Abstract |
We have isolated a gene, the c subunit (ATP6L) of vacuolar H(+)-ATPase, involved in oxidative stress response. In this study, we examined the role of ATP6L and its molecular mechanisms in glial cell death induced by H(2)O(2). Expression of the ATP6L gene was increased by H(2)O(2) treatment in C6 glial cells. ATP6L siRNA-transfected C6 cells treated with H(2)O(2) showed a significant decrease in viability. ATP6L siRNA-transfected cells that were pretreated with MEK1/2 inhibitor completely recovered cell viability. Pretreatment of the transfected cells with zVAD-fmk, a pan-specific caspase inhibitor, did not result in the recovery of cell viability, as determined by a H(2)O(2)-induced cytotoxicity assay. The ultrastructural morphology of the transfected cells as seen by the use of transmission electron microscopy showed numerous cytoplasmic autophagic vacuoles with double membrane. These results suggest that ATP6L has a protective role against H(2)O(2)-induced cytotoxicity via an inhibition of the Erk1/2 signaling pathway, leading to inhibition of autophagic cell death.
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Authors | Yu Jeong Byun, Seong-Beom Lee, Dong Jin Kim, Hwa Ok Lee, Min Jeong Son, Chul Woo Yang, Ki-Wug Sung, Ho-Shik Kim, Oh-Joo Kwon, In-Kyung Kim, Seong-Whan Jeong |
Journal | Neuroscience letters
(Neurosci Lett)
Vol. 425
Issue 3
Pg. 183-7
(Oct 02 2007)
ISSN: 0304-3940 [Print] Ireland |
PMID | 17845832
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Enzyme Inhibitors
- Oxidants
- Protein Subunits
- RNA, Small Interfering
- Hydrogen Peroxide
- Extracellular Signal-Regulated MAP Kinases
- MAP Kinase Kinase 1
- Vacuolar Proton-Translocating ATPases
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Topics |
- Animals
- Autophagy
(drug effects, physiology)
- Brain
(enzymology, physiopathology)
- Cell Death
(drug effects, physiology)
- Cell Line, Tumor
- Cell Survival
(drug effects, physiology)
- Cytoprotection
(drug effects, physiology)
- Enzyme Inhibitors
(pharmacology)
- Extracellular Signal-Regulated MAP Kinases
(antagonists & inhibitors, metabolism)
- Glioma
- Hydrogen Peroxide
(toxicity)
- MAP Kinase Kinase 1
(antagonists & inhibitors, metabolism)
- Microscopy, Electron, Transmission
- Neuroglia
(drug effects, enzymology)
- Oxidants
(toxicity)
- Oxidative Stress
(drug effects, physiology)
- Protein Subunits
(genetics, metabolism)
- RNA, Small Interfering
- Rats
- Transfection
- Vacuolar Proton-Translocating ATPases
(genetics, metabolism)
- Vacuoles
(enzymology, ultrastructure)
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