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科学家揭示摄入高果糖的危害
作者:小柯机器人 发布时间:2020/12/25 14:38:37

美国纪念斯隆-凯特琳癌症中心Kayvan R. Keshari和Michael G. Kharas研究团队合作取得一项新成果。经过不懈努力,他们的最新研究表明在急性髓样白血病细胞中高果糖诱导了丝氨酸合成途径的开启。2020年12月22日出版的《细胞-代谢》在线发表了这项成果。

研究人员发现白血病细胞的果糖代谢可以通过靶向丝氨酸从头合成途径(SSP)来抑制。不同于高葡萄糖的情况,在富含果糖的情况下,与其对应的正常细胞相比,白血病细胞更加依赖于SSP。该代谢途径由氧化还原辅因子NAD+/ NADH的比率介导,并且增加的SSP通量有利于谷氨酰胺生成α-酮戊二酸,即使在缺乏葡萄糖的情况下,白血病细胞也可以增殖。在高果糖情况下,抑制SSP途径的限速酶PHGDH可以显著减少小鼠白血病的发病率,从而证实了SSP在白血病细胞代谢可塑性中的重要作用。

据了解,显着增加的果糖食用量被认为是癌症的潜在诱导因素。癌细胞利用果糖的代谢适应性为其恶性生长提供了优势,但尚未发现有效的治疗靶点。

附:英文原文

Title: High Fructose Drives the Serine Synthesis Pathway in Acute Myeloid Leukemic Cells

Author: Sangmoo Jeong, Angela Maria Savino, Rachel Chirayil, Ersilia Barin, Yuanming Cheng, Sun-Mi Park, Alexandra Schurer, Edouard Mullarky, Lewis C. Cantley, Michael G. Kharas, Kayvan R. Keshari

Issue&Volume: 2020-12-22

Abstract: A significant increase in dietary fructose consumption has been implicated as a potentialdriver of cancer. Metabolic adaptation of cancer cells to utilize fructose confersadvantages for their malignant growth, but compelling therapeutic targets have notbeen identified. Here, we show that fructose metabolism of leukemic cells can be inhibitedby targeting the de novo serine synthesis pathway (SSP). Leukemic cells, unlike their normal counterparts,become significantly dependent on the SSP in fructose-rich conditions as comparedto glucose-rich conditions. This metabolic program is mediated by the ratio of redoxcofactors, NAD+/NADH, and the increased SSP flux is beneficial for generating alpha-ketoglutaratefrom glutamine, which allows leukemic cells to proliferate even in the absence ofglucose. Inhibition of PHGDH, a rate-limiting enzyme in the SSP, dramatically reducesleukemia engraftment in mice in the presence of high fructose, confirming the essentialrole of the SSP in the metabolic plasticity of leukemic cells.

DOI: 10.1016/j.cmet.2020.12.005

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30660-4

 

期刊信息

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:22.415
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx