Hydrogen sulfide inhibits MPP(+)-induced apoptosis in PC12 cells.
OBJECTIVE
Hydrogen sulfide (H2S) is a well-known cytotoxic gas. Recently it has been shown to protect neurons against oxidative stress caused by glutamate, hypochlorous acid (HOCl), and beta-amyloid. The aim of the present study is to explore the cytoprotection of H2S against 1-methyl-4-phenylpyridinium ion (MPP(+))-induced apoptosis and the molecular mechanisms underlying in PC12 cells, a rat cell line derived from pheochromocytoma cells.


METHODS
Cell viability was determined by the conventional 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay. Apoptosis was assessed by Hoechst 33258 nuclear staining and flow cytometric (FCM) analysis after propidium iodide staining. The mitochondrial membrane potential (MMP) was measured by rhodamine 123 (Rh123) probe and reactive oxygen species (ROS) were measured by dihydrorhodamine probe using FCM analysis.


RESULTS
MPP(+) reduced the cell viability and induced apoptosis of PC12 cells along with dissipation of MMP as well as overproduction of ROS. Sodium hydrosulfide (NaHS), a H2S donor, protected PC12 cells against MPP(+)-induced cytotoxicity and apoptosis not only by reducing the loss of MMP, but also by attenuating an increase in intracellular ROS.


CONCLUSIONS
H2S significantly protected PC12 cells against cytotoxicity and apoptosis induced by MPP(+), which was associated with the inhibition by H(2)S of MPP(+)-induced dissipation of MMP and overproduction of ROS. These findings can significantly advance therapeutic approaches to the neurodegenerative diseases which are associated with oxidative stress, such as Parkinson's disease.
Yin
Wei-Lan
WL
Department of Physiology, Medical College, University of South China, 28 West Changsheng Road, Hengyang, 421001, Hunan, PR China.
He
Jian-Qin
JQ
Hu
Bi
B
Jiang
Zhi-Sheng
ZS
Tang
Xiao-Qing
XQ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection; D005434:Flow Cytometry; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013778:Tetrazolium Salts / Q000633:toxicity*; D013844:Thiazoles / Q000633:toxicity*
D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D020782:Matrix Metalloproteinases; C022616:thiazolyl blue; D006862:Hydrogen Sulfide