The Yin and Yang of lactosylceramide metabolism: Implications in cell function

被引：70

作者：

Chatteriee, Subroto ^{[1
]}

Pandey, Ambarish ^{[2
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Pediat, Lipid Res Artherosclerosis Unit, Baltimore, MD 21205 USA

[2] All India Inst Med Sci, New Delhi 110029, India

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS | 2008年 / 1780卷 / 03期

关键词：

lactosylceramide; glycosphingolipids; gangliosides; apoptosis; signal transduction; cell proliferation; cell adhesion; angiogenesis;

D O I：

10.1016/j.bbagen.2007.08.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Although lactosylceramide (LacCer) plays a pivotal role in the biosynthesis of nearly all the major glycosphingolipids, its function in regulating cellular function has begun to emerge only recently. Our current opinion is that several physiologically critical molecules such as modified/oxidized LDL, growth factors, pro-inflammatory cytokines and fluid shear stress converge upon and activate lactosylceramide synthase to generate LacCer. In turn, LacCer activates an "oxygen-sensitive" signaling pathway involving superoxides, nitric oxide, p21 Ras GTP loading, kinase cascade, PI3kinase/Akt activation, nuclear factor up-regulation ultimately contributing to phenotypic changes such as cell proliferation, adhesion, migration and angiogenesis. Since dys-regulation of such phenotypic changes constitute a hallmark in several diseases of the cardiovascular system, proliferative disorders such as cancer, polycystic kidney disease and inflammatory diseases, LacCer synthase and LacCer provide novel targets for the development of therapeutics aimed at these health conditions. (c) 2007 Elsevier B.V.. All rights reserved.

引用

页码：370 / 382

页数：13

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