PubMed Health⌕ Search

Biomedical subjects

S S Alam

Publications and source records attributed to S S Alam.

12 recordsLinked to original sources
PubMed1999

Genomic structure of the rat major AP endonuclease gene (Apex) with an adjacent putative O-sialoglycoprotease gene (Prsmg1/Gcpl1) and a processed Apex pseudogene (Apexp1).

Genomic sequencing and chromosomal assignment of the gene encoding rat APEX nuclease, a multifunctional DNA repair enzyme, were performed. An active Apex gene and a processed pseudogene were isolated from a rat genomic library. The active Apex gene consists of 5 exons and 4 introns spanning 2.1 kb. The putative promoter region of the Apex gene lacks the typical TATA box, but contains CAAT boxes and a CpG island having putative binding sites for several transcription factors, such as Sp1, AP-2, GATA-1 and ATF. A putative O-sialoglycoprotease (a homologue of Pasteurella haemolytica glycoprotease, gcp; abbreviated as Prsmg1/Gcpl1) gene consisting of 11 exons and 10 introns spanning 7.3 kb lies immediately adjacent to the Apex gene in a 5'-to-5' orientation. The Apex gene locus was mapped to rat chromosome 15p12 using in situ hybridization. The processed pseudogene (designated as rat Apexp1) has a nucleotide sequence 87.1% identical to that of the rat Apex cDNA, although several stop codons interrupting the coding sequences and multiple nucleotide deletions were observed. The Apexp1 is located in an inactive LINE sequence. Calculation of nucleotide substitution rates suggests that the immediate, active progenitor of Apexp1 arose 23 million years ago and that the non-functionalization occurred 15 million years ago.

Animals↗
PubMed1985

Enhancement of cholesteryl ester metabolism in cultured human monocyte-derived macrophages by verapamil.

The effect of the Ca2+ entry blocker, verapamil, on the biosynthesis of cholesterol and the metabolism of low-density lipoprotein (LDL) was studied in cultured human monocyte-derived macrophages. Addition of verapamil (50 microM) of monocyte-derived macrophages enhanced 125I-LDL and 125I-labelled acetyl-LDL binding and internalization, and increased [2-14C]acetate incorporation into cholesterol. Since higher levels of LDL and modified lipoproteins may be implicated in atherogenesis, the more efficient processing of these lipoproteins by monocyte-derived macrophages in the presence of Ca2+ blocker warrants further assessment for its potential as an antiatherogenic agent.

Cholesterol↗
PubMed1983

Regulation of cholesterol synthesis by plasma lipoproteins from patients with abetalipoproteinemia.

Despite a complete lack of apoprotein B-containing lipoproteins from the plasma of patients with abetalipoproteinemia, rates of cholesterol synthesis measured in vivo or in freshly isolated cells in vitro are not markedly elevated. These observations suggest that other lipoprotein particles present in the plasma of patients with abetalipoproteinemia may regulate cellular cholesterol synthesis in this disorder. In the present report we have studied the effects of lipoprotein fractions from plasma of normal subjects, patients with abetalipoproteinemia, and a patient with Type III hyperlipoproteinemia on cholesterol synthesis in cultured human fibroblasts. LDL from normal subjects or the HDL2 fraction from the plasma of patients with abetalipoproteinemia were effective inhibitors of cholesterol synthesis (greater than 75% inhibition at 20 micrograms protein/ml) whereas HDL3 from normal or abetalipoproteinemia plasma stimulated cholesterol synthesis. Rates of cholesterol synthesis in fibroblasts from a patient with receptor-negative homozygous familial hypercholesterolemia were only minimally reduced by prior incubation in media containing either normal LDL or HDL2 from the plasma of a patient with abetalipoproteinemia. We conclude that lipoproteins present in the HDL2 fraction of plasma from patients with abetalipoproteinemia (which are relatively rich in apoprotein E) are effective regulators of cholesterol synthesis in normal human fibroblasts and that this regulation is mediated by an interaction of these lipoproteins with the LDL (B, E) receptor. These in vitro findings may explain why rates of cholesterol synthesis are not markedly elevated in patients with abetalipoproteinemia studied in vivo.

Abetalipoproteinemia↗
PubMed1983

Lipoprotein lipase and hepatic lipase activity after heparin administration in abetalipoproteinemia and hypobetalipoproteinemia.

The purpose of this study was to examine whether an absence of triglyceride-rich lipoproteins (chylomicrons and very-low-density lipoproteins) in plasma is associated with any changes in the enzyme activity of lipoprotein lipase or hepatic lipase after heparin administration. To study this, the activities of hepatic lipase and lipoprotein lipase were determined in control subjects, in two patients with heterozygous hypobetalipoproteinemia, and in three patients with phenotypic abetalipoproteinemia after administration of heparin. Both enzymes showed normal activity in the patients with hypobetalipoproteinemia, but showed consistently reduced activity in the patients with abetalipoproteinemia. Hepatic lipase activity in plasma samples from these three patients obtained 15 minutes after intravenous injection of heparin was 55%, 87%, and 46% of that of the controls, whereas corresponding values in plasma samples obtained 30 minutes after heparin were 47%, 70%, and 57%, respectively. Lipoprotein lipase activity in the three patients with abetalipoproteinemia was 46%, 29%, and 34% of that of the controls in the samples obtained 15 minutes after heparin injection, whereas the values obtained after 30 minutes were 53%, 64%, and 47% of that of the controls. We conclude that an inherent absence of triglyceride-rich lipoproteins, as occurs in abetalipoproteinemia, is associated with reduced enzyme activity of both hepatic lipase and lipoprotein lipase in plasma after heparin administration.

Abetalipoproteinemia↗
PubMed1982

Dimethyl sulfoxide as a cholesterol-lowering agent in cultured fibroblasts exposed to low density lipoproteins.

Confluent cultures of human skin fibroblasts were exposed to medium containing high levels of low density lipoproteins (LDL-cholesterol equivalent to 400 micrograms per ml) and 0 or 2% dimethyl sulfoxide (DMSO). The uptake and accumulation of cellular cholesterol from LDL were reduced significantly (30%) in the DMSO-treated cells as compared to the controls. The reduction in cellular sterol was due almost exclusively to a significant decrease (50%) in cholesterol ester accumulation. Incubation of cells with 125I-labelled LDL showed clearly that DMSO did not act by increasing the secretion of cholesterol from the cell, but rather by significantly decreasing the binding, internalization and degradation of exogenous LDL. De novo synthesis of cholesterol from [14C]acetate was measured and found to correlate inversely with cellular sterol levels in either control or DMSO-treated cells.

Acetates↗
PubMed1981

Effects of long-term protein deficiency on plasma lipoprotein concentrations and metabolism in rhesus monkeys.

Lipoprotein concentrations and metabolism were studied in 5- and 9-year-old rhesus monkeys (Macaca mulatta). Both age groups had been divided into control (13.8% of the calories as protein) and low-protein (3.7% protein) subgroups at birth. All were tested before and after their dietary lipid was changed from corn oil to butter plus cholesterol. The concentrations of very-low-density and high density2 lipoproteins (VLDL and HDL2) tended to be higher in monkeys of the low-protein group, and butter plus cholesterol accentuated the difference. All monkeys of the low protein group had elevated levels of at least one of these two classes of lipoproteins. The secretion of nascent VLDL (after intravenous Triton WR-1339) was greater in the low protein than in the control group when both were fed butter plus cholesterol, and rates of VLDL secretion showed a strong positive correlation with the fasting levels of VLDL. Thirty minutes after the intravenous administration of heparin, VLDL triglyceride was almost completely removed, and the apolipoprotein was reduced by 40%; VLDL cholesteryl esters were unchanged. There was a simultaneous decrease in the intermediate density lipoproteins (IDL) and an increase in HDL2, but the low density lipoproteins (LDL) and HDL2 did not change. The rate of VLDL protein removal from plasma was greater in the low protein than in the control group, and the rates for individual monkeys correlated with the levels of VLDL and HDL2 prior to heparin administration. Hepatic postheparin lipase measured in vitro with saturating levels of substrate was significantly higher in the plasma of control than in that of low protein monkeys.

Animals↗
PubMed1980

The mass uptake of cholesterol ester from low density lipoproteins by cultured smooth muscle and adventitial cells of human aortas.

Cultured human smooth muscle and adventitial cells were incubated with human serum and low density lipoprotein (LDL) to study the uptake and accumulation of cholesterol ester from exogenous LDL. The cellular total cholesterol varied with the amount of LDL cholesterol in the medium. The cholesterol ester content increased 4-fold after 2 hours of incubation. A 6-fold rise occurred by 24 hours and continued to 72 hours. The cholesterol ester of the adventitial cells was markedly depleted by incubation with abetalipoproteinemic serum or with a lipid-depleted plasma fraction. By the use of 14C-labeled LDL free cholesterol in the incubation medium, we calculated that some 70-80% of the total accumulated cholesterol ester after 24 hours of incubation was derived from LDL cholesterol ester, and only 20-30% was synthesized by the cells. These studies demonstrated conclusively that human cells greatly increase their cholesterol ester mass after incubation with LDL.

Aorta↗