ADRP/adipophilin is degraded through the proteasome-dependent pathway during regression of lipid-storing cells.
Adipose differentiation-related protein (ADRP) is a major protein associated with lipid droplets in various types of cells, including macrophage-derived foam cells and liver cells. However, the role of ADRP in the processes of formation and regression of these cells is not understood. When J774 murine macrophages were incubated with either VLDL or oleic acid, their content of both ADRP and triacylglycerol (TG) increased 3- to 4-fold. Induction of ADRP during TG accumulation was also observed in oleic acid-treated HuH-7 human liver cells. Addition of triacsin C, a potent inhibitor of acyl-CoA synthase, for 6 h decreased the amount of TG in VLDL-induced foam cells and oleic acid-treated liver cells; it decreased the amount of ADRP protein in parallel, indicating the amount of ADRP reduced during regression of the lipid-storing cells. Addition of a proteasome inhibitor during triacsin C treatment abolished the ADRP decrease and accumulated polyubiquitinated ADRP. In addition, the proteasome inhibitor reversed not only the degradation of ADRP but also TG reduction by triacsin C. These results suggest that cellular amounts of ADRP and TG regulate each other and that the ubiquitin-proteasome system is involved in degradation of ADRP during regression of lipid-storing cells.
Masuda
Yutaka
Y
Department of Biological Chemistry, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Itabe
Hiroyuki
H
Odaki
Miho
M
Hama
Kotaro
K
Fujimoto
Yasuyuki
Y
Mori
Masahiro
M
Sasabe
Naoko
N
Aoki
Junken
J
Arai
Hiroyuki
H
Takano
Tatsuya
T
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D019301:Oleic Acid / Q000494:pharmacology; D000070780:Perilipin-2; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014226:Triazenes / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
D018076:DNA, Complementary; D008079:Lipoproteins, VLDL; D008565:Membrane Proteins; C000602982:PLIN2 protein, human; D000070780:Perilipin-2; C000602983:Plin2 protein, mouse; D012333:RNA, Messenger; D014226:Triazenes; D014280:Triglycerides; D025801:Ubiquitin; D019301:Oleic Acid; C034613:triacsin C; D046988:Proteasome Endopeptidase Complex