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 mechanism by which pertussis toxin (Ptx) causes lung edema is not clear. We investigated the role of pulmonary manganese superoxide dismutase (MnSOD) and protein kinase C (PKC) in Ptx-induced lung edema. We demonstrated that intraperitoneal injection of Ptx at a concentration of 5 microg/100 g body weight caused a similar degree of lung edema in 2 d, as measured by lung wet weight/dry weight ratio, in heterozygous MnSOD gene (Sod2)-knockout mice (Sod2(+/-)) and in their wild-type littermates (Sod2(+/+)). The level of lung MnSOD activity in Sod2(+/-) mice was approximately half that of Sod2(+/-) mice. Ptx had no effect on levels of lung MnSOD messenger RNA, immunoreactive protein, or enzyme activity in either Sod2(+/+) or Sod2(+/-) mice. Ptx also had no effect on lung copper-zinc SOD, catalase, and glutathione peroxidase activities in these mice. On the other hand, Ptx caused the activation of lung PKC, for example, by translocation of a 72-kD PKC isoform from the cytosolic fraction to the membrane fraction. Pretreatment of mice with bisindolylmaleimide, a PKC inhibitor, prevented both the Ptx-induced activation of PKC and lung edema. These data suggest that Ptx-induced lung edema in mice is, at least in part, due to the activation of lung PKC.
 ...
PMID:Pertussis toxin-induced lung edema. Role of manganese superoxide dismutase and protein kinase C. 1003 Aug 45

Cis-unsaturated fatty acids (c-UFAs) have been shown to be capable of decreasing the survival of macrophage tumor (AK-5) cells in vitro. This cytotoxic action of c-UFAs was found to be associated with an increase in free radical generation and lipid peroxidation process and a simultaneous decrease in cellular anti-oxidants such as superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione reductase, glutathione and vitamin E. In the present study, it was observed that c-UFAs such as gamma linolenic acid (GLA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can activate phospholipase C (PLC) and enhance diacylglycerol formation; all the fatty acids except alpha linolenic acid (ALA) increased the binding of phorbol dibutyrate acetate (PDBu) suggesting translocation of protein kinase C (PKC) and at the same time these fatty acids (especially GLA, AA, EPA and DHA) also enhanced PKC activity. AA, EPA and DHA decreased the activity of protein kinase A (PKA) both in the cytosol and particulate fractions whereas ALA and GLA enhanced the PKA activity in the particulate fractions; all the fatty acids except ALA reduced cyclic AMP levels and an enhanced phosphorylation of about 13 proteins of the nuclear fraction and about eight proteins of the plasma membrane fraction was noted in c-UFA treated AK-5 cells in vitro. These results suggest that c-UFAs can alter the activities of second messenger systems such as diacylglycerol and protein kinases and can phosphorylate both plasma membrane and nuclear proteins which are likely to be components of NADPH oxidase. Based on these results, it is suggested that fatty acids may mediate their cytotoxic action in part by modulating the expression of PKC. Activated PKC may then intensify the pro-oxidant state by augmenting NADPH oxidase, so inducing superoxide anion generation which may ultimately lead to cytolysis.
 ...
PMID:Effect of cis-unsaturated fatty acids on the activity of protein kinases and protein phosphorylation in macrophage tumor (AK-5) cells in vitro. 1031 18

We investigated the effects of alpha-tocopherol on diethylnitrosamine (DEN) initiation-phenobarbital (PB) promotion of hepatic foci in female Sprague-Dawley rats. Groups of eight rats were initiated with DEN (15 mg/kg) at 24 hours of age. After weaning, they received diets containing 500 ppm PB and various concentrations of alpha-tocopherol, deficient (0 ppm), adequate (100 ppm), and supplemented (5,000 ppm), for 24 weeks. Rats fed alpha-tocopherol-supplemented diets had significantly greater hepatic alpha-tocopherol levels than those fed alpha-tocopherol-deficient or -adequate diets (p < 0.05). Liver lipid peroxidation (measured as thiobarbituric acid-reactive substances) was significantly greater in rats fed alpha-tocopherol-deficient diets than in those fed alpha-tocopherol-adequate or -supplemented diets (p < 0.05). The dietary alpha-tocopherol level had no significant effect on the ratios of reduced glutathione (GSH) to oxidized GSH or reduced GSH to total GSH in the liver or on the plasma prostaglandin E2 concentration or on the activities of hepatic cytosolic and particulate protein kinase C. Rats fed alpha-tocopherol-adequate or -supplemented diets had significantly greater hepatic glutathione S-transferase, GSH reductase, and GSH peroxidase activities than those fed alpha-tocopherol-deficient diets (p < 0.05). The dietary alpha-tocopherol level did not significantly affect the formation of hepatic gamma-glutamyl transpeptidase- and placental glutathione S-transferase-positive foci. These results suggest that alpha-tocopherol does not influence hepatic foci formation and that reactive oxygen species may not be the underlying mechanism of hepatic foci formation in this DEN initiation-PB promotion model of hepatocarcinogenesis.
 ...
PMID:Lack of effect of dietary alpha-tocopherol on chemically induced hepatocarcinogenesis in rats. 1057 87

Although superoxide can directly quench endothelium-generated nitric oxide (NO), there is considerable evidence that oxidants derived from superoxide--notably peroxides and their further derivatives--can also impair NO bioactivity. In part, this reflects inhibition of NO synthase activity, perhaps mediated by the oxidation of labile sulfhydryl groups, as well as the activation of protein kinase C. Selenium deficiency exacerbates these effects, presumably owing to the crucial role of selenium-dependent thioredoxin reductase and glutathione peroxidases in preventing and reversing oxidant damage to proteins. High-normal homocyst(e)ine levels may induce an 'effective selenium deficiency' by suppressing glutathione peroxidase transcription in endothelial cells. Considerable epidemiology, primarily of European origin, points to mediocre selenium nutrition as a significant vascular risk factor; the risk associated with elevated plasma homocyst(e)ine levels is now well established. In addition to preventing LDL oxidation, vitamin E can be expected to minimize the contribution of lipid peroxides to endothelial dysfunction. Lipoic acid, which can function in vivo as a versatile antioxidant and sulfhydryl reductant, may have particular value for protecting endothelium from oxidants; its clinical utility in diabetic neuropathy may reflect this benefit. Good selenium status, as well as supra-nutritional intakes of lipoic acid, may down-regulate cytokine-mediated endothelial activation by helping to maintain the proper structure of oxidant-labile proteins--such as tyrosine phosphatases--that modulate this signaling. It can be concluded that a number of supplemental nutrients--including selenium, vitamin E, lipoic acid, and the vitamins that promote catabolism of homocysteine--have the potential to promote vascular health by mitigating the adverse impact of superoxide-derived oxidants on endothelial function.
 ...
PMID:Oxidants downstream from superoxide inhibit nitric oxide production by vascular endothelium--a key role for selenium-dependent enzymes in vascular health. 1060 66

Experimental diabetes promotes changes in biochemical activities of peripheral nervous tissue. Glutathione peroxidase activity decreases in sciatic nerve of diabetic mice very early after onset of experimental diabetes. Effective glycemic control with insulin restores the early lost glutathione peroxidase activity in peripheral nerve of diabetic mice to control values. Data are also presented demonstrating that glutathione peroxidase activity in diabetic mouse peripheral nerve is not modified by the constant delivery of calphostin C, a protein kinase C inhibitor, therefore this decrease seems to be independent on a protein kinase C mediated mechanism. Thus, the early glutathione peroxidase activity decrease in peripheral nerve of diabetic mice is closely related to hyperglycemia, and a tight glycemic control is rather effective in restoring the control levels of this enzymatic activity. The results herein do not rule out the benefits of antioxidant adjuvant therapies in diabetes to help recover the overall decrease in antioxidant defense in peripheral nerve elicited by the decrease of glutathione peroxidase activity.
 ...
PMID:Glycemic control and not protein kinase C inhibition prevents the early decrease of glutathione peroxidase activity in peripheral nerve of diabetic mice. 1064 94

Stroke occurs due to haemorrhage or occlusive injury and results in ischaemia and reperfusion injury. A variety of destructive mechanisms are involved including oxygen radical generation, calcium overload, cytotoxicity and apoptosis as well as the generation of inflammatory mediators. Ebselen, 2-phenyl-1, 2-benzisoselenazol-3(2H)-one (PZ 51, DR3305), is a mimic of GSH peroxidase which also reacts with peroxynitrite and can inhibit enzymes such as lipoxygenases, NO synthases, NADPH oxidase, protein kinase C and H(+)/K(+)-ATPase. Ebselen is in a late stage of development for the treatment of stroke. The molecular actions of ebselen contribute to its anti-inflammatory and anti-oxidant properties, which have been demonstrated in a variety of in vivo models. Numerous in vitro experiments using isolated LDL, liposomes, microsomes, isolated cells and organs have established that ebselen protects against oxidative challenge. Unlike many inorganic and aliphatic selenium compounds, ebselen has low toxicity as metabolism of the compound does not liberate the selenium moiety, which remains within the ring structure. Subsequent metabolism involves methylation, glucuronidation and hydroxylation. Experimental studies in rats and dogs have revealed that ebselen is able to inhibit both vasospasm and tissue damage in stroke models, which correlates with its inhibitory effects on oxidative processes. Results from randomised, placebo-controlled, double-blind clinical studies on the neurological consequences of acute ischaemic stroke, subarachnoid haemorrhage and acute middle cerebral artery occlusion, have revealed that ebselen significantly enhances outcome in patients who have experienced occlusive cerebral ischaemia of limited duration. The benefit achieved with ebselen is closely related to the rapidity with which the treatment is initiated, following the onset of the stroke attack. Safety and tolerability are good and no adverse effects have become apparent. Ebselen is currently at the pre-registration stage for subarachnoid haemorrhage and stroke in Japan.
 ...
PMID:Ebselen: prospective therapy for cerebral ischaemia. 1106 Jun 99

Prostaglandin (PG) F(2)a is known to initiate luteal cell apoptosis in the bovine corpus luteum (CL) via its specific receptor (FP) on the luteal membrane by inducing intracellular Ca(2+) mobilization and the activation of PKC. In order to identify the signaling components involved in cell apoptosis, mRNA levels and activities of antioxidative enzymes were analyzed using bovine CL at different stages of the estrous cycle. Northern blot analysis revealed that the levels of two isozymes of superoxide dismutase (SOD), the Mn and Cu/Zn types, and catalase are highly enriched in the middle estrous phase, whereas glutathione peroxidase (GPx) levels gradually decrease as the estrous cycle progresses. The incubation of bovine luteal cells with H(2)O(2) and mercaptosuccinate (MS), a specific inhibitor of GPx, resulted in an increase in chromatin DNA condensation and apoptotic DNA fragmentation. Analyses of the enzymatic activities of GPx and catalase support the RNA data, indicating that H(2)O(2) produced due to the lack of GPx is a potent inducer of luteal cell apoptosis.
 ...
PMID:The down-regulation of glutathione peroxidase causes bovine luteal cell apoptosis during structural luteolysis. 1138 9

In this study we show that SV-IV, a major immunomodulatory, anti-inflammatory, and sperm immunoprotective protein secreted from the rat seminal vesicle epithelium, acts in vitro as a substrate of protein kinase C (PKC) competing efficiently with H1 histone, a very well known PKC substrate. Electrospray mass spectrometry (ES-MS) analysis demonstrated that approximately 10% of the native SV-IV molecules were phosphorylated by PKC and that such a modification involved only a single serine residue (Ser58) out of the 22 occurring in the protein. Interestingly, this modification produced a substantial enhancement (approximately 50%) of the native SV-IV's ability to stimulate the activity of both horseradish peroxidase (POD) and selenium-dependent glutathione peroxidase (GPX), an enzyme that is known to protect the mammalian spermatozoa from oxidative stress and loss of motility in the female genital tract following ejaculation. In contrast, the phosphorylation of SV-IV on Ser58 did not produce any effect on the anti-inflammatory properties of SV-IV, as measured by its ability to inhibit the phospholipase A2.
 ...
PMID:Phosphorylation of seminal vesicle protein IV on Ser58 enhances its peroxidase-stimulating activity. 1143 54

Oxygen radicals and protein kinase C (PKC) mediate ischemic preconditioning. Using a cultured chick embryonic cardiomyocyte model of hypoxia and reoxygenation, we found that the oxygen radicals generated by ischemic preconditioning were H(2)O(2). Like preconditioning, H(2)O(2) selectively activated the epsilon-isoform of PKC in the particulate compartment and increased cell viability after 1 h of hypoxia and 3 h of reoxygenation. The glutathione peroxidase ebselen (converting H(2)O(2) to H(2)O) and the superoxide dismutase inhibitor diethyldithiocarbamic acid abolished the increased H(2)O(2) and the protection of preconditioning. PKC activation with phorbol 12-myristate 13-acetate increased cell survival; the protection of preconditioning was blocked by epsilonV(1-2), a selective PKC-epsilon antagonist. Similar to preconditioning, the protection of PKC activation was abolished by mitochondrial K(ATP) channel blockade with 5-hydroxydecanoate or by GABA receptor stimulation with midazolam or diazepam. In addition, PKC, mitochondrial ATP-sensitive K(+) (K(ATP)) channels, and GABA receptors had no effects on H(2)O(2) generated by ischemic preconditioning before prolonged hypoxia and reoxygenation. We conclude that H(2)O(2) opens mitochondrial K(ATP) channels and inhibits GABA receptors via activating PKC-epsilon. Through this signal transduction, preconditioning protects ischemic cardiomyocytes.
 ...
PMID:H(2)O(2) opens mitochondrial K(ATP) channels and inhibits GABA receptors via protein kinase C-epsilon in cardiomyocytes. 1189 76

Reactive oxygen species produced by neutrophils contribute to the pathogenesis of focal cerebral ischemia/reperfusion injury and signal the inflammatory response. We have previously shown that honokiol, an active principle extracted from Magnolia officinalis, has a protective effect against focal cerebral ischemia/reperfusion injury in rats that paralleled a reduction in reactive oxygen species production by neutrophils. To elucidate the underlying mechanism(s) of the antioxidative effect of honokiol, peripheral neutrophils isolated from rats were activated with phorbol-12-myristate-13-acetate (PMA) or N-formyl-methionyl-leucyl-phenylalanine (fMLP) in the presence or absence of honokiol. In this study, we found that honokiol inhibited PMA- or fMLP-induced reactive oxygen species production by neutrophils by three distinct mechanisms: (1) honokiol diminished the activity of assembled-NADPH oxidase, a major reactive oxygen species producing enzyme in neutrophils by 40% without interfering with its protein kinase C (PKC)-dependent assembly; (2) two other important enzymes for reactive oxygen species generation in neutrophils, i.e., myeloperoxidase and cyclooxygenase, were also inhibited by honokiol by 20% and 70%, respectively; and (3) honokiol enhanced glutathione (GSH) peroxidase activity by 30%, an enzyme that triggers the metabolism of hydrogen peroxide (H2O2). These data suggested that honokiol, acting as a potent reactive oxygen species inhibitor/scavenger, could achieve its focal cerebral ischemia/reperfusion injury protective effect by modulating enzyme systems related to reactive oxygen species production or metabolism, including NADPH oxidase, myeloperoxidase, cyclooxygenase, and GSH peroxidase in neutrophils.
 ...
PMID:The anti-inflammatory effect of honokiol on neutrophils: mechanisms in the inhibition of reactive oxygen species production. 1295 55


<< Previous 1 2 3 4 5 6 7 8 Next >>