Ghrelin prevents 1-methyl-4-phenylpyridinium ion-induced cytotoxicity through antioxidation and NF-kappaB modulation in MES23.5 cells.
Ghrelin, a 28-amino acid peptide, is an endogenous ligand for the growth hormone secretagogue (GHS) receptor. Our previous data showed that ghrelin could inhibit apoptosis in Parkinson's disease (PD) models both in vitro and in vivo. There is now growing evidence that oxidative stress has a critical role in the etiology of PD. And ghrelin was reported to possess anti-inflammatory, antioxidant effects. Dose ghrelin protect dopaminergic neurons by its antioxidant effect? In the present study, 1-methyl-4-phenylpyridinium (MPP(+)) was used to evaluate the possible antioxidant effects of ghrelin on MPP(+)-induced neurotoxicity in MES23.5 cells and the underlying mechanisms. Our results showed that MPP(+) significantly increased malonaldehyde (MDA) level and Bax/Bcl2 ratio, reduced the level of Cu-Zn superoxide dismutase (SOD) and catalase (CAT). Ghrelin protected MES23.5 cells against MPP(+)-induced neurotoxicity by reversing these changes. Furthermore, ghrelin pretreatment significantly inhibited MPP(+)-induced nuclear factor-kappaB translocation. These results suggest that the protective effects of ghrelin on MPP(+)-induced cytotoxicity may be ascribed to its antioxidative properties, and the modulation of nuclear factor-kappaB.
Liu
Li
L
Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, Qingdao, 266071, China.
Xu
Huamin
H
Jiang
Hong
H
Wang
Jun
J
Song
Ning
N
Xie
Junxia
J
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002461:Cell Line, Transformed; D019938:Cyclin D1 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D054439:Ghrelin / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D008636:Mesencephalon / Q000166:cytology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000975:Antioxidants; D054439:Ghrelin; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D019938:Cyclin D1; D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D015655:1-Methyl-4-phenylpyridinium