TAILIEUCHUNG - Báo cáo khoa học: Glutamine stimulates the gene expression and processing of sterol regulatory element binding proteins, thereby increasing the expression of their target genes

Here we show that the larger the amount of glutamine added to the med-ium, the more the expression of genes related to lipid homeostasis is pro-moted by the activation of sterol regulatory element binding proteins (SREBPs) at the transcriptional and post-translational levels in human hep-atoma HepG2 cells. | IFEBS Journal Glutamine stimulates the gene expression and processing of sterol regulatory element binding proteins thereby increasing the expression of their target genes Jun Inoue Yuka Ito Satoko Shimada Shin-ich Satoh Takashi Sasaki Tsutomu Hashidume Yuki Kamoshida Makoto Shimizu and Ryuichiro Sato Department of Applied BiologicalChemistry Graduate Schoolof Agriculturaland Life Sciences University of Tokyo Japan Keywords glutamine processing Sp1 SREBP transcriptional regulation Correspondence R. Sato 1-1-1 Yayoi Bunkyo-ku Tokyo 113-8657 Japan Fax 81 5841 8029 Tel 81 5841 5136 E-mail aroysato@ Received 17 March 2011 revised 23 May 2011 accepted 1 June 2011 doi Here we show that the larger the amount of glutamine added to the medium the more the expression of genes related to lipid homeostasis is promoted by the activation of sterol regulatory element binding proteins SREBPs at the transcriptional and post-translational levels in human hepatoma HepG2 cells. Glutamine increases the mRNA levels of several SREBP targets including SREBP-2. The gene expression of SREBP-1a a predominant form of SREBP-1 in most cultured cells and a target of the general transcription factor Sp1 is significantly augmented by glutamine via an increased binding of Sp1 to the SREBP-1a promoter. In contrast the increased expression of SREBP targets including SREBP-2 is due to stimulation of the processing of SREBP proteins by glutamine. It is also shown that glutamine accelerates SREBP processing through increased transport of the SREBP SREBP cleavage-activating protein complex from the endoplasmic reticulum to the Golgi apparatus. The processing of activating transcription factor 6 is activated by the same proteases as SREBPs in the Golgi in response to endoplasmic reticulum stress and is not induced by glutamine. Taken together these results clearly demonstrate that glutamine brings about not only the induction of SREBP-1a transcription

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