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A novel mTOR activating protein protects dopamine neurons against oxidative stress by repressing autophagy related cell death
- A novel mTOR activating protein protects dopamine neurons against oxidative stress by repressing autophagy related cell death
- Choi K.-C.; Kim S.-H.; Ha J.-Y.; Kim S.-T.; Son J.H.
- Ewha Authors
- 김상태; 손형진
- SCOPUS Author ID
- Issue Date
- Journal Title
- Journal of Neurochemistry
- Journal of Neurochemistry vol. 112, no. 2, pp. 366 - 376
- SCI; SCIE; SCOPUS
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- Our previous microarray analysis identified a neuroprotective protein Oxi-α, that was down-regulated during oxidative stress (OS)-induced cell death in dopamine neurons [Neurochem. Res. (2004) vol. 29, pp. 1223]. Here we find that the phylogenetically conserved Oxi-α protects against OS by a novel mechanism: Activation of the mammalian target of rapamycin (mTOR) kinase and subsequent repression of autophagic vacuole accumulation and cell death. To the best of our knowledge, Oxi-α is the first molecule discovered in dopamine neurons, which activates mTOR kinase. Indeed, the down-regulation of Oxi-α by OS suppresses the activation of mTOR kinase. The pathogenic effect of down-regulated Oxi-α was confirmed by gene-specific knockdown experiment, which resulted in not only the repression of mTOR kinase and the subsequent phosphorylation of p70 S6 kinase and 4E-BP1, but also enhanced susceptibility to OS. In accordance with these observations, treatment with rapamycin, an mTOR inhibitor and autophagy inducer, potentiated OS-induced cell death, while similar treatment with an autophagy inhibitor, 3-methyladenine protected the dopamine cells. Our findings present evidence for the presence of a novel class of molecule involved in autophagic cell death triggered by OS in dopamine neurons. © 2009 International Society for Neurochemistry.
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