Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5859632 | Toxicology | 2012 | 8 Pages |
Abstract
Although ursodeoxycholic acid (UDCA) and its highly water-soluble formula (Yoo's solution; YS) have been shown to prevent neuronal damage, the effects of UDCA or YS against Parkinson's disease (PD)-related dopaminergic cell death has not been studied. This study investigated the protective effects of UDCA and YS on sodium nitroprusside (SNP)-induced cytotoxicity in human dopaminergic SH-SY5Y cells. Both UDCA (50-200 μM) and YS (100-200 μM) dose-dependently prevented SNP (1 mM)-induced cell death. Results showed that both UDCA and YS effectively attenuated the production of total reactive oxygen species (ROS), peroxynitrite (ONOOâ) and nitric oxide (NO), and markedly inhibited the mitochondrial membrane potential (MMP) loss and intracellular reduced glutathione (GSH) depletion. SNP-induced programmed cell death events, such as nuclear fragmentation, caspase-3/7 and -9 activation, Bcl-2/Bax ratio decrease, and cytochrome c release, were significantly attenuated by both UDCA and YS. Furthermore, selective inhibitor of phosphatidylinositiol-3-kinase (PI3K), LY294002, and Akt/PKB inhibitor, triciribine, reversed the preventive effects of UDCA on the SNP-induced cytotoxicity and Bax translocation. These results suggest that UDCA can protect SH-SY5Y cells under programmed cell death process by regulating PI3K-Akt/PKB pathways.
Keywords
PKCGö6983TriciribineDopaminergic cellDHR123UDCALY294002TUDCAPKBpKaPI3KRNSMMP2′,7′-dichlorodihydrofluorescein diacetateH2DCFDAROSTauroursodeoxycholic acidUrsodeoxycholic acidParkinson's diseaseApoptosisdihydrorhodaminephosphatidylinositol-3-kinasesodium nitroprussideNitric oxideMitochondrial membrane potentialprotein kinase Aprotein kinase BProtein kinase CPropidium iodideSNPreactive nitrogen species
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Authors
Hong Sung Chun, Walter C. Low,