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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polyunsaturated fatty acids (PUFA) are vulnerable to peroxidative attack. Protecting PUFA from peroxidation is essential to utilize their beneficial effects in health and in preventing disease. The antioxidants vitamin E, t-butylhydroxy toluene (BHT) and t-butylhydroxy anisole (BHA) inhibited ascorbate/Fe(2+)-induced lipid peroxidation in rat liver microsomes. In addition, a number of spice principles, for example, curcumin (5-50 microM) from turmeric, eugenol (25-150 microM) from cloves and capsaicin (25-150 microM) from red chillies inhibited lipid peroxidation in a dose-dependent manner. Zingerone from ginger inhibited lipid peroxidation at high concentrations (greater than 150 microM) whereas linalool (coriander), piperine (black pepper) and cuminaldehyde (cumin) had only marginal inhibitory effects even at high concentrations (600 microM). The inhibition of lipid peroxidation by curcumin and eugenol was reversed by adding high concentrations of Fe2+.
Mol Cell Biochem 1992 Apr
PMID:Studies on spice principles as antioxidants in the inhibition of lipid peroxidation of rat liver microsomes. 158 34

The disposition of vitamin E was examined in cultured rat hepatocytes intoxicated with tert-butyl hydroperoxide (TBHP). Culturing of the cells overnight (18-20 hr) with approximately 60 nM alpha-tocopherol (alpha-T) equivalents [Williams' E medium, 18 nM tocopherol phosphate (alpha-TP), 9% fetal calf serum, 43 nM alpha-T] resulted in a content of alpha-T that was 16% of the concentration of vitamin E measured in freshly isolated hepatocytes. Supplementation of the medium with 1 microM alpha-TP maintained the alpha-T concentration of the cultured cells at the level of freshly isolated hepatocytes. Supplemented hepatocytes exposed to TBHP showed decreased lipid peroxidation and delayed cell killing, compared with hepatocytes not cultured overnight with alpha-TP. Killing of the supplemented cells by TBHP was accompanied by a loss of alpha-T. Pretreatment of supplemented hepatocytes with the iron chelator deferoxamine prevented much of the loss of alpha-T. At the same time, deferoxamine inhibited both the lipid peroxidation and cell killing. The antioxidant N,N'-diphenyl-1,4-phenylenediamine reduced the loss of alpha-T and significantly decreased lipid peroxidation. In the presence of N,N'-diphenyl-1,4-phenylenediamine, cell killing was delayed by 15 min and reduced in extent. Overnight supplementation of hepatocytes with nonesterified alpha-T, or vitamin E esters other than alpha-TP, similarly rendered the cells less sensitive to TBHP. The nonesterified alpha-T produced a higher cell-associated vitamin E concentration than did the esters; however, nonesterified alpha-T did not result in greater protection against TBHP. These data indicate that the mechanisms of the cell killing by TBHP are the same in cultured hepatocytes that contain low or physiological concentrations of vitamin E.
Mol Pharmacol 1992 Jun
PMID:Effects of vitamin E on the killing of cultured hepatocytes by tert-butyl hydroperoxide. 161 14

Human brain levels of glutathione (GSH), glutathione disulfide (GSSG), and vitamin E were measured in neurologically normal control patients and two groups of patients with neurodegeneration: those with Alzheimer's disease (AD), and AD with some features of Parkinson's disease (AD-PD). Control brain samples contained GSH levels more than 50 times higher than GSSG. The levels of GSH were highest in the caudate nucleus and lowest in the medulla. In patients with AD or AD-PD, hippocampal levels of GSH were significantly higher than controls. Patients with AD also demonstrated high GSH levels in the midbrain compared to normal. In contrast, patients with AD-PD did not have significantly elevated GSH levels in this site. GSSG levels were not significantly different in any brain region between controls and diseased patients. In control brains, the medulla had higher levels of vitamin E than any other brain region. The caudate nucleus had the lowest levels, which were about half the levels in the medulla. Control levels of vitamin E in the midbrain were about 18.8 micrograms/g. In AD patients the midbrain levels of vitamin E doubled to 42.3 micrograms/g. This doubling also occurred in AD-PD patients where midbrain vitamin E levels increased to 44.0 micrograms/g. These results may indicate that compensatory increases in GSH and vitamin E levels occur following damage to specific brain regions in patients with AD or AD-PD.
Mol Chem Neuropathol 1991 Jun
PMID:Alzheimer's and Parkinson's disease. Brain levels of glutathione, glutathione disulfide, and vitamin E. 195 64

Oxidative stress induced by cumene hydroperoxide was studied in cultured neonatal rat myocytes. A progressive increase of irreversible cell injury as determined by leakage of the cytoplastic enzyme alpha-hydroxybutyrate dehydrogenase (alpha-HBDH) from the cells was noted at concentrations ranging from 25-100 microM cumene hydroperoxide (incubation time 90 min). Cumene hydroperoxide-induced damage was reduced or prevented by several compounds: the application of Trolox C, a water-soluble vitamin E analogue, and of phospholipase A2 inhibitors chlorpromazine and (to a lesser extent) quinacrine prevented alpha-HBDH release. ICRF-159, a chelator of divalent cations, ascorbic acid, a potent antioxidant, and the cysteine protease inhibitor leupeptin did not reduce the cumene hydroperoxide-induced cytotoxicity. Detoxification of hydroperoxides by the glutathione peroxidase system results in an increased flux through the pentose phosphate shunt and loss of NADPH. Glucose inhibited the cumene hydroperoxide-induced alpha-HBDH release, probably by replenishing NADPH. These results indicate that cumene hydroperoxide, after exhaustion of the glutathione system, induces irreversible injury in cultured myocytes by a mechanism that depends to a large extent on deterioration of cellular membranes caused by lipid peroxidation and phospholipase activation.
J Mol Cell Cardiol 1990 Oct
PMID:Prevention of cumene hydroperoxide induced oxidative stress in cultured neonatal rat myocytes by scavengers and enzyme inhibitors. 209 37

Peroxidation of myocardial-membrane phospholipid is considered an important pathogenic component of heart muscle damage in ischemia and reperfusion. The extent to which membrane alpha-tocopherol (vitamin E) in the heart can modulate such damage and protect against it is a matter of controversy. The relative alpha-tocopherol deficit of spontaneously-hypertensive (SH) rat myocardium as compared to the myocardium of the Wistar-Kyoto (W/K) normotensive parent strain prompted use of these animals to identify and characterize any protective antiperoxidant role of endogenous, myocardial-membrane alpha-tocopherol. With exposure to a superoxide- and iron-containing initiator of peroxidation, the membrane complements from the ventricular myocardia of the SH rat and the W/K parent strain were found to have very different peroxidative-injury profiles. SH-rat myocardial membrane demonstrated a marked sensitivity to peroxidation as reflected in the acute onset and rapid progression of phospholipid damage. The greater susceptibility of SH-rat myocardial membrane to free-radical attack could not be explained by inter-strain compositional differences in membrane polyunsaturated fatty acids or fatty aldehydes. Rather, the basis for the enhanced peroxidation was identified as the 3-fold lower alpha-tocopherol content of SH-rat myocardial membrane with respect to the heart-muscle membrane from the normotensive animal. The relative alpha-tocopherol deficit not only increased the susceptibility of SH-rat cardiac membrane to damage under pro-oxidant conditions, but also reduced the efficacy of exogenously supplied antioxidant intervention. These findings demonstrate that membrane alpha-tocopherol tone is a critical protectant of myocardial phospholipid against oxidative injury and acts as a determinant of the course of heart-membrane peroxidative damage.
J Mol Cell Cardiol 1989 Nov
PMID:Oxidative injury to myocardial membrane: direct modulation by endogenous alpha-tocopherol. 255 23

The cardiotoxic effect of the beta-adrenergic agonist isoproterenol was studied in cultured neonatal rat myocytes. A progressive increase in irreversible cell injury as determined by leakage of the cytoplasmic enzyme alpha-hydroxybutyrate dehydrogenase (alpha-HBDH) from the cells was noted at concentrations above 2.5 x 10(-4) M isoproterenol (exposure time 6 h). The isoproterenol-induced cell damage was reduced or prevented by several free radical scavengers: the application of Trolox C, a water-soluble vitamin E analogue, ICRF-159, a chelator of divalent cations, ascorbic acid, a potent antioxidant, as well as the enzymatic free radical scavengers superoxide dismutase and catalase reduced alpha-HBDH release. This study corroborates the hypothesis that oxidation products of isoproterenol, especially the formation of oxygen- and/or oxygen-derived free radicals, are responsible for the cytotoxicity observed after prolonged exposure to isoproterenol. In contrast to isoproterenol, exposure to 5 x 10(-4) M fenoterol, another beta-adrenergic agonist which is not oxidized, does not impair the viability of the myocytes. Moreover, application of the beta-blocker propranolol (10(-4) M, 10(-5)M) in combination with 5 x 10(-4) M isoproterenol does not prevent alpha-HBDH release. These findings suggest that isoproterenol-induced cardiotoxicity is not the result of excessive beta-adrenoceptor activation, but is mediated by the formation of free radicals.
J Mol Cell Cardiol 1989 Dec
PMID:Isoproterenol-induced cytotoxicity in neonatal rat heart cell cultures is mediated by free radical formation. 263 11

Although muscle and nerve are reasonably well protected against active oxygen and related free radicals, environmental or inherited malfunctions can overpower their defences. Active oxygen is involved in many neuropathies and myopathies. In every case the damage is caused by agents which exert effects disproportionately greater than the quantities encountered, through a variety of amplification mechanisms. We can categorize these amplification mechanisms as follows: (a) non-replacement of targets (e.g. loss of genetic information, ataxia telangectasia being an hereditary ataxia in which an oxygen mediated chromosomal instability is apparent), (b) non-removal of unwanted materials (e.g. lipofuscin accumulation in brain and heart), (c) redox cycling, usually involving catalysis by trace-metal ions (e.g. some forms of Parkinsonism), (d) non-redox catalysis (e.g. toxicity in cardiac muscle or brain due to vanadium or aluminium respectively), (e) modification of ion transport (e.g. calcium ionophore or acrylamide induce histopathological changes in muscle, similar in some respects to those seen in Duchenne muscular dystrophy), (f) compromised defences (e.g. muscle and nerve become particularly susceptible to free radical damage after loss of the protective actions of vitamin E), and (g) amplification by inflammatory and immune responses (e.g. multiple sclerosis, reperfusion injury to brain and heart, and traumatic injury to nervous tissue). Unfortunately, a variety of therapeutic agents which might be expected to protect against almost every conceivable form of oxygen mediated damage have proved clinically ineffective in most of these disorders. The reasons for this will be explored with an emphasis on common features, differences, mechanisms, and potential therapeutic approaches.
Mol Cell Biochem 1988 Dec
PMID:Active oxygen in neuromuscular disorders. 306 22

Free radicals have been suggested to play a role in adriamycin-induced cardiomyopathy. Adriamycin-induced myocardial effects were examined in rats maintained on a vitamin E deficient diet. Animals were divided into four groups: I, control; II, adriamycin-treated; III, vitamin E deficient diet; IV, vitamin E deficient diet plus adriamycin treatment. Adriamycin-treated animals (groups II and IV) were given six injections (i.p.) over two weeks for producing a cumulative dose of 15 mg/kg. Animals in groups III and IV were placed on vitamin E deficient diet starting two weeks prior to the first injection of adriamycin or vehicle. Myocardial tissue analysis were performed on animals sacrificed 1 week after the last injection. Mortality was significantly higher in group IV which also showed doubling of myocardial malondialdehyde content relative to the non-adriamycin-treated vitamin E deficient group (III). Myocardial cell damage in group IV was characterized by separation of the external lamina, subsarcolemmal changes, mitochondrial swelling and myofibril dropout. Group II hearts showed only a mild dilation of the sarcotubules and swelling of the mitochondria. Total sialic acid content of the sarcolemma in groups II, III and IV was 55, 90 and 24% of the control values in group I. These data show a characteristic sarcolemmal injury produced by adriamycin in hearts of animals with reduced antioxidant capacity which is probably mediated by increased free radical activity as well as lipid peroxidation.
Mol Cell Biochem 1988 Dec
PMID:Vitamin E deficiency accentuates adriamycin-induced cardiomyopathy and cell surface changes. 323 Dec 21

Eosinophilic enteritis and eosinophilia, in addition to muscular dystrophy and occasionally liver necrosis, were experimentally induced in male Sprague-Dawley rats with a vitamin E- and selenium-deficient diet (basal diet) for 9 weeks. Cecum and ileum were affected more frequently and severely than other segments of the gastrointestinal tract. Eosinophils were multifocally or diffusely distributed in the intestinal wall but were most severe in the muscular layer and in the submucosa. Eosinophils were also present in stomach, liver with massive hepatocellular necrosis, and skeletal muscle with marked myonecrosis. Eosinophilic enteritis and eosinophilia were not observed in rats fed the basal diet supplemented with either vitamin E (100 or 200 ppm) or selenium (0.1 or 1.0 ppm). Eosinophilic enteritis, eosinophilia, and muscular dystrophy regressed when vitamin E- and selenium-deficient rats were subsequently fed either the vitamin E- or selenium-supplemented diet for 4-5 weeks. These findings suggest that vitamin E and selenium deficiency may play a role in the development of a diffuse type of eosinophilic enteritis and eosinophilia.
Exp Mol Pathol 1988 Apr
PMID:Induction of eosinophilic enteritis and eosinophilia in rats by vitamin E and selenium deficiency. 335 Jan 41

A critical review of the literature on the effects of vitamin E and selenium deficiences on unsaturated fatty acid metabolism reveals that some of these effects are inconsistent with the antioxidant hypothesis of these nutrients as their only biological function. On the basis of these data it is proposed that vitamin E and selenium play a role in the desaturation of n-3 and n-6 polyunsaturated fatty acids by participating in the microsomal electron transport chain and in a proposed peroxidase moiety of the desaturase complex, respectively. A re-interpretation of the experimental literature in terms of the proposed hypothesis is provided, with some suggestions to test its main tenets.
Mol Cell Biochem 1986 Feb
PMID:Vitamin E and selenium participation in fatty acid desaturation. A proposal for an enzymatic function of these nutrients. 351 61


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