SirT1 Inhibition Reduces IGF-I/IRS-2/Ras/ERK1/2 Signaling and Protects Neurons

@article{citeulike:2953530, abstract = {Summary Sirtuins are known to protect cells and extend life span, but our previous studies indicated that S. cerevisiae Sir2 can also increase stress sensitivity and limit life-span extension. Here we provide evidence for a role of the mammalian Sir2 ortholog SirT1 in the sensitization of neurons to oxidative damage. SirT1 inhibition increased acetylation and decreased phosphorylation of IRS-2; it also reduced activation of the Ras/ERK1/2 pathway, suggesting that SirT1 may enhance IGF-I signaling in part by deacetylating IRS-2. Either the inhibition of SirT1 or of Ras/ERK1/2 was associated with resistance to oxidative damage. Markers of oxidized proteins and lipids were reduced in the brain of old SirT1-deficient mice, but the life span of the homozygote knockout mice was reduced under both normal and calorie-restricted conditions. These results are consistent with findings in S. cerevisiae and other model systems, suggesting that mammalian sirtuins can play both protective and proaging roles.}, author = {Li, Ying and Xu, Wei and Mcburney, Michael W. and Longo, Valter D. }, citeulike-article-id = {2953530}, doi = {http://dx.doi.org/10.1016/j.cmet.2008.05.004}, journal = {Cell Metabolism}, keywords = {igf1, sirt1, sirtuin}, month = {July}, number = {1}, pages = {38--48}, posted-at = {2008-07-02 21:39:51}, priority = {2}, title = {SirT1 Inhibition Reduces IGF-I/IRS-2/Ras/ERK1/2 Signaling and Protects Neurons}, url = {http://dx.doi.org/10.1016/j.cmet.2008.05.004}, volume = {8}, year = {2008} }

TY - JOUR ID - citeulike:2953530 L3 - citeulike-article-id:2953530 N2 - Summary Sirtuins are known to protect cells and extend life span, but our previous studies indicated that S. cerevisiae Sir2 can also increase stress sensitivity and limit life-span extension. Here we provide evidence for a role of the mammalian Sir2 ortholog SirT1 in the sensitization of neurons to oxidative damage. SirT1 inhibition increased acetylation and decreased phosphorylation of IRS-2; it also reduced activation of the Ras/ERK1/2 pathway, suggesting that SirT1 may enhance IGF-I signaling in part by deacetylating IRS-2. Either the inhibition of SirT1 or of Ras/ERK1/2 was associated with resistance to oxidative damage. Markers of oxidized proteins and lipids were reduced in the brain of old SirT1-deficient mice, but the life span of the homozygote knockout mice was reduced under both normal and calorie-restricted conditions. These results are consistent with findings in S. cerevisiae and other model systems, suggesting that mammalian sirtuins can play both protective and proaging roles. IS - 1 JF - Cell Metabolism EP - 48 TI - SirT1 Inhibition Reduces IGF-I/IRS-2/Ras/ERK1/2 Signaling and Protects Neurons VL - 8 SP - 38 KW - igf1 KW - sirt1 KW - sirtuin AU - Li, Ying AU - Xu, Wei AU - Mcburney, Michael AU - Longo, Valter PY - 2008/07/02/ UR - http://dx.doi.org/10.1016/j.cmet.2008.05.004 ER -