Cited 0 times in Scipus Cited Count

Glycogen Synthase Kinase 3 Inactivation Induces Cell Senescence through Sterol Regulatory Element Binding Protein 1-Mediated Lipogenesis in Chang Cells

Authors
Kim, YM | Song, I  | Seo, YH | Yoon, G
Citation
Endocrinology and metabolism (Seoul, Korea), 28(4). : 297-308, 2013
Journal Title
Endocrinology and metabolism (Seoul, Korea)
ISSN
2093-596X2093-5978
Abstract
Background: Enhanced lipogenesis plays a critical role in cell senescence via induction of expression of the mature form of sterol regulatory element binding protein 1 (SREBP1), which contributes to an increase in organellar mass, one of the indicators of senescence. We investigated the molecular mechanisms by which signaling molecules control SREBP1-mediated lipogenesis and senescence.



Methods: We developed cellular models for stress-induced senescence, by exposing Chang cells, which are immortalized human liver cells, to subcytotoxic concentrations (200 μM) of deferoxamine (DFO) and H2O2.



Results: In this model of stress-induced cell senescence using DFO and H2O2, the phosphorylation profile of glycogen synthase kinase 3α (GSK3α) and β corresponded closely to the expression profile of the mature form of SREBP-1 protein. Inhibition of GSK3 with a subcytotoxic concentration of the selective GSK3 inhibitor SB415286 significantly increased mature SREBP1 expression, as well as lipogenesis and organellar mass. In addition, GSK3 inhibition was sufficient to induce senescence in Chang cells. Suppression of GSK3 expression with siRNAs specific to GSK3α and β also increased mature SREBP1 expression and induced senescence. Finally, blocking lipogenesis with fatty acid synthase inhibitors (cerulenin and C75) and siRNA-mediated silencing of SREBP1 and ATP citrate lyase (ACL) significantly attenuated GSK3 inhibition-induced senescence.



Conclusion: GSK3 inactivation is an important upstream event that induces SREBP1-mediated lipogenesis and consequent cell senescence.
Keywords
DOI
10.3803/EnM.2013.28.4.297
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Medical Genetics
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
Ajou Authors
송, 인선  |  윤, 계순
Full Text Link
Files in This Item:
10.3803_EnM.2013.28.4.297.pdfDownload
Export

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse