Bezafibrate attenuates the overexpression of plasminogen activator inhibitor-1 messenger RNA by a combination of mono-unsaturated fatty acid and insulin in hepG2 cells.
The effects of bezafibrate (PPAR alpha activator) and troglitazone (PPAR gamma activator) on the expression of plasminogen activator inhibitor type-1 (PAI-1) in HepG2 cells were investigated. Exposure of the cells for 24 hours to either oleic acid or insulin showed no obvious effects on PAI-1 synthesis, whereas the combination of the two agents induced a 2.3-fold increase in PAI-1 synthesis, which was accompanied by a 3-fold increase in both the 2.2 kb and 3.2 kb forms of PAI-1 mRNA. This up-regulation of PAI-1 synthesis was attenuated by bezafibrate in a dose-dependent manner (1-100 microM) with 30% reversal at 100 microM. In contrast, troglitazone further stimulated PAI-1 synthesis to 140% of the level obtained in the presence of both oleic acid and insulin. This attenuation by bezafibrate and enhancement by troglitazone required the presence of both oleic acid and insulin. It is interesting that PAI-1 expression was affected so differently by these two PPAR activators.
Suzuki
Y
Y
Department of Physiology, Hamamatsu University School of Medicine, Handa, Japan.
Urano
T
T
Ihara
H
H
Nakajima
T
T
Nagai
N
N
Takada
Y
Y
Taminato
T
T
Takada
A
A
D001629:Bezafibrate / Q000494:pharmacology*; D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism; D019301:Oleic Acid / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D000077288:Troglitazone; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation
D002839:Chromans; D017077:Culture Media, Conditioned; D004338:Drug Combinations; D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D013844:Thiazoles; D045162:Thiazolidinediones; D019301:Oleic Acid; D000077288:Troglitazone; D001629:Bezafibrate