Document Detail


Protective effect of hydrogen sulphide against 6-OHDA-induced cell injury in SH-SY5Y cells involves PKC/PI3K/Akt pathway.
MedLine Citation:
PMID:  20735429     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: Hydrogen sulphide (H(2)S) is a novel neuromodulator. The present study aimed to investigate the protective effect of H(2)S against cell injury induced by 6-hydroxydopamine (6-OHDA), a selective dopaminergic neurotoxin often used to establish a model of Parkinson's disease for studying the underlying mechanisms of this condition.
EXPERIMENTAL APPROACH: Cell viability in SH-SY5Y cells was measured using MTT assay. Western blot analysis and pharmacological manipulation were employed to study the signalling mechanisms.
KEY RESULTS: Treatment of SH-SY5Y cells with 6-OHDA (50-200 microM) for 12 h decreased cell viability. Exogenous application of NaHS (an H(2)S donor, 100-1000 microM) or overexpression of cystathionine beta-synthase (a predominant enzyme to produce endogenous H(2)S in SH-SY5Y cells) protected cells against 6-OHDA-induced cell apoptosis and death. Furthermore, NaHS reversed 6-OHDA-induced loss of tyrosine hydroxylase. Western blot analysis showed that NaHS reversed the down-regulation of PKCalpha, epsilon and Akt and the up-regulation of PKCdelta in 6-OHDA-treated cells. Blockade of PKCalpha with Gö6976 (2 microM), PKCepsilon with EAVSLKPT (200 microM) or PI3K with LY294002 (20 microM) reduced the protective effects of H(2)S. However, inhibition of PKCdelta with rottlerin (5 microM) failed to affect 6-OHDA-induced cell injury. These data suggest that the protective effects of NaHS mainly resulted from activation of PKCalpha, epsilon and PI3K/Akt pathway. In addition, NaHS-induced Akt phosphorylation was significantly attenuated by Gö6976 and EAVSLKPT, suggesting that the activation of Akt by NaHS is PKCalpha, epsilon-dependent.
CONCLUSIONS AND IMPLICATIONS: H(2)S protects SH-SY5Y cells against 6-OHDA-induced cell injury by activating the PKCalpha, epsilon/PI3K/Akt pathway.
Authors:
Chi Xin Tiong; Ming Lu; Jin-Song Bian
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  161     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-25     Completed Date:  2011-01-04     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  467-80     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects
Blotting, Western
Cell Culture Techniques
Cell Line, Tumor
Cell Survival / drug effects
Cystathionine beta-Synthase / genetics
Humans
Hydrogen Sulfide / metabolism,  pharmacology*
Neuroprotective Agents / pharmacology*
Oxidopamine / toxicity*
Phosphatidylinositol 3-Kinases / metabolism*
Phosphorylation
Protein Kinase C / metabolism*
Proto-Oncogene Proteins c-akt / metabolism*
Transfection
Tyrosine 3-Monooxygenase / metabolism
Chemical
Reg. No./Substance:
0/Neuroprotective Agents; 1199-18-4/Oxidopamine; 7783-06-4/Hydrogen Sulfide; EC 1.14.16.2/Tyrosine 3-Monooxygenase; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.13/Protein Kinase C; EC 4.2.1.22/Cystathionine beta-Synthase
Comments/Corrections
Erratum In:
Br J Pharmacol. 2013 Apr;168(8):2011-2

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