Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interaction of high density lipoprotein with its putative receptor stimulates translocation and efflux of intracellular sterols by a process involving activation of protein kinase C. This study shows that activation of cAMP-dependent protein kinase also stimulates efflux of intracellular sterols. When intracellular sterol pools of cholesterol-loaded cultured human skin fibroblasts and bovine aortic endothelial cells were radiolabeled with the biosynthetic precursor [3H]mevalonolactone, high density lipoprotein3 (HDL3)-mediated 3H-sterol efflux was enhanced by addition of the adenylylcyclase activator forskolin, the phosphodiesterase inhibitors theophylline and 3-isobutyl-1-methylxanthine, and the cAMP analogues N6-benzoyl-cAMP (N6-cAMP) and 8-thiomethyl-cAMP. The effect of N6-cAMP was abolished by an inhibitor of cAMP-dependent protein kinase (H8). The enhanced sterol efflux was independent of receptor binding of HDL3, as similar effects were observed in the presence of tetranitromethane-modified HDL3, which lacks receptor binding activity. N6-cAMP stimulated efflux of several subspecies of newly synthesized sterols, including cholesterol. Elevation of cAMP levels increased the proportion of radiosterols that were accessible to treatment of cells with the enzyme cholesterol oxidase, suggesting that activation of cAMP-dependent protein kinase stimulates translocation of sterols from intracellular compartments to the plasma membrane where they desorb from the cell surface. Thus, at least two distinct protein kinase signalling pathways modulate transport of intracellular sterols in cholesterol-loaded cells.
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PMID:Cyclic AMP stimulates efflux of intracellular sterol from cholesterol-loaded cells. 750 79

Cholesterol was poorly available to free apolipoprotein (apo)A-I-mediated cellular lipid efflux from cholesterol-loaded rat vascular smooth muscle cells generating cholesterol-poorer pre-beta-HDL particles than those generated from macrophages by the same reaction (Li, Q., Komaba, A., and Yokoyama, S. (1993) Biochemistry 32, 4597-4603). The factors known to induce transformation of the smooth muscle cells into a macrophage-like stage were used in order to modulate this reaction, such as human platelet-derived growth factor, macrophage colony-stimulating factor, and phorbol 12-myristate-13-acetate (PMA). When the cells were stimulated by PMA following the pretreatment with platelet-derived growth factor plus macrophage colony-stimulating factor, cholesterol efflux mediated by free apoA-I increased 3-fold without changing phospholipid efflux, resulting in generation of pre-beta-HDL particles more rich in cholesterol. This treatment had only a little or no effect on apparent cellular cholesterol efflux to HDL or lipid microemulsion, respectively. Overall cellular free cholesterol pool size was unaffected by the treatment, and probing by extracellular cholesterol oxidase did not detect gross change in the cellular surface cholesterol. This specific enrichment of cholesterol in the apoA-I-mediated cellular lipid efflux was reversed by protein kinase C inhibitors. Measurement of intracellular cholesterol esterification suggested that PMA induced translocation of intracellular cholesterol to a specific pool for apoA-I-mediated efflux, and a protein kinase C inhibitor reversed this effect.
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PMID:Independent regulation of cholesterol incorporation into free apolipoprotein-mediated cellular lipid efflux in rat vascular smooth muscle cells. 759 27

The aim of this study was to elucidate signal transduction pathways following high-density lipoprotein 3 (HDL3) fixation to HDL high-affinity binding sites and leading to translocation of newly synthesized cholesterol to the plasma membrane pool for efflux. First, membrane phosphatidylcholine (PC) breakdown and 1,2-diacylglycerol (DAG) production were investigated following HDL3 or tetranitromethane (TNM)-HDL incubation with smooth muscle cells in culture. Second, newly synthesized cholesterol was labeled using [3H] mevalonolactone. Phospholipase C (PLC) and protein kinase C (PKC) were stimulated using carbachol and phorbol 12-myristate 13-acetate. Translocation and efflux of newly synthesized cholesterol were monitored using the cholesterol oxidase method and TNM-HDL as cholesterol acceptor. Results showed that: (1) native HDL3 but not modified HDL was able to stimulate PC breakdown and DAG formation; and (2) PLC and PKC stimulation using specific agents induce cholesterol translocation from intracellular to plasma membrane pool. Taken together, these two sets of results suggest that native HDL3 could induce cholesterol translocation by a PLC/PKC process in smooth muscle cells.
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PMID:High-density lipoprotein 3 stimulates phosphatidylcholine breakdown and sterol translocation in rat aortic smooth muscle cells by a phospholipase C/protein kinase C-dependent process. 791 66