| 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 |
Related Documents
:
|
21169429 - Autophagy deficiency promotes {beta}-lactam production in penicillium chrysogenum. 15637049 - Pkc1 and the upstream elements of the cell integrity pathway in saccharomyces cerevisia... 12714179 - Human adenoma cells are highly susceptible to the genotoxic action of 4-hydroxy-2-nonenal. 11694029 - Protective effects of debo on zinc-induced apoptosis of c6 glial cells via modulation o... 1897959 - Paraquat-resistant hela cells: increased cellular content of glutathione peroxidase. 9101039 - Vitamin e protection of cell morphology under oxidative stress is related to cytoskelet... 12923319 - Distinct patterns of cleavage and translocation of cell cycle control proteins in cd95-... 12028819 - Micronuclei induced by sulfur dioxide inhalation in mouse bone-marrow cells in vivo. 10875939 - Rapsynoid/partner of inscuteable controls asymmetric division of larval neuroblasts in ... |
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: 2013-05-06 |
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. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Histamine H1 receptor antagonist cetirizine impairs working memory processing speed, but not episodi...
Next Document: Identification of endothelial cell-specific molecule-1 as a potential serum marker for colorectal ca...