Magnolol induces the distributional changes of p160 and adipose differentiation-related protein in adrenal cells.
Magnolol stimulates adrenal steroidogenesis and induces the distributional changes of p160 and adipose differentiation-related protein (ADRP) in rat adrenal cells. This study investigated the underlying signaling mechanisms involved in these processes. Magnolol (30 microM) caused a time-dependent increase in the phosphorylation of extracellular signal-related kinase (ERK) in cultured adrenal cells. The following evidence supports a link between ERK activation and p160 translocation. First, the magnolol-induced redistribution of p160 from the lipid droplet surface to the cytosol, resulting in the decrease in the percentages of p160-positive cells, and this decrease in p160-positive cells was completely blocked by pretreatment with either of the MAPK-ERK kinase (MEK) inhibitors PD98059 or U0126. Second, magnolol did not significantly decrease total p160 protein levels but caused an increase in threonine phosphorylation of p160, which reached a maximum after 5 min of magnolol treatment, and this magnolol-induced phosphorylation of p160 was prevented by pretreatment with U0126, suggesting the involvement of ERK. In addition, magnolol decreased both ADRP immunostaining intensity at the lipid droplet surface and the percentage of ADRP-positive cells. This was further confirmed biochemically by the decrease in ADRP levels in total cell homogenates and in lipid droplet fractions. Magnolol-induced decrease in ADRP staining at the lipid droplet surface was not affected by pretreatment with PD98059 or U0126, indicating that ERK signaling was not involved in this event. Furthermore, treatment with 30 microM magnolol for 6 h resulted in about 50% decrease in ADRP protein level. Therefore, decreased protein levels of p160 and ADRP at the lipid droplet surface induced by magnolol were mediated via two different mechanisms: phosphorylation of p160 and downregulation of ADRP expression, respectively.
Chien
Chung-Liang
CL
Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, 1-1 Jen-Ai Road, Taipei, 100, Taiwan.
Chen
Yung-Chia
YC
Chang
Ming-Fong
MF
Greenberg
Andrew S
AS
Wang
Seu-Mei
SM
D000311:Adrenal Glands / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D051548:Histone Acetyltransferases; D017705:Lignans / Q000494:pharmacology*; D050356:Lipid Metabolism; D008387:Marine Toxins; D008565:Membrane Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009570:Nitriles / Q000494:pharmacology; D056920:Nuclear Receptor Coactivator 1; D010080:Oxazoles / Q000494:pharmacology; D000070780:Perilipin-2; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D011714:Pyrans / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013141:Spiro Compounds / Q000494:pharmacology; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*
D001713:Biphenyl Compounds; D002070:Butadienes; D004791:Enzyme Inhibitors; D005419:Flavonoids; D017705:Lignans; D008387:Marine Toxins; D008565:Membrane Proteins; D009570:Nitriles; D010080:Oxazoles; D000070780:Perilipin-2; C000602984:Plin2 protein, rat; D011714:Pyrans; D013141:Spiro Compounds; D014157:Transcription Factors; C113580:U 0126; C005498:magnolol; C053079:tautomycin; C059041:calyculin A; D051548:Histone Acetyltransferases; D056920:Nuclear Receptor Coactivator 1; D048049:Extracellular Signal-Regulated MAP Kinases; D010749:Phosphoprotein Phosphatases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one