Effect of fungal metabolites cytochalasans on lipid droplet formation in mouse macrophages.
Effects of seven cytochalasans including cytochalasins B, D and E and novel phenochalasins A and B were tested on cytosolic lipid droplet formation and neutral lipid synthesis in mouse peritoneal macrophages. Phenochalasin A inhibited lipid droplet formation in a dose-dependent manner at least up to 20 microM without any morphological changes in macrophages. Cytochalasins D and E also inhibited lipid droplet formation only in a narrow range of concentrations, around 1 and 0.1 microM, respectively. At higher concentrations they gave morphological changes in macrophages. The other four cytochalasans only showed severe morphological changes in macrophages. Phenochalasin A and cytochalasins D and E inhibited cholesteryl ester (CE) synthesis specifically with IC50 values of 0.61, 2.4 and 0.20 microM, respectively, while the other cytochalasans inhibited both CE and triacylglycerol syntheses. Thus, among the cytochalasans tested, phenochalasin A showed very specific inhibition of CE synthesis and gave the lowest morphological changes in macrophages, resulting in the best inhibitor of lipid droplet formation in macrophages.
Namatame
I
I
Graduate School of Pharmaceutical Sciences, Kitasato University, and Research Center for Biological Function, The Kitasato Institute, Tokyo, Japan.
Tomoda
H
H
Arai
M
M
Omura
S
S
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000096:biosynthesis*; D003572:Cytochalasins / Q000494:pharmacology*; D005260:Female; D008055:Lipids / Q000096:biosynthesis*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D013329:Structure-Activity Relationship
D002788:Cholesterol Esters; D003572:Cytochalasins; D008055:Lipids