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Mammalian Sir2-related protein (SIRT) 2–mediated modulation of resistance to axonal degeneration in slow Wallerian degeneration mice: A crucial role of tubulin deacetylation
- Source :
-
Neuroscience . Jul2007, Vol. 147 Issue 3, p599-612. 14p. - Publication Year :
- 2007
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Abstract
- Abstract: It has been shown that Wallerian degeneration, an anterograde degeneration of transected axons, is markedly delayed in a mutant mouse called slow Wallerian degeneration (Wld S ). These mice also show resistance to axonal degeneration caused by microtubule depolymerizing drugs, suggesting that axonal microtubules are stabilized. Here, we have focused on tubulin acetylation, a post-translational modification associated with microtubule stability. We found that the basal level of microtubule acetylation was increased in cultured cerebellar granule cells from Wld S mice. Nicotinamide but not 3-aminobenzamide, an inhibitor for poly(ADP)ribose polymerase, enhanced tubulin acetylation and resistance to axonal degeneration in cultured cerebellar granule cells from wild-type (WT) mice, suggesting that mammalian Sir2-related protein (SIRT) 2, a nicotinamide adenine dinucleotide (NAD)–dependent tubulin deacetylase, could modulate resistance to axonal degeneration. Indeed, the levels of NAD and SIRT2 were decreased in the cytoplasm from Wld S granule cells. Moreover, SIRT2 overexpression abrogated microtubule hyperacetylation and resistance to axonal degeneration in these cells. Conversely, SIRT2 knockdown by using a lentiviral vector expressing small interfering RNA, enhanced microtubule acetylation and resistance to axonal degeneration in WT granule cells. Taken together, these results suggest that SIRT2-mediated tubulin deacetylation is involved in both microtubule hyperacetylation and resistance to axonal degeneration in Wld S granule cells. [Copyright &y& Elsevier]
- Subjects :
- *EUGENICS
*GREEN fluorescent protein
*NIACIN
*CARBOXYLIC acids
Subjects
Details
- Language :
- English
- ISSN :
- 03064522
- Volume :
- 147
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 25569465
- Full Text :
- https://doi.org/10.1016/j.neuroscience.2007.04.059