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一种新型小鼠过氧化物酶体增殖物激活受体α调控且饥饿诱导的基因Ppsig的鉴定与表征

Identification and characterization of a novel mouse peroxisome proliferator-activated receptor alpha-regulated and starvation-induced gene, Ppsig.

作者信息

Sun Yan, Ng Lui, Lam Wun, Lo Cherry Kam-Chun, Chan Pui-Ting, Yuen Yee-Lok, Wong Pui-Fong, Tsang David Sau-Cheuk, Cheung Wing-Tai, Lee Susanna Sau-Tuen

机构信息

Department of Biochemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.

出版信息

Int J Biochem Cell Biol. 2008;40(9):1775-91. doi: 10.1016/j.biocel.2008.01.006. Epub 2008 Jan 16.

Abstract

The peroxisome proliferator-activated receptor alpha (PPARalpha) has been known to play a pivotal role in maintaining the energy balance during fasting; however, the battery of PPARalpha target genes involved in this metabolic response is still not fully characterized. Here, we report the identification and characterization of Ppsig (for PPARalpha-regulated and starvation-induced gene) with unknown biological function from mouse liver. Multiple Ppsig cDNAs which differed in the 3'-untranslated regions were identified. The open reading frame of Ppsig cDNA is 1830 bp which encodes a protein of 67.33 kDa. Ppsig contains 11 exons spanning at least 10 kb. Although the exact biological function of Ppsig is still not known, we found that Ppsig mRNA transcript was dramatically up-regulated during 72 h fasting and following treatment with a potent PPARalpha agonist, in a tissue-specific and PPARalpha-dependent manner. A functional peroxisome proliferator-response element was found in the intron 1 of Ppsig, thus confirming that Ppsig is a novel direct mouse PPARalpha target gene. This finding might help in elucidating the transcriptional regulatory mechanism of Ppsig in the cellular response to fasting.

摘要

过氧化物酶体增殖物激活受体α(PPARα)在禁食期间维持能量平衡中发挥关键作用,然而,参与这种代谢反应的一系列PPARα靶基因仍未完全明确。在此,我们报告从小鼠肝脏中鉴定并表征了具有未知生物学功能的Ppsig(PPARα调节和饥饿诱导基因)。鉴定出多个3'非翻译区不同的Ppsig cDNA。Ppsig cDNA的开放阅读框为1830 bp,编码一个67.33 kDa的蛋白质。Ppsig包含11个外显子,跨度至少为10 kb。尽管Ppsig的确切生物学功能尚不清楚,但我们发现Ppsig mRNA转录本在禁食72小时期间以及用强效PPARα激动剂处理后以组织特异性和PPARα依赖性方式显著上调。在Ppsig的内含子1中发现了一个功能性过氧化物酶体增殖物反应元件,从而证实Ppsig是一个新的直接小鼠PPARα靶基因。这一发现可能有助于阐明Ppsig在细胞对禁食反应中的转录调控机制。

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