr. The ALT isoenzyme response assessed by an activity assay showed an increase in ALT2. The increases in liver ALT were associated with an increase in liver glycogen and there was no hepatocellular necrosis. There was an increase in total serum ALT activity, although serum isoenzymes were not evaluated. Thus, the authors demonstrated that dexamethasone induced increases in hepatic and serum ALT, which reflect a hepatocellular progluconeogenic metabolic adaptive response.