Disease relevance of Mttp

• Despite a complete lack of microsomal triglyceride transfer protein (MTP), L35 rat hepatoma cells secrete triglyceride-containing lipoproteins, albeit at a rate 25% of that of parental FAO hepatoma cells, which express high levels of MTP [1].
• Decreased microsomal triglyceride transfer protein activity contributes to initiation of alcoholic liver steatosis in rats [2].
• BACKGROUND/AIMS: To elucidate the role of microsomal triglyceride transfer protein (MTP) in the pathogenesis of alcoholic fatty liver, the effects of ethanol on MTP activity and gene expression were investigated [2].

High impact information on Mttp

• Unexpectedly, protease inhibitors also inhibited the secretion of apolipoprotein B. This was associated with inhibition of cholesteryl-ester synthesis and microsomal triglyceride transfer-protein activity [3].
• The results showed that apoB-53 could be expressed in HeLa cells with or without expression of MTP [4].
• Enhanced expression of hepatic acyl-coenzyme A synthetase and microsomal triglyceride transfer protein messenger RNAs in the obese and hypertriglyceridemic rat with visceral fat accumulation [5].
• Exposure of HepG2 cells to low concentrations of ethanol reduced MTP mRNA levels in a concentration- and time-dependent manner [6].
• Transient transfection analysis of human MTP promoter-driven luciferase gene expression showed that ethanol down-regulates MTP promoter activity in a manner parallel to that observed for mRNA levels [6].

Biological context of Mttp

• Stable expression of a MTP transgene restored the secretion of both apoB-100 and apoB-48 in L35 cells, indicating that MTP is essential for the secretion of both forms of apoB [1].
• Previously, based on distinct requirement of microsomal triglyceride transfer protein (MTP) and kinetics of triglyceride (TG) utilization, we concluded that assembly of very low density lipoproteins (VLDL) containing B48 or B100 was achieved through different paths (Wang, Y. , McLeod, R. S., and Yao, Z. (1997) J. Biol. Chem. 272, 12272-12278) [7].
• This inhibition of fatty change by hrHGF was accompanied by recovery of MTP activity and gene expression [2].
• Long-term dietary supplementation of fresh garlic may exert a lipid-lowering effect partly through reducing intestinal MTP gene expression, thus suppressing the assembly and secretion of chylomicrons from intestine to the blood circulation [8].
• Deletion analysis suggested that the MTP promoter sequence contains a negative ethanol response element -612 to -142 bp upstream of the transcription start site [6].

Anatomical context of Mttp

• Identification of microsomal triglyceride transfer protein in intestinal brush-border membrane [9].
• Based on cell fractionation, early studies have suggested the endoplasmic reticulum (ER) as the exclusive site of MTP [9].
• The treatment of Caco-2 cells with nocodazole and colchicine blocked the appearance of MTP in the apical membrane [9].
• In conclusion, the present studies suggest that MTP is present in the brush-border membrane of the enterocyte [9].
• Western blot analysis and biochemical activity measurement confirmed MTP protein expression in brush-border membrane vesicles (BBMV) isolated from the intestinal epithelial cells of various species [9].

Associations of Mttp with chemical compounds

• Since apoB18 does not assemble triglyceride-rich lipoproteins, these studies suggest that apoB may interact with MTP before its lipidation [10].
• Binding of all the polypeptides to MTP was enhanced in the presence of taurocholate [10].
• Native VLDL bound poorly to MTP, but its preincubation with Tween-20 resulted in significantly increased binding to MTP [10].
• Dietary oxidized cholesterol decreases expression of hepatic microsomal triglyceride transfer protein in rats [11].
• Inhibition of MTP activity abolished the oleate-induced utilization of prelabeled TG (by 80%) and hB48 (by 70%) for hB48-VLDL secretion but decreased utilization of pre-existing TG (by <25%) and B100 (by 45%) for rB100-VLDL secretion to a lesser extent [12].

Physical interactions of Mttp

• Apolipoprotein B binding to microsomal triglyceride transfer protein decreases with increases in length and lipidation: implications in lipoprotein biosynthesis [10].

Regulatory relationships of Mttp

• Inhibition of the microsomal triglyceride transfer protein blocks the first step of apolipoprotein B lipoprotein assembly but not the addition of bulk core lipids in the second step [13].

Other interactions of Mttp

• Microsomal triglyceride transfer protein (MTP), a heterodimer of 97 kDa and protein disulfide isomerase, is required for the assembly of apolipoprotein B (apoB)-containing triglyceride-rich lipoproteins [10].

Analytical, diagnostic and therapeutic context of Mttp

• Equal levels of MTP were also apparent in the livers of all groups of animals, as measured by immunoblotting with an anti-MTP antiserum [14].
• The present study was designed to investigate the relationship between MTP expression and chylomicron assembly in an insulin resistant non-diabetic animal model [15].
• Hepatic microsomal triglyceride transfer protein activity scaled to liver weight and metabolic body size was 2.69, 3.36, 4.58, 5.83, 7.49, and 22.3 nmole triolein transferred in the liver/min/kg body weight0.75 for the rabbit, guinea pig, rat, hen, cow, and sow, respectively [16].

References