RRC ID 37776
著者 Shimizu YI, Morita M, Ohmi A, Aoyagi S, Ebihara H, Tonaki D, Horino Y, Iijima M, Hirose H, Takahashi S, Takahashi Y.
タイトル Fasting induced up-regulation of activating transcription factor 5 in mouse liver.
ジャーナル Life Sci
Abstract AIMS:Food deprivation (fasting) is commonly encountered in the lives of animals and humans. In mammals, adaptive responses predominantly include the induction of hepatic gluconeogenesis, but the regulatory mechanisms remain unclear. Atf5 (activating transcription factor 5) is a transcription factor of the ATF/cAMP response element-binding protein family and is expressed abundantly in human liver. Atf5 has been associated with stress responses, cell differentiation, proliferation, and survival. However, its role in the liver response to in vivo food deprivation has not yet been investigated.
MAIN METHODS:Adult mice were food-deprived for 48 h and the expression of two Atf5 mRNA subtypes (Atf5-R1 and Atf-R2) and gluconeogenic factors was investigated. Using in vitro cell culture, Pgc-1alpha (peroxisome proliferator-activated receptor-gamma coactivator-1alpha) promoter activities after ectopic expression of Atf5 and Cebpg (CCAAT/enhancer-binding protein gamma) proteins were measured.
KEY FINDINGS:The Atf5-R1 transcript was found to be abundant in liver and other energy metabolism-related organs; Atf5-R2 was prominent in the testis. Fasting resulted in elevation of the expression of both Atf5-R1 and R2 in the liver. Interestingly, up-regulation of Atf5 was accompanied by increased expression of Cebpg and Pgc-1alpha. In human hepatoma cells (HepG2), but not in human cervical carcinoma cells (HeLa), forced expression of Atf5 and Cebpg cooperatively stimulated Pgc-1alpha promoter activity, suggesting that hepatic Pgc-1alpha could be induced by Atf5 and Cebpg in cooperation with other hepatic factors.
SIGNIFICANCE:Hepatic Atf5 might be potentially involved in the induction of gluconeogenetic factors during in vivo fasting stress.
巻・号 84(25-26)
ページ 894-902
公開日 2009-6-19
DOI 10.1016/j.lfs.2009.04.002
PII S0024-3205(09)00160-X
PMID 19376136
MeSH Activating Transcription Factors / genetics* Activating Transcription Factors / metabolism Animals Base Sequence CCAAT-Enhancer-Binding Proteins / genetics CCAAT-Enhancer-Binding Proteins / metabolism Cell Line, Tumor Embryo, Mammalian / embryology Embryo, Mammalian / metabolism* Fasting* Female Humans Liver / metabolism* Liver / ultrastructure Male Mice Mice, Inbred C57BL Pregnancy Promoter Regions, Genetic RNA, Messenger / analysis RNA, Messenger / genetics Transcription Factors / genetics Transcription Factors / metabolism Transfection Up-Regulation
IF 3.647
引用数 12
WOS 分野 MEDICINE, RESEARCH & EXPERIMENTAL PHARMACOLOGY & PHARMACY
リソース情報
ヒト・動物細胞 HeLaS3 Hep G2