Alkylacylglycerolipid domain of GPI molecules of Leishmania is responsible for inhibition of PKC-mediated c-fos expression
Alkylacylglycerolipid domain of GPI molecules of Leishmania is responsible for inhibition of PKC-mediated c-fos expression
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DOI：
10.1194/jlr.m200296-jlr200
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发表时间：
2003-03-01
影响因子：
6.5
通讯作者：
Vishwakarma, RA
中科院分区：
文献类型：
--
作者：
Chawla, M;Vishwakarma, RA
糖基磷脂酰肌醇(GGIs)是引起多种形式利什曼病的原生动物利什曼原虫细胞膜中含量最丰富的分子。利什曼原虫的主要GPI[脂磷脂(LPG)和糖蛋白磷脂(GIPLs)]表现出的显著生物学活性之一是抑制巨噬细胞的功能，如依赖蛋白激酶C(PKC)的信号通路。利什曼原虫GPI的生物活性与激活巨噬细胞功能的布氏锥虫和恶性疟原虫GPI相反。为了解决利什曼原虫GPIs的哪个结构域导致PKC依赖的瞬时c-fos表达显著下调的问题，我们评价了化学合成的相应GPIs的烷基酰甘油脂域，以及从杜氏利什曼原虫分离的LPG和GIPLs对巨噬细胞PKC和c-fos表达的抑制作用。这些结果表明利什曼原虫不寻常的脂类结构域是抑制PKC依赖的瞬时c-fos表达的主要原因。
Glycosylphosphatidylinositols (GPIs) are the most abundant molecules present in the membranes of the parasitic protozoa Leishmania responsible for multiple forms of leishmaniasis. Among the prominent biological activities displayed by the major Leishmania GPIs [lipophosphoglycan (LPG) and glycoinositolphospholipids (GIPLs)] is the inhibition of macrophage functions such as the protein kinase C (PKC)-dependent signaling pathway. The bioactivity of Leishmania GPIs is in contrast to Trypanosoma brucei and Plasmodium falciparum GPIs, which activate the macrophage functions. To address the question as to which structural domain of Leishmania GPIs is responsible for dramatic down-regulation of PKC-dependent transient c-fos expression, the chemically synthesized defined alkylacylglycerolipids domain of corresponding GPIs, and LPG and GIPLs isolated from Leishmania donovani, were evaluated for inhibition of PKC and c-fos expression in macrophages. The results presented here demonstrate that the unusual lipid domain of Leishmania GPIs is primarily responsible for inhibition of PKC-dependent transient c-fos expression.