The effect of drugs on lipoprotein lipase variants
Date Issued
2004
Date
2004
Author(s)
Hung, Min-Pao
DOI
zh-TW
Abstract
Lipoprotein lipase (LPL) plays an important role in the metabolism of plasma lipid. It catalyzes the hydrolysis of triglycerides from very low density lipoprotein (VLDL) and chylomicrons into glycerol, diacylglycerol and free fatty acid. Free fatty acid could be used as energy or re-esterified in peripheral tissues for storage. Thus, if there was any defect in LPL, the metabolism of lipid wouldn’t be under control and it’s could cause Type I hyperlipoproteinemia. Furthermore, it is also related to many diseases including obesity, coronary heart disease (CHD), pancreatitis and atherosclerosis. Therefore, LPL defects play an important role in cardiovascular diseases.
Gene deficiency may cause the change of lipoprotein lipase, including of mutation, insertion and deletion. The mutation may affect the transcription and translation. In our previous study, mutations of leucine to valine and leucine to arginine at amino acid residue 252 of LPL were found in hypertriglyceridemic Taiwanese.The expression of mRNA of the mutants LPL is the same as while the wild type. The activity and mass of lipoprotein lipase of mutants were lower than those of wild type. This indicated that the mutation did not affect the transcription of LPL but affected the process of protein synthesis. Furthermore, in order to evaluate the effect of drugs on the expression of mutated LPL, natural compounds, such as curcumin and esculetin, and the lipid-lowering drugs were used. The results indicated that fibrates could not increase the transcription of LPL both in wild type and mutant type which were previously constructed without PPRE (peroxisome proliferators-activated receptors element), but the drugs can raise the activity and the concentration of LPL in HEK293 cells. Both curcumin and esculetin have the same results as fibric acid derivatives. It suggests that curcumin and esculetin may have the same mechanism as fibric acid derivatives on LPL translation. In order to confirm the effect of drugs on the expression of LPL, the plasmids with PPRE of LPL promoter are needed. In the future, combining with gene therapy may be a good policy to treat the Type I hyperlipoproteinemia.
Subjects
脂蛋白解脂酶
PPRE
fibric acid
lipoprotein lipase
PPAR
hypertriglyceridemia
SDGs
Type
other