|本期目录/Table of Contents|

[1]邹 磊,王玉华,蔡春友,等.PCAF通过调控FOXO1活性参与3T3-L1前脂肪细胞分化[J].天津医科大学学报,2015,21(03):203-207.
 ZOU Lei,WANG Yu-hua,CAI Chun-you,et al.P300/CBP associated factor regulates adipogenesis of 3T3-L1 cells by controlling FOXO1[J].Journal of Tianjin Medical University,2015,21(03):203-207.
点击复制

PCAF通过调控FOXO1活性参与3T3-L1前脂肪细胞分化(PDF)
分享到:

《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
21卷
期数:
2015年03期
页码:
203-207
栏目:
基础医学
出版日期:
2015-05-20

文章信息/Info

Title:
P300/CBP associated factor  regulates adipogenesis of 3T3-L1 cells by controlling FOXO1
文章编号:
1006-8147(2015)03-0203-05
作者:
邹 磊王玉华蔡春友魏凤江杨付花焦红肖凌 超时文涛李卫东
(天津医科大学基础医学研究中心,天津300070)
Author(s):

 ZOU Lei WANG Yu-hua CAI Chun-you WEI Feng-jiang YANG Fu-hua JIAO Hong-xiao LING Chao SHI Wen-tao LI Wei-dong

 (Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China)
关键词:
PCAF3T3-L1细胞FOXO1转录调控
Keywords:
P300/CBP associated factor 3T3-L1 cell line FOXO1 transcriptional control
分类号:
Q254
DOI:
-
文献标志码:
A
摘要:
目的:在3T3-L1细胞模型中,探讨组蛋白乙酰转移酶PCAF对脂肪细胞分化调控的分子机制。方法:应用Real-time PCR和Western blot检测PCAF在3T3-L1细胞分化过程中的表达;应用重组慢病毒感染细胞,shRNA干扰或过表达PCAF,通过Oil-Red-O染色法观察PCAF表达量变化对细胞分化的影响;应用ChIP on chip和PCR array的方法筛选PCAF调控的下游基因和通路;应用Western blot和ChIP qPCR对潜在目的基因进行验证。结果:PCAF在3T3-L1细胞分化过程中表达升高;PCAF表达下调会抑制脂肪细胞的分化;PCAF可以在细胞分化不同时间点诱导PDPK1和FOXO1的表达,并间接影响了FOXO1磷酸化。结论:组蛋白乙酰转移酶PCAF通过胰岛素通路(PI3K/PDPK1/AKT/FOXO1)参与对脂肪细胞分化的转录调控。
Abstract:
Objective: To investigate the molecular mechanism of PCAF gene in regulation of adipocytes differentiation. Methods: PCAF expression levels were measured by Real-time PCR and Western blot in 3T3-L1 cells during differentiation; 3T3-L1 cells were transfected by recombinant Lentiviral ORF/shRNA and the effects of PCAF overexpression or knockdown on differentiation were observed by Oil-Red-O staining; ChIP on chip and PCR array were used to screen the signaling pathways regulated by PCAF; Expressions of potential target genes and pathways were detected by Western blot and ChIP qPCR. Results: PCAF expression increased during 3T3-L1 cells differentiation and adipogenesis; the differentiation of 3T3-L1 might be interfered by knockdown of PCAF ; Expression of PDPK1 and FOXO1 were induced by PCAF at various time points during 3T3-L1 differentiation; the phosphorylation of FOXO1 was also regulated by PCAF indirectly. Conclusion: PCAF regulates preadipocytes differentiation through the insulin pathway (PI3K/PDPK1/AKT /FOXO1).

参考文献/References:

[1]Rosen E D, Spiegelman B M. Adipocytes as regulators of energy balance and glucose homeostasis[J]. Nature, 2006, 444(7121): 847
[2]Ju D P, Zhan L X. Developments in regulation of adipocytes differentiation[J]. Chin J Cell Biol,, 2010, 32(5): 690
[3]Farmer S R. Transcriptional control of adipocyte formation[J]. Cell Metab, 2006, 4(4): 263
[4]Nakae J, Kitamura T, Kitamura Y, et al. The forkhead transcription factor Foxo1 regulates adipocyte differentiation[J]. Dev Cell, 2003, 4(1): 119
[5]Davis K E, Moldes M, Farmer S R. The forkhead transcription factor FoxC2 inhibits white adipocyte differentiation[J]. J Biol Chem, 2004, 279(41): 42453
[6]Ravnskjaer K, Hogan M F, Lackey D, et al. Glucagon regulates gluconeogenesis through KAT2B- and WDR5-mediated epigenetic effects[J]. J Clin Invest, 2013, 123(10): 4318
[7]Wiper-Bergeron N, Salem H A, Tomlinson J J, et al. Glucocorticoid-stimulated preadipocyte differentiation is mediated through acetylation of C/EBPbeta by GCN5[J]. Proc Natl Acad Sci U S A, 2007, 104(8): 2703
[8]Gupta P, Park S W, Farooqui M, et al. Orphan nuclear receptor TR2, a mediator of preadipocyte proliferation, is differentially regulated by RA through exchange of coactivator PCAF with corepressor RIP140 on a platform molecule GRIP1[J]. Nucleic Acids Res, 2007, 35(7): 2269
[9]Park S W, Huang W H, Persaud S D, et al. RIP140 in thyroid hormone-repression and chromatin remodeling of Crabp1 gene during adipocyte differentiation[J]. Nucleic Acids Res, 2009, 37(21): 7085
[10]Zhou Y F, Peng J, Jiang S W. Role of histone acetyltransferases and histone deacetylases in adipocyte differentiation and adipogenesis[J]. Eur J Cell Biol, 2014, 93(4): 170
[11]Nakae J, Kitamura T, Ogawa W, et al. Insulin regulation of gene expression through the forkhead transcription factor Foxo1 (Fkhr) requires kinases distinct from Akt[J]. Biochemistry, 2001, 40(39): 11768
[12]Nakae J, Biggs W H, Kitamura T, et al. Regulation of insulin action and pancreatic beta-cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1[J]. Nat Genet, 2002, 32(2): 245
[13]Nakae J, Barr V, Accili D. Differential regulation of gene expression by insulin and IGF-1 receptors correlates with phosphorylation of a single amino acid residue in the forkhead transcription factor FKHR[J]. EMBO J, 2000, 19(5): 989
[14]金生浩,廖侃.脂肪细胞分化的转录调控[J].生命的化学,1999,19(5):216

相似文献/References:

备注/Memo

备注/Memo:
基金项目 国家自然科学基金资助项目(31201029,81070576);教育部博士点基金资助项目(20111202120002);天津市应用基础及前沿技术研究计划(12JCZDJC24700)
作者简介 邹磊(1984-),男,硕士在读,研究方向:病理与病理生理学;

通信作者:时文涛,shiwentao@tijmu.edu.cn;李卫东,liweidong98@tijmu.edu.cn

更新日期/Last Update: 2015-05-27