Acta Pharmacologica Sinica 2007 August; 28 (8): 1123-1128; doi: 10.1111/j.1745-7254.2007.00610.x

Acta Pharmacologica Sinica 2007 August; 28 (8): 1123-1128; doi: 10.1111/j.1745-7254.2007.00610.x

Original Article

Propofol attenuates oxidative stress-induced PC12 cell injury via p38 MAP kinase dependent pathway¹

Xing-jun WU², Yong-jun ZHENG³, Yong-yao CUI², Liang ZHU², Yang LU^2,4, Hong-zhuan CHEN^2,4

²Department of Pharmacy, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; ³Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China

Aim: To investigate the neuroprotective effect of propofol and its intracellular mechanism on neurons in vitro.

Methods: Cell viability was determined with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide reduction. Apoptotic cell death was determined by Hoechst 33258 staining and a fluorescence-activated cell sorter. The caspase-3 activity was measured by fluorometric assay. Mitogen-activated protein (MAP) kinase phosphorylation was detected with Western blotting.

Results: The pretreatment of rat pheochromocytoma cell line PC12 with propofol (1_10 µmol/L) resulted in a significant recovery from hydrogen peroxide (H₂O₂)-induced cell death and the inhibition of H₂O₂ induced caspase-3 activation and PC12 cell apoptosis. Propofol inhibited the H₂O₂-induced p38 MAP kinase, but not c-Jun N-terminal kinase or extracellular signal-regulated kinase 1 and 2 activations.

Conclusion: Propofol might attenuate H₂O₂-induced PC12 cell death through the inhibition of signaling pathways mediated by the p38 MAP kinase.

Keywords: propofol; oxidative stress; PC12 cells; apoptosis; p38 MAP kinase

¹This work was supported by a grant from the National Natural Science Foundation of China (No 30371731).

⁴Correspondence to Prof Yang LU and Prof Hong-zhuan CHEN.
Phn 86-21-6384-6590, ext 776466.
Fax 86-21-6467-4721.
E-mail huaxue@shsmu.edu.cn (Yang LU); yaoli@shsmu.edu.cn (Hong-zhuan CHEN)
Received 2006-12-24 Accepted 2007-02-13

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