Effect of Jak2 kinase inhibition on Stat1 and Stat3 activation and apoptosis of tubular epithelial cells induced by ATP depletion/recovery.
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.
Wang
Jianzhong
J
Kidney Institute and Key Laboratory of Chinese PLA, Department of Nephrology, General Hospital of Chinese PLA, Beijing - PR China.
Ouyang
Chun
C
Chen
Xiangmei
X
Fu
Bo
B
Lu
Yang
Y
Hong
Quan
Q
D000255:Adenosine Triphosphate / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors*; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000473:pathology; D050794:STAT1 Transcription Factor / Q000187:drug effects / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000187:drug effects / Q000378:metabolism*; D020032:Tyrphostins / Q000494:pharmacology
D004791:Enzyme Inhibitors; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D000255:Adenosine Triphosphate; D053614:Janus Kinase 2