Role of the JAK-STAT pathway in protection of hydrogen peroxide preconditioning against apoptosis induced by oxidative stress in PC12 cells.
The aim of this study was to investigate the role of JAK-STAT pathway in the cytoprotection afforded by preconditioning with H(2)O(2). It was shown that (1) Preconditioning with 100 micromol/L H(2)O(2) can markedly protect PC12 cells against apoptosis and cytotoxicity induced by 300 micromol/L H(2)O(2); (2) The expression and tyrosine phosphorylation of JAK2, not JAK1 were rapidly increased at 5 min after H(2)O(2) preconditioning; (3) The expression of STAT1 and STAT3 were significantly increased at 15 min after H(2)O(2) preconditioning, and the pTyr-STAT1 and pTyr-STAT3 were markedly increased at 60 min after H(2)O(2) preconditioning; (4) Pretreatment with the JAK inhibitor AG-490 (10 micromol/L) 20 min before H(2)O(2) preconditioning blocked not only the activation of JAK2, STAT1 and STAT3, but also the cytoprotection of H(2)O(2) preconditioning against apoptosis and cytotoxicity induced by oxidative stress. These findings suggested that preconditioning with H(2)O(2) activated the JAK-STAT pathway that played an important role in the cytoprotection induced by H(2)O(2) preconditioning.
Department of Physiology, Zhongshan Medical College, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou, 510080, People's Republic of China.
H M
HM
Yu
J L
JL
Zhi
Y
Y
Cui
E H
EH
Tang
S N
SN
Sun
J Q
JQ
Feng
P X
PX
Chen
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D019194:Ischemic Preconditioning; D018384:Oxidative Stress / Q000502:physiology*; D016716:PC12 Cells; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D051381:Rats; D050791:STAT Transcription Factors / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D050791:STAT Transcription Factors; D006861:Hydrogen Peroxide; D011505:Protein-Tyrosine Kinases