MIT的科學(xué)家最近發(fā)現(xiàn)一種被認(rèn)為能延長(zhǎng)壽命的基因和清除體內(nèi)的膽固醇過(guò)程有關(guān),。這一發(fā)現(xiàn)能幫助科學(xué)家設(shè)計(jì)降低高膽固醇導(dǎo)致的各種疾病風(fēng)險(xiǎn)的藥物,，包括動(dòng)脈硬化癥和阿茲海默癥等,。
科學(xué)家研究了這種被稱為SIRT1的基因,，它通過(guò)激活一種細(xì)胞路徑,，并由HDL（高密度脂蛋白或“好膽固醇”）將體內(nèi)膽固醇清除,，最終阻止膽固醇形成,。MIT的生物學(xué)教授Leonard Guarente是文章主要作者,，他說(shuō)：“SIRT1是調(diào)節(jié)膽固醇的重要基因,，因此它在和膽固醇相關(guān)的多種老年疾病中起著作用。”研究結(jié)果發(fā)表在10月12日的《分子細(xì)胞》（Molecular Cell）上,。
提高SIRT1作用的藥物能降低膽固醇疾病的風(fēng)險(xiǎn),，例如多酚類藥物，這是紅酒中發(fā)現(xiàn)的能增強(qiáng)SIRT1作用的物質(zhì),。但是紅酒中自然存在的含量不足以對(duì)膽固醇濃度造成顯著影響,。
在較早的研究中，Guarente發(fā)現(xiàn)能通過(guò)極端限制能量來(lái)實(shí)現(xiàn)高濃度的SIRT1,，但這并不適合大部分人,。Guarente說(shuō)：“一旦有能增強(qiáng)SIRT1表達(dá)的藥物，就能得到類似能量限制的效果。這將提高人們的健康水平,。”
SIRT1是哺乳動(dòng)物中類似SIR2的基因,，SIR2被發(fā)現(xiàn)能延緩酵母和蛔蟲(chóng)的衰老?？茖W(xué)家想知道SIRT1是否有相同的效果,。在MIT進(jìn)行的新研究中，科學(xué)家發(fā)現(xiàn)較低的SIRT1將通過(guò)減少LXR蛋白（肝臟X受體）活性使老鼠體內(nèi)膽固醇在巨噬細(xì)胞內(nèi)堆積,，這是一種免疫細(xì)胞,。
LXR負(fù)責(zé)將膽固醇運(yùn)輸出巨噬細(xì)胞。當(dāng)充滿膽固醇后,，巨噬細(xì)胞將產(chǎn)生大量阻塞血管的血小板,。SIRT1能提高LXR的活性，因此膽固醇將被輸送出巨噬細(xì)胞,，并由HDL清除出體外,。（教育部科技發(fā)展中心）
原文鏈接：http://www.physorg.com/news111331848.html
原始出處：
Molecular Cell, Vol 28, 91-106, 12 October 2007
Article
SIRT1 Deacetylates and Positively Regulates the Nuclear Receptor LXR
Xiaoling Li,1,2 Songwen Zhang,1,3 Gil Blander,1 Jeanette G. Tse,1 Monty Krieger,1 and Leonard Guarente1,
1 Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
Corresponding author
Leonard Guarente
[email protected]
The NAD+-dependent deacetylase Sir2 regulates life span in lower eukaryotes. The mammalian ortholog SIRT1 regulates physiological processes including apoptosis, fat metabolism, glucose homeostasis, and neurodegeneration. Here we show that SIRT1 is a positive regulator of liver X receptor (LXR) proteins, nuclear receptors that function as cholesterol sensors and regulate whole-body cholesterol and lipid homeostasis. LXR acetylation is evident at a single conserved lysine (K432 in LXRα and K433 in LXRβ) adjacent to the ligand-regulated activation domain AF2. SIRT1 interacts with LXR and promotes deacetylation and subsequent ubiquitination. Mutations of K432 eliminate activation of LXRα by this sirtuin. Loss of SIRT1 in vivo reduces expression of a variety of LXR targets involved in lipid metabolism, including ABCA1, an ATP-binding cassette (ABC) transporter that mediates an early step of HDL biogenesis. Our findings suggest that deacetylation of LXRs by SIRT1 may be a mechanism that affects atherosclerosis and other aging-associated diseases.
