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Biomedical subjects

D Kaul

Publications and source records attributed to D Kaul.

At least 55 records · Page 3Linked to original sources
PubMed1992

Molecular link between membrane cholesterol and Na+/H+ exchange within human platelets.

Incubation of human platelets with cholesterol-poor, cholesterol-normal and cholesterol-rich liposomes revealed that: (i) acquisition or depletion of platelet membrane cholesterol was highly selective; (ii) variation in membrane cholesterol was highly selective. Variation in membrane cholesterol content (cholesterol-to-phospholipid molar ratio from 0.15-1.2) with respect to values found in unmodified normal platelets, was paralleled by the observed changes in amiloride-sensitive cytoplasmic pH, as well as phospholipase A2 activity. However, a decrease in cytoplasmic pH was accompanied by an increase in phospholipase A2 activity; (iii) membrane cholesterol-modulated changes in intra-platelet pH, as well as phospholipase A2 activity, was completely inhibited when platelets were pretreated with quinacrine (a specific phospholipase A2 inhibitor) before exposure to various types of liposomes. Although exposure of platelets (pretreated with amiloride) with various types of liposomes resulted in the inhibition of Na+/H+ exchange it had no noticeable effect upon the observed phospholipase A2 activity. Based upon these results we suggest that membrane cholesterol-modulated phospholipase A2 activity may be the basic mechanism responsible for the nature of Na+/H+ exchanger activity observed in cholesterol-enriched platelets, leading these platelets to a hypersensitized state.

Adenosine Triphosphate↗
PubMed1992

Molecular link between membrane cholesterol and cyclic nucleotides in human platelets.

Because of the unresolved complex role of membrane cholesterol content in platelet activity, the present study was addressed to understand two specific issues; firstly whether variation in membrane cholesterol content could influence cyclic nucleotide levels within platelets, and secondly whether the membrane cholesterol modulated cyclic nucleotide levels were mediated through phospholipase A2 activation. The results of this in vitro study revealed that membrane cholesterol not only had the inherent capacity to induce changes in the levels of cyclic nucleotides within human platelets but also that this effect was mediated through its ability to modulate phospholipase A2 activity. Based on these results we suggest that membrane cholesterol modulated phospholipase A2 activity may be the molecular link between the membrane cholesterol content and cyclic nucleotides within human platelets.

Adenosine Triphosphate↗
PubMed1991

Nature of aortic smooth muscle cellular activity induced by cholesterol incorporation through an LDL-receptor-independent pathway: preventive role of trifluoperazine on such activity.

The present study was addressed to understand two specific issues: (a) whether atherogenic activity of smooth muscle cells could be initiated by incorporating cholesterol within their membranes through a LDL-receptor-independent pathway; and (b) whether trifluoperazine, which we had recently shown to prevent the cholesterol-induced atherogenesis in an experimental animal model system, could prevent such activity of these cells induced by cholesterol in vitro. The results of such a study revealed that trifluoperazine could prevent the cholesterol-induced stimulation of (a) DNA synthesis, (b) cholesterol synthesis, (c) intracellular cGMP levels, (d) intracellular free and esterified cholesterol accumulation, and (e) collagen secretion. Furthermore, the drug caused stimulation of cholesterol-induced suppression of LDL-receptor synthesis. On this basis, we suggest that acquisition of cholesterol by smooth muscle cells through the LDL-receptor-independent pathway may be the fundamental process responsible for atherogenic activity of these cells and that the drug trifluoperazine has the inherent capacity to prevent the membrane-cholesterol-modulated atherogenic activity of smooth muscle cells in vitro.

Animals↗
PubMed1991

Alternatively spliced ltk mRNA in neurons predicts a receptor with a larger putative extracellular domain.

Ltk is a new member of the ros/insulin receptor family of tyrosine kinases that is expressed in murine B-lymphocyte precursors and forebrain neurons. We previously reported that lymphoid ltk cDNAs predict a 69 kDa transmembrane glycoprotein, which uses a CUG translational start codon and has a 110 amino acid putative extracellular domain. We now show that the predominant ltk mRNA in brain is alternatively spliced and predicts a protein with a substantially larger extracellular part. The human ltk gene maps to chromosome 15, bands q13-21, a region containing the breakpoint of a recurring chromosomal abnormality in B-cell non-Hodgkin lymphomas.

Amino Acid Sequence↗
PubMed1990

Effect of trifluoperazine on DNA and LDL-receptor synthesis in smooth muscle cells exposed to hypercholesterolemic medium in vitro.

We recently demonstrated that calmodulin and/or protein kinase C may play a crucial role in cholesterol-induced atherogenesis in experimental animal model system. The present study, which was undertaken to elucidate the effect of trifluoperazine (known as a potent inhibitor of calmodulin and protein kinase C) on DNA and LDL-receptor synthesis of aortic smooth muscle cells exposed to hypercholesterolemic medium, revealed that (a) trifluoperazine at a concentration of 25 microM caused an approximately threefold increase in the [35S]methionine-incorporated LDL-receptor protein as compared with values found in control cells; (b) the drug at concentrations greater than or equal to 0.1 microM caused inhibition of DNA synthesis as compared with values found in control cells. These results demonstrate that the preventive effect of trifluoperazine on the atherogenic activity of smooth muscle cells may be due to its ability to increase LDL-receptors synthesis as well as concomitant inhibitory action on DNA synthesis of smooth muscle cells exposed to hypercholesterolemic medium.

Animals↗
PubMed1990

Effect of trifluoperazine on cholesterol metabolism of smooth muscle cells exposed to hypercholesterolemic medium in vitro.

We recently demonstrated that the preventive effect of trifluoperazine (a potent inhibitor of calmodulin, protein kinase C, and phospholipase A2) on cholesterol-induced atherogenic activity of smooth muscle cells was mediated through its ability to inhibit smooth muscle cellular DNA synthesis coupled with stimulation of LDL receptor synthesis. The present study addressed the effect of trifluoperazine on cholesterol metabolism of aortic SMCs enriched with cholesterol through the nonreceptor pathway and revealed that (a) TFP caused inhibition of cholesterol synthesis compared with control cells bathed with hypercholesterolemic medium alone. (b) The drug also caused inhibition of free cholesterol and cholesteryl ester accumulation within smooth muscle cells compared to control cells. These results demonstrate that the preventive effect of TFP on atherogenic activity of smooth muscle cells may also be due to its ability to affect the altered/modified cholesterol metabolism of smooth muscle cells exposed to hypercholesterolemic medium in vitro.

Animals↗
PubMed1990

Effect of trifluoperazine and colchicine on smooth muscle cellular proliferative and secretory activity induced by hypercholesterolemic medium in vitro.

The present study, addressed to understand the mechanism behind the cholesterol-induced proliferative and collagen secretory activity of smooth muscle cells, revealed that cholesterol-induced smooth muscle cellular DNA synthesis and collagen secretion was mediated through its ability to amplify the intracellular cGMP signal because of the fact that Trifluoperazine (an anticalmodulin and blocker of phospholipase A2) and colchicine (an antitubulin and inhibitor of guanyl cyclase) inhibited DNA synthesis and collagen-secretory activity of smooth muscle cells by their ability to decrease the cGMP levels within smooth muscle cells. From these results we suggest that membrane cholesterol modulated phospholipase 'A2' activity may be the basic mechanism involved in cholesterol-induced proliferative and collagen-secretory activity of smooth muscle cells in vitro.

Animals↗
PubMed1990

Effect of anticalmodulin and antitubulin on LDL-receptor synthesis in aortic smooth muscle cells cultured in vitro.

Effect of trifluoperazine and colchicine on LDL-receptor synthesis in smooth muscle cells exposed to hypercholesterolemic medium in vitro have been studied. While trifluoperazine at 25 microM concentration caused stimulation of LDL-receptor synthesis, colchicine acted as a dose-dependent inhibitor of LDL-receptor synthesis. Thus calmodulin down regulates LDL-receptor synthesis independent of microtubular involvement.

Animals↗
PubMed1989

Preventive effect of trifluoperazine on atherosclerosis induced by cholesterol & adrenaline in rabbits.

Studies on the preventive role of trifluoperazine on cholesterol and adrenaline-induced experimental atherosclerosis in rabbits, revealed that trifluoperazine completely prevented the development of atherosclerotic lesions in both the aorta and coronary arteries of animals administered atherogenic diet and adrenaline (im) despite the fact that this drug had no significant effect on the elevated serum lipid profile induced by atherogenic diet. These findings confirm earlier observations of the authors that trifluoperazine has an inherent capacity to prevent atherogenesis.

Animals↗
PubMed1987

Atherogenesis. Preventive action of trifluoperazine.

This preliminary note describes the preventive action of trifluoperazine against cholesterol-induced atherosclerosis in rabbits. Although this drug had no significant effect on the elevated levels of serum lipids induced by the atherogenic diet, it completely inhibited the initiation of atherosclerotic lesions in rabbits fed atherogenic diets. Based on these findings, we propose that calmodulin and protein kinase 'C' may play a key role in the development of the atherosclerotic process.

Animals↗
PubMed1987

Elucidation of the receptors in macrophage and Plasmodium yoelii interactions.

Binding of hyperimmune serum opsonized merozoites of Plasmodium Yoelii nigerensis to trypsinized macrophages suggested it to be mediated by FcII receptor. Receptor blocking inhibition with monoclonal antibody 2.4G2 directed against Fc receptor for IgG1/IgG2b provided evidence that Fc delta 2b on macrophage played an important role in the merozoite-macrophage interactions. In addition, a neuraminidase sensitive receptor was noted to mediate the binding of P. yeelii merozoites in the absence of serum. Binding inhibition studies with two monosaccharides, D-mannose and alpha-methyl mannoside, indicated the role of Mannose/Fucose receptor on macrophage in this interaction.

Animals↗
PubMed1983

Atherosclerosis: a molecular disease of membrane fusion.

A working thermodynamic-hysteresis concept, which serves to simplify and clarify the general mechanism behind membrane fusion processes involved in health and disease, is proposed. It is suggested that this concept not only possesses the inherent capacity to answer some fundamental questions involved in Atherosclerosis but also may be even more useful in defining an outline of "Molecular Pathology" for future investigation.

Arteriosclerosis↗
PubMed1980

Micellar organization of lipid droplets in human atherosclerotic lesions.

Low-angle diffraction studies on lipid droplets from human atherosclerotic lesions showed 3 characteristic reflections at 96 A, 72 A and 36 A. These reflections could best be accounted for by the consideration of a lamellar model containing globular esterified cholesterol micelles (36 A) surrounded by globular micelles (45--46 A) composed of a phospholipid-cholesterol complex.

Arteriosclerosis↗