Abstract
Adipose differentiation-related protein (ADRP) is a major protein localized at the lipid droplets in macrophage-derived foam cells or liver cells. However, the role of ADRP during regression of lipid-storing cells has not been understood. When J774 macrophages were incubated for 3 days with VLDL, their content of ADRP and triacylglycerol (TG) increased 3- and 4-fold, respectively. Induction of ADRP was observed by loading lipids in macrophages with either oleic acid, suggesting that the induction ADRP induction was not receptor-dependent. ADRP expression during TG accumulation was also induced in oleic acid-treated HuH-7 human liver cells. As TG decreased in the foam cells by treatment with triacsin C, an acyl-CoA synthase inhibitor, for 6 h, ADRP protein decreased in parallel. Treatment of lipid-stored HuH-7 cells with triacsin C also reduced ADRP, indicating that ADRP reduced during regression of the lipid-storing cells. Such decrease in ADRP during regression of TG-storing cells was abolished by co-incubation with a proteasome inhibitor. Poly-ubiquitinated ADRP was detected by a pull-down experiment in the presence of the proteasome inhibitor. In addition, the proteasome inhibitor reversed not only the degradation of ADRP but TG loss by triacsin C in HuH-7 cells. The amount of ADRP is reciprocally regulated with the lipid content in the cells, and the ubiquitin-proteasome system is involved in degradation of ADRP during regression of lipid-storing cells.
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Itabe, H., Masuda, Y., Sasabe, N., Kitazato, K., Arai, H., Takano, T. (2008). Regulation of Intracellular Lipid Storage and Adipose Differentiation-Related Protein (ADRP). In: Miyazaki, A., Imawari, M. (eds) New Frontiers in Lifestyle-Related Diseases. Springer, Tokyo. https://doi.org/10.1007/978-4-431-76428-1_9
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DOI: https://doi.org/10.1007/978-4-431-76428-1_9
Publisher Name: Springer, Tokyo
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