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Roles of GSK3 in metabolic shift toward abnormal anabolism in cell senescence.

Authors
Kim, YM; Seo, YH; Park, CB; Yoon, SH; Yoon, G
Citation
Annals of the New York Academy of Sciences, 120165-71, 2010
Journal Title
Annals of the New York Academy of Sciences
ISSN
0077-89231749-6632
Abstract
Diverse metabolic alterations, including mitochondrial dysfunction, have often been reported as characteristic phenotypes of senescent cells. However, the overall consequence of senescent metabolic features, how they develop, and how they are linked to other senescent phenotypes, such as enlarged cell volume, increased granularity, and oxidative stress, is not clear. We investigated the potential roles of glycogen synthase kinase 3 (GSK3), a multifunctional kinase, in the development of the metabolic phenotypes in cell senescence. The inactivation of GSK3 via phosphorylation is commonly observed in diverse cell senescences. Furthermore, subcytotoxic concentration of GSK3 inhibitor was sufficient to induce cellular senescence, accompanied by augmented anabolism, such as enhanced protein synthesis, and increased glycogenesis and lipogenesis, in addition to mitochondrial dysfunction. Anabolism was accomplished through glycogen synthase, eIF2B, and SREBP1. These metabolic features seem to contribute to an increase in cellular mass by increasing glycogen granules, protein mass, and organelles. Taken together, our results suggest that GSK3 is one of the key modulators of metabolic alteration, leading the cells to senescence.
MeSH terms
AnimalsCell Aging/physiology*Cell LineFluorescent Dyes/pharmacologyGlycogen Synthase Kinase 3/metabolismGlycogen Synthase Kinase 3/physiology*HumansMitochondria/metabolismModels, BiologicalOxidative StressOxygen ConsumptionPhenotypePhosphorylationReactive Oxygen SpeciesSterol Regulatory Element Binding Protein 1/metabolism
DOI
10.1111/j.1749-6632.2010.05617.x
PMID
20649541
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
Journal Papers > School of Medicine / Graduate School of Medicine > Neurosurgery
AJOU Authors
박찬배윤수한윤계순
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