期刊
BLOOD
卷 116, 期 11, 页码 1857-1866出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2009-12-256461
关键词
-
类别
资金
- Italian Telethon
- European Leukodystrophy Association
- EU [241622]
- Italian Ministry of Health [ex 56-05-16]
- Cariplo Foundation
- National Institutes of Health [GM069338]
The balance between survival and death in many cell types is regulated by small changes in the intracellular content of bioactive sphingolipids. Enzymes that either produce or degrade these sphingolipids control this equilibrium. The findings here described indicate that the lysosomal galactocerebrosidase (GALC) enzyme, defective in globoid cell leukodystrophy, is involved in the maintenance of a functional hematopoietic stem/progenitor cell (HSPC) niche by contributing to the control of the intracellular content of key sphingolipids. Indeed, we show that both insufficient and supraphysiologic GALC activity-by inherited genetic deficiency or forced gene expression in patients' cells and in the disease model-induce alterations of the intracellular content of the bioactive GALC downstream products ceramide and sphingosine, and thus affect HSPC survival and function and the functionality of the stem cell niche. Therefore, GALC and, possibly, other enzymes for the maintenance of niche functionality and health tightly control the concentration of these sphingolipids within HSPCs. (Blood. 2010; 116(11): 1857-1866)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据