Jak2激酶抑制对ATP耗竭/恢复诱导的肾小管上皮细胞Stat1和Stat3激活及凋亡的影响。
Effect of Jak2 kinase inhibition on Stat1 and Stat3 activation and apoptosis of tubular epithelial cells induced by ATP depletion/recovery.
作者信息
Wang Jianzhong, Ouyang Chun, Chen Xiangmei, Fu Bo, Lu Yang, Hong Quan
机构信息
Kidney Institute and Key Laboratory of Chinese PLA, Department of Nephrology, General Hospital of Chinese PLA, Beijing - PR China.
出版信息
J Nephrol. 2008 Nov-Dec;21(6):919-23.
BACKGROUND
Apoptosis is involved in acute renal failure (ARF). Its exact mechanism still remains to be explored. The Jak-Stat pathway participates in inflammation, apoptosis and tumorigenesis. In an in vitro model of renal ischemia/reperfusion injury (IRI), we investigated the role of Jak2 kinase inhibition on signal transducer and activator of transcription 1 (Stat1) and Stat3 activations as well as apoptosis of human proximal tubular epithelial cells (HKCs) induced by adenosine triphosphate (ATP) depletion/recovery.
METHODS
ATP depletion of HKCs is induced by antimycin A.
RESULTS
The Jak2-specific inhibitor AG490 decreased Stat1 and Stat3 phosphorylations and promoted HKC apoptosis induced by ATP depletion/recovery.
CONCLUSIONS
Our results have demonstrated that Jak2 inhibition participated in the ATP depletion-induced apoptosis of HKCs, which might be a potential target for prevention and treatment of ARF.
背景
细胞凋亡与急性肾衰竭（ARF）有关。其确切机制仍有待探索。Jak-Stat信号通路参与炎症、细胞凋亡和肿瘤发生。在肾缺血/再灌注损伤（IRI）的体外模型中，我们研究了Jak2激酶抑制对信号转导子和转录激活子1（Stat1）和Stat3激活以及三磷酸腺苷（ATP）耗竭/恢复诱导的人近端肾小管上皮细胞（HKCs）凋亡的作用。
方法
用抗霉素A诱导HKCs的ATP耗竭。
结果
Jak2特异性抑制剂AG490降低了Stat1和Stat3的磷酸化，并促进了ATP耗竭/恢复诱导的HKC凋亡。
结论
我们的结果表明，Jak2抑制参与了ATP耗竭诱导的HKCs凋亡，这可能是ARF防治的潜在靶点。
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