生物谷報(bào)道：美國國立衛(wèi)生研究院的科研人員近日研究發(fā)現(xiàn)，限制營養(yǎng)的供應(yīng)可以阻礙肌肉干細(xì)胞發(fā)育為成熟的肌細(xì)胞,。
一直以來,，獲取營養(yǎng)物質(zhì)對于人體細(xì)胞的發(fā)育有著深遠(yuǎn)的影響是公認(rèn)的道理,，但是科學(xué)家尚不太清楚對其中的原因。此次,，研究人員通過調(diào)查葡萄糖量研究如何影響肌肉干細(xì)胞分化為成熟的骨骼肌纖維,。
研究人員發(fā)現(xiàn)，葡萄糖限制（GR）會(huì)削弱骨骼肌成肌細(xì)胞的分化,，而且會(huì)激活腺苷酸活化蛋白激酶（AMPK）,。這些結(jié)果表明了一個(gè)路徑，即對低葡萄糖水平做出響應(yīng)的AMPK的活化會(huì)刺激NAD+合成酶Nampt的表達(dá),。已知NAD+是SIRT1 的一種輔助因子,，后者在眾多生理過程中扮演著一個(gè)重要的角色，包括骨骼肌細(xì)胞的分化,，而且還牽扯到了壽命和衰老的調(diào)整。重要的是,，抑制AMPK,、Nampt或 SIRT1導(dǎo)致骨骼肌細(xì)胞不介意一個(gè)營養(yǎng)不良的環(huán)境，而且可以在一些本不適合的環(huán)境下分化,。
這些結(jié)果表明了一個(gè)響應(yīng)低營養(yǎng)環(huán)境,、積極地控制肌肉分化的詳細(xì)路徑。研究人員推測,，AMPK-Nampt-SIRT1路徑的作用就像一個(gè)細(xì)胞檢查站,，它可能被營養(yǎng)物質(zhì)供應(yīng)的減少而活化，從而阻止細(xì)胞在缺乏熱量的條件下從事需要能量的過程——諸如細(xì)胞分化,。另一方面,，一旦營養(yǎng)物質(zhì)供應(yīng)恢復(fù)，這條路徑就被關(guān)閉,，從而讓生理發(fā)育恢復(fù),。
這項(xiàng)研究的重要意義超出了細(xì)胞發(fā)育。這一機(jī)制還能在成體組織里運(yùn)作,，因此它可能成為對限制熱量攝入的節(jié)食療法的響應(yīng)的一部分,。此外，這組科學(xué)家還發(fā)現(xiàn)葡萄糖限制或者用二甲雙胍（一種用于治療II型糖尿病的藥物）治療骨骼肌細(xì)胞也有類似的結(jié)果,，而且導(dǎo)致了SIRT1的活化,。因此，糖尿病患者從降低飲食的熱量攝入中獲得的眾所周知的益處可能是由于AMPK-Nampt-SIRT1路徑活化的貢獻(xiàn),。另外,，一個(gè)具有吸引力的推測是，AMPK 和SIRT1可能被證明是用制止肌肉萎縮的破壞性效應(yīng)的合理靶標(biāo),。（生物谷www.bioon.com）
生物谷推薦原始出處：
Developmental Cell,，Vol 14, 661-673,，Marcella Fulco，Vittorio Sartorelli
Glucose Restriction Inhibits Skeletal Myoblast Differentiation by Activating SIRT1 through AMPK-Mediated Regulation of Nampt
Marcella Fulco,1 Yana Cen,2 Po Zhao,3 Eric P. Hoffman,3 Michael W. McBurney,4 Anthony A. Sauve,2 and Vittorio Sartorelli1,
1 Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, 50 South Drive, Bethesda, MD 20892, USA
2 Department of Pharmacology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
3 Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20010, USA
4 Ottawa Health Research Center Institute, 501 Smyth Road, Ottawa K1H 8L6, Canada
Summary
It is intuitive to speculate that nutrient availability may influence differentiation of mammalian cells. Nonetheless, a comprehensive complement of the molecular determinants involved in this process has not been elucidated yet. Here, we have investigated how nutrients (glucose) affect skeletal myogenesis. Glucose restriction (GR) impaired differentiation of skeletal myoblasts and was associated with activation of the AMP-activated protein kinase (AMPK). Activated AMPK was required to promote GR-induced transcription of the NAD+ biosynthetic enzyme Nampt. Indeed, GR augmented the Nampt activity, which consequently modified the intracellular [NAD+]:[NADH] ratio and nicotinamide levels, and mediated inhibition of skeletal myogenesis. Skeletal myoblasts derived from SIRT1+/− heterozygous mice were resistant to the effects of either GR or AMPK activation. These experiments reveal that AMPK, Nampt, and SIRT1 are the molecular components of a functional signaling pathway that allows skeletal muscle cells to sense and react to nutrient availability.
