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I.R.F. / Aging news / General / 09111601

SIRT1 And The Neuronal Survival Due To The Apoptotic Stimuli
Posted on: November 16, 2009

The mechanism involved in neuronal apoptosis is largely unknown. Studies performed on neuronal cell cultures provide information about the pathways which orchestrate the process of neuronal loss and potential drugs for the treatment of neurological disorders.

In the study resveratrol, a natural antioxidant, as a potential drug for the treatment of neurodegenerative diseases has been selected. By evaluating the neuroprotective effects of resveratrol in two apoptotic models in rat cerebellar granule neurons (CGNs): the inhibition of mitochondrial complex I using 1-methyl-4-phenylpyridinium (MPP(+)) (an in vitro model of Parkinson's disease) and serum potassium withdrawal.

The role of the mammalian silent information regulator 2 (SIRT1) in the process of neuroprotection mediated by resveratrol has been studied.

Because recent studies have demonstrated that SIRT1 is involved in cell survival and has antiaging properties, changes in the expression of this protein after the addition of these two apoptotic stimuli were also measured. MPP(+)--induced loss of cell viability and apoptosis in CGNs was prevented by the addition of RESV (1 microM to 100 microM). However, the neuroprotective effects were not mediated by the activation of SIRT1, since sirtinol - an inhibitor of this enzyme - did not attenuate them. Furthermore MPP(+) decreases the protein expression of SIRT1. RESV did not prevent serum potassium withdrawal - induced apoptosis although it did completely attenuate oxidative stress production by these apoptotic stimuli. Furthermore, serum potassium withdrawal increases the expression of SIRT1.

Results indicate that the antiapoptotic effects of RESV in MPP(+) are independent of the stimulation of SIRT1 and depend on its antioxidant properties. Furthermore, because SIRT1 is involved in neuronal survival depending on the apoptotic stimuli, changes in the expression of SIRT1 could be involved in the regulation of the apoptotic route.

Source: Alvira D, Yeste-Velasco M, Folch J, Verdaguer E, Canudas AM, Pallas M, Camins A. Comparative analysis of the effects of resveratrol in two apoptotic models: inhibition of complex I and potassium deprivation in cerebellar neurons.; Neuroscience. 2007 Jul 13;147(3):746-56. Epub 2007 Jun 20.
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