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)

Vitamin E had an enhancing effect on active oxygen generation in concanavalin A (Con A)-stimulated alveolar macrophages (AMs) of rats. An inhibitor against protein kinase C (PKC) 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) suppressed a large part of this vitamin E-related effect, but a calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) did not inhibit the increase of active oxygen formation by vitamin E treatment. These results suggest that the activation of PKC presumably relates to the enhancing effect of vitamin E on active oxygen formation in Con A-stimulated AMs.
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PMID:A mechanism of vitamin E-enhanced active oxygen formation in concanavalin A-stimulated alveolar macrophage. 827 16

RRR-alpha-tocopheryl succinate (vitamin E succinate) was studied for its effects on interleukin-2 (IL-2) production by chicken splenic derived T lymphocytes and murine EL-4 thymic lymphoma cells. Supernatants from 0.1 microgram/mL vitamin E succinate-supplemented chicken splenic T cell cultures exhibited 42-72% enhanced IL-2 production over vehicle controls when tested in a chicken T cell blast bioassay. Supplementation of chicken splenic T lymphocyte cultures with butylated hydroxyanisole (BHT) and butylated hydroxytoluene (BHA) also induced elevated levels of IL-2, suggesting a role for antioxidants in IL-2 production by avian splenic T lymphocytes. Supernatants from vitamin E succinate-supplemented murine EL-4 cells (0.1 microgram/mL vitamin E succinate) induced 52-75% increased levels of IL-2 when compared to supernatants from vehicle controls when tested using a murine, IL-2-dependent CTLL-2 bioassay. IL-2 production by EL-4 cells was not enhanced by treatments with BHT, BHA, or Trolox, suggesting that vitamin E succinate-induced IL-2 production by EL-4 cells may involve a mechanism other than antioxidant effects. Vitamin E succinate plus suboptimal levels of the protein kinase C (PKC) activator phorbol myristate acetate (PMA) induced the highest levels of IL-2 by EL-4 cells. The studies provide evidence that vitamin E succinate can directly potentiate either the production or release of IL-2 from avian splenocytes and murine EL-4 cells.
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PMID:RRR-alpha-tocopheryl succinate induced interleukin-2 production by avian splenic T lymphocytes and murine EL-4 thymic lymphoma cells. 837 8

We have previously shown that oxidized low density lipoprotein (LDL) but not native LDL stimulated DNA synthesis in cultured smooth muscle cells (SMC) and that alpha-tocopherol (vitamin E) inhibited this proliferative response (Lafont, A., Chai, Y. C., Cornhill, J. F. , Whitlow, P. L., Howe, P. H., and Chisolm, G. M.(1995) J. Clin. Invest. 95, 1018-1025). The moiety of oxidized LDL that stimulates DNA synthesis and the cellular mechanism for this potentially mitogenic effect are not known. We now report that lipid fractions containing lysophospholipids from oxidized LDL or phospholipase A2-treated native LDL stimulated SMC DNA synthesis as did palmitoyl lysophosphatidylcholine (lysoPC). Protein kinase C inhibitors and down-regulation of protein kinase C activity by phorbol ester inhibited oxidized LDL- and lysoPC-induced DNA synthesis. A neutralizing monoclonal antibody against fibroblast growth factor-2 significantly inhibited oxidized LDL and lysoPC-induced DNA synthesis in SMC; irrelevant antibodies were ineffective. Vitamin E inhibited the DNA synthesis stimulated by lysoPC, an observation that distinguished this effect from DNA synthesis induced by another detergent, digitonin. These results suggest that oxidized LDL and its lysoPC moiety stimulate SMC to enter the cell cycle via an oxidative mechanism that causes the release of fibroblast growth factor-2 and a subsequent autocrine or paracrine response.
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PMID:Oxidized low density lipoprotein and lysophosphatidylcholine stimulate cell cycle entry in vascular smooth muscle cells. Evidence for release of fibroblast growth factor-2. 866

The cyclobutane pyrimidine dimer (CPD) photolyase in fish cells is known to be regulated by environmental factors, such as light, hydrogen peroxide and growth inhibition. The induction of CPD photolyase by light in cultured goldfish cells was dependent on the wavelength of the light, and UVA and blue light had high inductive activity. The spectrum for CPD photolyase activity was different from that for the induction. Treatment with blue or yellow light for a short time, which did not induce any CPD photolyase, induced high CPD photolyase activity in the presence of the photosensitizers, TPPS (monosulfonated meso-tetraphenyl porphine) and ALPS (aluminum phthalocyanine tetrasulfonate), respectively. These results suggest that the induction of CPD photolyase might be triggered by active oxygen produced by light and cellular photosensitizers. We also found that immediately after treatment with UVA, blue light or a photosensitizer in combination with light, cellular attachment to the substratum was enhanced, as was the CPD photolyase activity. Pretreatment with a flavonoid, quercetin, inhibited both photoinduction of CPD photolyase and enhancement of cellular attachment. Vitamin E inhibited only photoinduction of CPD photolyase activity. Treatment with H7, a strong inhibitor for protein kinase C, after light treatment inhibited photoinduction of CPD photolyase activity, but an analogue of H7, Ha1004, which is a weak inhibitor of protein kinase C, did not have such an effect.
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PMID:Induction of cyclobutane pyrimidine dimer photolyase in cultured fish cells by UVA and blue light. 897 35

The preventive effect of vitamin E and Probucol against atherosclerosis in rabbits were compared. Atherosclerosis was induced by a 2% cholesterol-containing vitamin E-poor diet (5-10 ppm). Six groups of five rabbits each were studied. Group I (control) was fed on a vitamin E-poor diet. The other groups had the following supplements: group II, 50 mg/kg vitamin E i.m.; group III, 2% cholesterol; group IV, 2% cholesterol plus 50 mg/kg vitamin E i.m., group V, 2% cholesterol plus 1% Probucol; group VI, 2% cholesterol + 1% Probucol plus 50 mg/kg vitamin E i.m. After 4 weeks, aortas were removed and analyzed by light and scanning electron microscopy for atherosclerotic lesions. Samples of the media were analyzed for protein kinase C activity. The aortas of cholesterol-fed rabbits showed typical atherosclerotic lesions, detected by microscopic examination, their media smooth muscle cells exhibited an increase in protein kinase C activity. Vitamin E fully prevented cholesterol-induced atherosclerotic lesions and the induction of protein kinase C activity. Probucol was not effective in preventing either cholesterol-induced atherosclerotic lesions or the induction of protein kinase C activity. These results show that the protective effect of vitamin E against hypercholesterolemic atherosclerosis is not produced by an other antioxidant such as Probucol, and therefore, may not be linked to the antioxidant properties of this vitamin. The effects observed at the level of smooth muscle cells ex vivo suggest an involvement of signal transduction events in the protective effect of vitamin E against atherosclerosis.
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PMID:Effect of vitamin E and probucol on dietary cholesterol-induced atherosclerosis in rabbits. 943 96

Vitamin E (alpha-tocopherol), one of the most important natural antioxidants, is assumed to be beneficial in the prevention of cardiovascular diseases. alpha-Tocopherol exhibits acyl-peroxyl-radical scavenger properties and exerts cell-mediated actions in the hemovascular compartment, such as inhibition of superoxide anion (O-2) production by leukocytes. The aim of this study was to examine the mechanism underlying the inhibitory effect of alpha-tocopherol on O-2 production by human monocytes. In activated monocytes O-2 is produced by the NADPH-oxidase enzyme complex. The oxidase activation elicited by phorbol myristate acetate (PMA) requires membrane translocation of several cytosolic factors. We found that in human PMA-stimulated adherent monocytes, alpha-tocopherol (but not beta-tocopherol) inhibited O-2 production in intact cells but had no effect on a membrane preparation containing activated NADPH-oxidase, suggesting that alpha-tocopherol impairs the assembly process of the enzyme complex. We showed that translocation and phosphorylation of the cytosolic factor p47(phox) were reduced in monocytes preincubated with alpha-tocopherol. We verified that the tryptic phosphopeptide map of monocyte p47(phox) was similar to that of neutrophil p47(phox), indicating that several serine residues were phosphorylated. Peptides whose phosphorylation is dependent on protein kinase C (PKC) were phosphorylated to a lesser degree when p47(phox) was immunoprecipitated from alpha-tocopherol-treated monocytes. In vitro, the activity of PKC from monocytes was inhibited by alpha-tocopherol in a specific manner compared with that of beta-tocopherol or Trolox(R). Membrane translocation of PKC was not affected. These results show that alpha-tocopherol inhibits O-2 production by human adherent monocytes by impairing the assembly of the NADPH-oxidase and suggest that the inhibition of phosphorylation and translocation of the cytosolic factor p47(phox) results from a decrease in PKC activity.
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PMID:alpha-tocopherol inhibits the respiratory burst in human monocytes. Attenuation of p47(phox) membrane translocation and phosphorylation. 983 25

Insulin resistance of skeletal muscle is fundamental to both syndrome X and its frequent sequel, type II diabetes. In these disorders, excessive exposure of muscle to free fatty acids (FFAs) and their metabolic derivatives appears to play a prominent role in the induction of insulin resistance. Recent evidence suggests that activation of novel isoforms of protein kinase C (PKC) by diacylglycerol may mediate at least part of the adverse impact of FFAs on muscle insulin sensitivity. Vitamin E and fish oil omega-3s, by promoting the activity of diacylglycerol kinase and inhibiting that of phosphatidate phosphohydrolase, should reduce diacylglycerol levels, thus accounting for their documented favorable impact on insulin sensitivity. Thiazolidinediones such as troglitazone, on the other hand, appear to intervene in the signaling pathway whereby PKC down-regulates insulin function. The insulin-sensitizing activity of chromium picolinate may be attributable, at least in part, to increased expression of insulin receptors. In combination with lifestyle modifications which reduce FFA exposure--weight loss, very-low-fat eating, excessive training--these measures can be expected to work in a complementary way to promote increased numbers of insulin receptors that are more functionally competent. As these measures appear to be safe and well-tolerated, they may have utility for the prevention of diabetes as well as its therapy. When they do not prove sufficient to achieve optimal glycemic control, excessive hepatic glucose output and impaired cell response to glucose can be addressed with metformin and sulfonylureas, respectively. The prospects for a rational medical management of type II diabetes, obviating the need for injectible insulin, have never been brighter.
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PMID:Complementary measures for promoting insulin sensitivity in skeletal muscle. 1005 64

Vitamin E has emerged as a major factor in the prevention and inhibition of cardiovascular disease. The inhibition of platelet function, especially adhesion, which is an important event in the development and propagation of cardiovascular disease, plays a crucial role in the beneficial effect that vitamin E exerts on such diseases. Although it is best known for its antioxidant activity, vitamin E interferes with platelet adhesion via a mechanism that is independent of this action. Vitamin E-induced inhibition of protein kinase C leads to decreased platelet pseudopodia formation upon stimulation by agonists, a process that is instrumental in reducing platelet adhesion. In conjunction with potent inhibitors of platelet aggregation, vitamin E has become a widely applied treatment regimen for this group of diseases. Increased bleeding, especially when vitamin E is combined with a potent platelet aggregation inhibitor, has to be considered a side effect of its mechanism of action, but should not detract from the potential benefits for the majority of patients who take this vitamin.
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PMID:Vitamin E, a modifier of platelet function: rationale and use in cardiovascular and cerebrovascular disease. 1057 6

Vitamin E was originally considered a dietary factor of animal nutrition especially important for normal reproduction. The significance of vitamin E has been subsequently proven as a radical chain breaking antioxidant that can protect the integrity of tissues and play an important role in life processes. More recently alpha-tocopherol has been found to possess functions that are independent of its antioxidant/radical scavenging ability. Absorption in the body is alpha-tocopherol selective and other tocopherols are not absorbed or are absorbed to a lesser extent. Furthermore, pro-oxidant effects have been attributed to tocopherols as well as an anti-nitrating action. Non-antioxidant and non-pro-oxidant molecular mechanisms of tocopherols have been also described that are produced by alpha-tocopherol and not by beta-tocopherol. alpha-Tocopherol specific inhibitory effects have been seen on protein kinase C, on the growth of certain cells and on the transcription of some genes (CD36, and collagenase). Activation events have been seen on the protein phosphatase PP2A and on the expression of other genes (alpha-tropomyosin and Connective Tissue Growth Factor). Non-antioxidant molecular mechanisms have been also described for gamma-tocopherol, delta-tocopherol and tocotrienols.
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PMID:Vitamin E: non-antioxidant roles. 1079 17

The development of atherosclerosis is a multifactorial process in which both elevated plasma cholesterol levels and proliferation of smooth muscle cells play a central role. Numerous studies have suggested the involvement of oxidative processes in the pathogenesis of atherosclerosis and especially of oxidised low density lipoproteins. Some epidemiological studies have shown an association between high dietary intake or high serum concentrations of vitamin E and lower rates of ischemic heart disease. Recently, the Cambridge Heart Antioxidant Study (CHAOS) reported strong protection by high vitamin E doses against the risk of fatal and non fatal myocardial infarction. Here we have shown that incubation of vascular smooth muscle cells in the presence of alpha-tocopherol resulted in inhibition of cell proliferation and protein kinase C activity. Since beta-tocopherol and probucol are not inhibitory, the effect of alpha-tocopherol is considered due to a non-oxidant mechanism. In order to understand the protective role of alpha-tocopherol against atherosclerosis in vivo the following rabbit studies were carried out. Atherosclerosis was induced by a vitamin E poor diet containing 2% cholesterol in a group of rabbit. The other groups had 2% cholesterol in the diet plus 50 mg/kg vitamin E i.m. or 1% probucol or 50 mg/kg vitamin E plus 1% probucol. After 4 weeks, aortas were removed and analysed by microscopy for atherosclerotic lesions. Samples of the media were analysed for protein kinase C activity. The aortas of cholesterol-fed rabbits showed typical atherosclerotic lesions, detected by microscopic examination, their media smooth muscle cells exhibited an increase in protein kinase C activity. Vitamin E fully prevented cholesterol induced atherosclerotic lesions and the induction of protein kinase C activity while probucol was not effective. These results show that the protective effect of vitamin E against hypercholesterolemic atherosclerosis is not produced by an other antioxidant such as probucol and, therefore, may not be linked to the antioxidant properties of this vitamin. The effects observed at the level of smooth muscle cells in vitro and ex-vivo suggests an involvement of signal transduction events in the protective effect of vitamin E against atherosclerosis.
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PMID:Effect of vitamin E on the development of atherosclerosis. 1096 37


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