Inhibition of cAMP-response element-binding protein activity decreases protein kinase B/Akt expression in 3T3-L1 adipocytes and induces apoptosis - PubMed (original) (raw)
. 2002 Jan 11;277(2):1426-32.
doi: 10.1074/jbc.M107923200. Epub 2001 Nov 1.
Affiliations
- PMID: 11694510
- DOI: 10.1074/jbc.M107923200
Free article
Inhibition of cAMP-response element-binding protein activity decreases protein kinase B/Akt expression in 3T3-L1 adipocytes and induces apoptosis
Jane E B Reusch et al. J Biol Chem. 2002.
Free article
Abstract
White adipose tissue mass is governed by competing processes that control lipid synthesis and storage, the development of new adipocytes, and their survival. We have shown that the transcription factor cAMP-response element-binding protein (CREB) participates in adipogenesis, with constitutively active forms of CREB inducing adipocyte differentiation and dominant negative forms of CREB blocking this process. In other cell types, CREB and related factors have been shown to play important roles in survival and apoptosis. Here we demonstrate that reduction of CREB activity by ectopic expression of the dominant negative CREB, KCREB, induces apoptosis of mature 3T3-L1 adipocytes in culture. Death by apoptosis was confirmed by increased nuclear condensation, changes in membrane morphology, and increased DNA fragmentation. Gene microarray analysis indicated that KCREB expression increased expression of several pro-apoptotic genes like Interleukin Converting Enzyme and decreased the expression of the anti-apoptotic signaling molecule, Akt/protein kinase B. Finally, introduction of constitutively active CREB, CREB-DIEDML, blocked death of mature adipocytes treated with TNF-alpha. The data indicate that CREB plays a central role in adipocyte survival, perhaps by regulating the expression of certain pro- and anti-apoptotic genes. These results not only extend the role of CREB in adipocyte biology but also highlight the general developmental and survival role of this factor in numerous cell and tissue types.
Similar articles
- CREB activation induces adipogenesis in 3T3-L1 cells.
Reusch JE, Colton LA, Klemm DJ. Reusch JE, et al. Mol Cell Biol. 2000 Feb;20(3):1008-20. doi: 10.1128/MCB.20.3.1008-1020.2000. Mol Cell Biol. 2000. PMID: 10629058 Free PMC article. - Depletion of cAMP-response element-binding protein/ATF1 inhibits adipogenic conversion of 3T3-L1 cells ectopically expressing CCAAT/enhancer-binding protein (C/EBP) alpha, C/EBP beta, or PPAR gamma 2.
Fox KE, Fankell DM, Erickson PF, Majka SM, Crossno JT Jr, Klemm DJ. Fox KE, et al. J Biol Chem. 2006 Dec 29;281(52):40341-53. doi: 10.1074/jbc.M605077200. Epub 2006 Oct 27. J Biol Chem. 2006. PMID: 17071615 - GIP increases human adipocyte LPL expression through CREB and TORC2-mediated trans-activation of the LPL gene.
Kim SJ, Nian C, McIntosh CH. Kim SJ, et al. J Lipid Res. 2010 Nov;51(11):3145-57. doi: 10.1194/jlr.M006841. Epub 2010 Aug 7. J Lipid Res. 2010. PMID: 20693566 Free PMC article. - Tumour necrosis factor-related apoptosis-inducing ligand sequentially activates pro-survival and pro-apoptotic pathways in SK-N-MC neuronal cells.
Milani D, Zauli G, Rimondi E, Celeghini C, Marmiroli S, Narducci P, Capitani S, Secchiero P. Milani D, et al. J Neurochem. 2003 Jul;86(1):126-35. doi: 10.1046/j.1471-4159.2003.01805.x. J Neurochem. 2003. PMID: 12807432 - cAMP/Protein Kinase A Signaling Inhibits Dlx5 Expression via Activation of CREB and Subsequent C/EBPβ Induction in 3T3-L1 Preadipocytes.
Lee HL, Qadir AS, Park HJ, Chung E, Lee YS, Woo KM, Ryoo HM, Kim HJ, Baek JH. Lee HL, et al. Int J Mol Sci. 2018 Oct 14;19(10):3161. doi: 10.3390/ijms19103161. Int J Mol Sci. 2018. PMID: 30322210 Free PMC article.
Cited by
- cAMP Response Element Binding Protein 1 (CREB1) Promotes Monounsaturated Fatty Acid Synthesis and Triacylglycerol Accumulation in Goat Mammary Epithelial Cells.
Yao D, Yang C, Ma J, Chen L, Luo J, Ma Y, Loor JJ. Yao D, et al. Animals (Basel). 2020 Oct 14;10(10):1871. doi: 10.3390/ani10101871. Animals (Basel). 2020. PMID: 33066354 Free PMC article. - Mitochondrial (dys)function in adipocyte (de)differentiation and systemic metabolic alterations.
De Pauw A, Tejerina S, Raes M, Keijer J, Arnould T. De Pauw A, et al. Am J Pathol. 2009 Sep;175(3):927-39. doi: 10.2353/ajpath.2009.081155. Epub 2009 Aug 21. Am J Pathol. 2009. PMID: 19700756 Free PMC article. Review. - Adipose tissue insulin sensitivity and macrophage recruitment: Does PI3K pick the pathway?
McCurdy CE, Klemm DJ. McCurdy CE, et al. Adipocyte. 2013 Jul 1;2(3):135-42. doi: 10.4161/adip.24645. Epub 2013 Apr 16. Adipocyte. 2013. PMID: 23991359 Free PMC article. - Hoxa5 increases mitochondrial apoptosis by inhibiting Akt/mTORC1/S6K1 pathway in mice white adipocytes.
Feng F, Ren Q, Wu S, Saeed M, Sun C. Feng F, et al. Oncotarget. 2017 Aug 24;8(56):95332-95345. doi: 10.18632/oncotarget.20521. eCollection 2017 Nov 10. Oncotarget. 2017. PMID: 29221131 Free PMC article. - Differential regulation of CIDEA and CIDEC expression by insulin via Akt1/2- and JNK2-dependent pathways in human adipocytes.
Ito M, Nagasawa M, Omae N, Ide T, Akasaka Y, Murakami K. Ito M, et al. J Lipid Res. 2011 Aug;52(8):1450-60. doi: 10.1194/jlr.M012427. Epub 2011 Jun 2. J Lipid Res. 2011. PMID: 21636835 Free PMC article.