Viscosity regulates apolipoprotein A-1 gene expression in experimental models of secondary hyperlipidemia and in cultured hepatocytes.
This study analyzes the relationship of plasmatic colloid osmotic pressure (PCO) and viscosity with the different hyperlipidemic stages observed in rats with acute liver damage induced by carbon tetrachloride (CCl4) and in rats with nephrotic syndrome induced by puromycin amino nucleoside (PAN). In both animal models viscosity increases were associated with the induction of the hyperlipidemic stage characterized by an increase of high density lipoproteins (HDL) and steady-state levels (SSL) of apo A-1 mRNA. In both animal models PCO decreased at early stages of the disease when hyperlipidemia was characterized principally by an increase of total cholesterol and triacylglycerols, but was not associated with the induction of HDL and apo A-1 mRNA. To confirm the in vivo findings, we studied the effect of viscosity on apo A-1 gene expression in an in vitro model using cultured hepatocytes. When medium viscosity was maintained below physiological values, an induction of the SSL of apo A-1 mRNA was observed. By contrast, when medium viscosity was raised to values similar or higher than the physiological range, the SSL of apo A-1 mRNA decreased steadily and after 24 h incubation an almost total inhibition was observed. These results suggest that in both experimental animal models of secondary hyperlipidemia, small viscosity changes below the physiological range, most probably in the interstitial fluid, can induce apo A-1 gene expression at the mRNA level, and that when viscosity reaches physiological values, apo A-1 gene expression is inhibited. Both effects were shown in cultured hepatocytes.
Nuño
P
P
Institute of Molecular Biology in Medicine, C.U.C.S. Universidad de Guadalajara, Jalisco, Mexico.
Hernández
A
A
Mendoza-Figueroa
T
T
Panduro
A
A
D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics*; D002251:Carbon Tetrachloride / Q000633:toxicity; D002478:Cells, Cultured; D003102:Colloids; D003470:Culture Media; D005786:Gene Expression Regulation; D006949:Hyperlipidemias / Q000209:etiology / Q000235:genetics*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008115:Liver Regeneration; D008297:Male; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000150:complications; D009997:Osmotic Pressure; D011692:Puromycin Aminonucleoside / Q000633:toxicity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014783:Viscosity
D016632:Apolipoprotein A-I; D003102:Colloids; D003470:Culture Media; D012333:RNA, Messenger; D011692:Puromycin Aminonucleoside; D002251:Carbon Tetrachloride