title: Ursodeoxycholic acid suppresses mitochondria-dependent programmed cell death induced by sodium nitroprusside in SH-SY5Y cells.
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 (1mM)-induced cell death. Results showed that both UDCA and YS effectively attenuated the production of total reactive oxygen species (ROS), peroxynitrite (ONOO(-)) 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.
authors.affiliation: Department of Biotechnology, Chosun University, Gwangju 501-759, Republic of Korea. hsjeon@chosun.ac.kr
authors.forename: Hong Sung
authors.initials: HS
authors.lastname: Chun
authors.forename: Walter C
authors.initials: WC
authors.lastname: Low
mesh_terms: D016923:Cell Death / Q000187:drug effects*; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000378:metabolism*; D005978:Glutathione / Q000032:analysis / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009025:Morpholines / Q000494:pharmacology; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism; D009599:Nitroprusside / Q000378:metabolism* / Q000633:toxicity; D030421:Peroxynitrous Acid / Q000032:analysis / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
chemical_list: D002867:Chromones; D005978:Glutathione; D009025:Morpholines; D009569:Nitric Oxide; D009599:Nitroprusside; D030421:Peroxynitrous Acid; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species; D014580:Ursodeoxycholic Acid; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one