Inducible nitric oxide synthase and cyclooxgenase-2 mediate protection of hydrogen peroxide preconditioning against apoptosis induced by oxidative stress in PC12 cells.
The induction of inducible nitric oxide synthase (iNOS) in response to different stress is associated with simultaneous induction of cyclooxygenase-2 (COX-2) in various cell types. Both iNOS and COX-2 have been reported to mediate the late phase of cardioprotection induced by different preconditioning. However, whether both iNOS and COX-2 are mediators in the neuroprotection induced by preconditioning with hydrogen peroxide (H(2)O(2)) at low concentration is unknown. In this study, using the neurosecretory cell line-PC12 cells to set up the model of neuroprotection of preconditioning with H(2)O(2) against apoptosis, we first investigate what changes in expression of iNOS and COX-2 appear during H(2)O(2) preconditioning, then determine if both iNOS inhibitor and COX-2 inhibitor interfere with the neuroprotection elicited by preconditioning with H(2)O(2). We found that preconditioning with H(2)O(2) at 10 microM significantly protected PC12 cells against apoptosis induced by lethal H(2)O(2) (50 microM) and increased the expression of iNOS and COX-2 and that selective iNOS inhibitor, aminoguanidine (AG) and COX-2 inhibitor, NS-398 obviously blocked the protective effects induced by preconditioning with 10 microM H(2)O(2). The results of this study suggest that both iNOS and COX-2 are mediators of the neuroprotection induced by preconditioning with oxidative stress (H(2)O(2) at low concentration) in PC12 cells.
Tang
Xiao-qing
XQ
Department of Physiology, Zhongshan Medical College, Sun Yat-sen University, Guangzhou, 510080, PR China.
Yu
Hui-min
HM
Zhi
Jun-li
JL
Cui
Yu
Y
Tang
Er-hu
EH
Feng
Jian-qiang
JQ
Chen
Pei-xi
PX
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002467:Cell Nucleus / Q000648:ultrastructure; D002470:Cell Survival / Q000502:physiology; D004396:Coloring Agents; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D009578:Nitrobenzenes / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology*; D016716:PC12 Cells; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology
D004396:Coloring Agents; D052246:Cyclooxygenase 2 Inhibitors; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D006861:Hydrogen Peroxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2