| Inhibition of Endogenous Hydrogen Sulfide Generation is Associated with Homocysteine-Induced Neurotoxicity: Role of ERK1/2 Activation. | |
| | |
MedLine Citation:
|
PMID: 21104457 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
|
Both elevated homocysteine and decreased hydrogen sulfide (H(2)S) are observed in the brains of Alzheimer's disease (AD) patients. Reactive oxygen species (ROS) overproduction contributes to the neurotoxicity of homocysteine; however, H(2)S is an endogenous antioxidant gas. Therefore, the aim of this study was to investigate whether the imbalance of proportion to this endogenous protective antioxidant gas is involved in homocysteine-caused neurotoxicity. We show that homocysteine inhibits the generation of endogenous H(2)S and the expression and activity of cystathionine-β-synthetase (CBS), the main enzyme responsible for the generation of H(2)S in PC12 cells. S-Adenosylmethionine, an activator of CBS, not only prevents homocysteine-induced inhibition of endogenous H(2)S production but also attenuates homocysteine-triggered cytotoxicity and accumulation of ROS. We find that activation of ERK1/2 occurs in homocysteine-treated PC12 cells and blockade of ERK1/2 with U0126 abolished the homocysteine-induced cytotoxicity and inhibitory effect on endogenous H(2)S generation. These results indicate that homocysteine neurotoxicity involves reduction of H(2)S production, which is caused by inhibition of CBS and mediated by activation of ERK1/2. Our study suggests a promising future of H(2)S-based therapies for neurodegenerative diseases such as AD. |
| | |
Authors:
|
Xiao-Qing Tang; Xin-Tian Shen; Yi-E Huang; Rong-Qian Chen; Yan-Kai Ren; Heng-Rong Fang; Yuan-Yuan Zhuang; Chun-Yan Wang |
Related Documents
:
|
20680277 - Rapamycin suppresses ros-dependent apoptosis caused by selenomethionine in a549 lung ca... 12899937 - Pathways of cell signaling in hyperoxia. 20963497 - Acetylcholine prevents angiotensin ii-induced oxidative stress and apoptosis in h9c2 ce... 9815127 - Role of superoxide in apoptosis induced by growth factor withdrawal. 22003197 - The nlrp3 inflammasome contributes to brain injury in pneumococcal meningitis and is ac... 21765117 - Macrophage colony stimulating factor-induced macrophage differentiation influences myot... |
Publication Detail:
|
Type: Journal Article Date: 2010-11-23 |
Journal Detail:
|
Title: Journal of molecular neuroscience : MN Volume: 45 ISSN: 1559-1166 ISO Abbreviation: J. Mol. Neurosci. Publication Date: 2011 Sep |
Date Detail:
|
Created Date: 2011-07-27 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9002991 Medline TA: J Mol Neurosci Country: United States |
Other Details:
|
Languages: eng Pagination: 60-7 Citation Subset: IM |
Affiliation:
|
Department of Physiology, Medical College, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China, txq01001@gmail.com. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Increasing of Blood-tumor Barrier Permeability through Paracellular Pathway by Low-frequency Ultraso...
Next Document: Are cardiovascular benefits in statin lipid effects dependent on baseline lipid levels?