Journal of Veterinary Medical Science | |
Host Cholesterol Synthesis Contributes to Growth of Intracellular Toxoplasma gondii in Macrophages | |
Ikumi SHIGA1  Jun HIASA1  Kyohko KAMEYAMA1  Yoshifumi NISHIKAWA1  Hany M. IBRAHIM1  Xuenan XUAN1  | |
[1] National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine | |
关键词: cholesterol; lipid metabolism; macrophage; parasitology; Toxoplasma gondii; | |
DOI : 10.1292/jvms.10-0496 | |
学科分类:兽医学 | |
来源: Japanese Society of Veterinary Science | |
【 摘 要 】
References(27)Cited-By(9)The intracellular protozoan Toxoplasma gondii lacks the ability to synthesize sterol and scavenges cholesterol from the low-density lipoprotein receptor (LDLR) pathway of its host to facilitate replication. Sterol biosynthesis inhibitors, however, have a demonstrated anti-Toxoplasma effect. In this study, we examined the host mevalonate pathway as a novel source of cholesterol for T. gondii and its effects on parasite growth in macrophages. Parasite growth did not significantly change in the absence of LDLR or when LDL was exogenously supplemented. Lovastatin and compactin, both inhibitors of hydroxymethylglutaryl-CoA (HMG-CoA) reductase in the mevalonate pathway, significantly inhibited T. gondii growth in both wild-type and LDLR-knockout macrophages. Parasite growth was also suppressed by squalestatin, an inhibitor of squalene synthase, despite mevalonate producing isoprenoid intermediates in host cells. The present study demonstrates that lovastatin, compactin and squalestatin have anti-Toxoplasma activities and that the host cholesterol synthesis may contribute to parasite growth in macrophages.
【 授权许可】
Unknown
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