Hydroxyl radical involvement in the luminol chemiluminescence from the reaction of arachidonic acid with sheep vesicular gland microsomes

O’Brien, Peter J.; Hulett, Leslie G.

doi:10.1016/0090-6980(80)90167-7

Cited by 21 publications

(6 citation statements)

References 13 publications

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“…The cascade of PG biosynthesis constitutes a controlled radical process highly sensitive to the oxidative state Gale and Egan, 1984;Lands et al, 1984;Whorton et al, 1985). For example low doses of H202 produce rapid inhibition of cyclo-oxygenase activity, a key step in the biosynthesis of PGE2 (Whorton et al, 1985) and lipid peroxides inactivate PGI2 synthase (O'Brien and Hulett, 1980;Egan et al, 1984). It is therefore plausible that the changes in the metabolism of oxygen free radicals induced by the elevated CuZnSOD constitute the primary cause of the reduced synthesis and release of PGs in the cells and animals studied.…”

Section: Discussionmentioning

confidence: 99%

Gene dosage of CuZnSOD and Down's syndrome: diminished prostaglandin synthesis in human trisomy 21, transfected cells and transgenic mice.

1991

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Patients with Down's syndrome (DS) exhibit elevated activity of copper zinc superoxide dismutase (CuZnSOD) caused by the trisomy 21 state. To investigate the possible involvement of CuZnSOD gene dosage in perturbation of prostaglandin biosynthesis we analyzed transfected cells and transgenic mice that express elevated levels of human CuZnSOD. It was found that the synthesis of prostaglandin E2 (PGE2) was diminished in transfected PC12‐CuZnSOD cells as well as in fibroblasts from DS patients. Primary cells derived from transgenic CuZnSOD mice showed similar reduction. Impaired biosynthesis of prostaglandins was not confined to cells grown in culture since secretion of PGE2 and PGD2 by kidney and cerebellum of transgenic CuZnSOD was significantly lower than in non‐transgenic littermate mice. These findings strongly suggest that overexpression of the CuZnSOD gene induces a demotion in PGE2 and PGD2 formation and establish a connection between alteration of prostaglandin biosynthesis in trisomy 21 cells and gene dosage of CuZnSOD.

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Section: Discussionmentioning

confidence: 99%

Gene dosage of CuZnSOD and Down's syndrome: diminished prostaglandin synthesis in human trisomy 21, transfected cells and transgenic mice.

1991

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“…Enzymatic reduction of prostaglandin G2 to PGH2 by this peroxidase has been shown to produce a radical which is destructive towards cyclooxygenase activity (19). Although the identity of this radical remains controversial (37), the highly reactive OH' has been implicated (19,38). Production of OH' radicals may also be involved in the inactivation of cyclooxygenase by H202.…”

Section: Resultsmentioning

confidence: 99%

Effect of hydrogen peroxide on prostaglandin production and cellular integrity in cultured porcine aortic endothelial cells.

Whorton¹,

Montgomery²,

Kent³

1985

J. Clin. Invest.

156

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Oxidative damage to the vascular endothelium may play an important role in the pathogenesis of atherosclerosis and aging, and may account in part for reduced vascular prostacyclin (PGI2) synthesis associated with both conditions. Using H202 to induce injury, we investigated the effects of oxidative damage on PGI2 synthesis in cultured endothelial cells (EC). Preincubation of EC with H202 produced a dose-dependent inhibition (inhibitory concentration [ICso1 = 35 gM) of PGI2 formation from arachidonate. The maximum dose-related effect occurred within 1 min after exposure although appreciable H202 remained after 30 min (30% of original). In addition, H202 produced both a time-and dose-dependent injury leading to cell disruption, lactate dehydrogenase release, and 51Cr release from prelabeled cells. However, in dramatic contrast to H202 effects on PGI2 synthesis, loss of cellular integrity required doses in excess of 0.5 mM and incubation times in excess of 1 h. The superoxide-generating system, xanthine plus xanthine oxidase, produced a similar inhibition of PGI2 formation. Such inhibition was dependent on the generation of H202 but not superoxide in that catalase was completely protective whereas superoxide dismutase was not. H202 (50 gM) also effectively inhibited basal and ionophore A23187 (0.5 1M)-stimulated PGI2 formation. However, H202 had no effect on phospholipase A2 activity, because ionophore A23187-induced arachidonate release was unimpaired. To determine the effects on cyclooxygenase and PGI2 synthase, prostaglandin products from cells prelabeled with IHlarachidonate and stimulated with ionophore A23187, or products formed from exogenous arachidonate were examined. Inhibition of cyclooxygenase but not PGI2 synthase was observed. Incubation of H202-treated cells with prostaglandin cyclic endoperoxide indicated no inhibition of PGI2 synthase. Thus, in EC low doses of H202 potently inhibit cyclooxygenase after brief exposure whereas larger doses and prolonged exposure are required for classical cytolytic effects. Surprisingly, PGI2 synthase, which is known to be extremely sensitive to a variety of lipid peroxides, is not inhibited by H202. Lipid solubility, enzyme location within the EC mem-

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“…This chemiluminescence was ascribed to the cyclooxygenase reaction since it was inhibited by indomethacin. Similarly, O'Brien and Hulett (1980) found that luminol-dependent chemi-149 luminescence associated with the reaction between vesicular gland microsomes and arachidonic acid was also inhibited by SOD. It seems, however, that superoxide anion radical is not a direct product of the cyclooxygenase and hydroperoxidase reactions.…”

Section: Generation Of Superoxide Anion Radical From Arachidonate Metmentioning

confidence: 99%

Appearance of superoxide anion radical in cerebral extracellular space during increased prostaglandin synthesis in cats.

Kontos¹,

Wei²,

Ellis³

et al. 1985

Circulation Research

268

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SUMMARY. When increased prostaglandin synthesis was induced in anesthetized cats equipped with cranial windows by topical application of arachidonate (200 Mg/ml) or bradykinin (20 /xg/ ml), there was reduction of nitroblue terrazolium, resulting in deposition of the reduced insoluble form of this dye on the brain surface. The amount of reduced nitroblue terrazolium deposited on the brain surface was measured spectrophotometrically after fixation of the brain by perfusion with aldehydes to eliminate interference from hemoglobin. Topical application of 56 U/ml superoxide dismutase or 20 Mg/mJ indomethacin inhibited nitroblue terrazolium reduction by 76.5%-82.5% and by 78%-85.5%, respectively. These results show that most of the nitroblue terrazolium reduction was accounted for by superoxide anion radical generated in the course of arachidonate metabolism via the cyclooxygenase pathway. No superoxide production could be detected in the absence of arachidonate or bradykinin. Histological examination showed no evidence of parenchymal cellular damage or vascular damage and no accumulation of leukocytes. Pronounced leukocyte accumulation occurred 24 hours after topical arachidonate in rabbits with chronically implanted cranial windows. Superoxide appearance was reduced severely by 4,4'-diisothiocyano-2,2'-stilbene disulfonate and phenylglyoxal, two specific inhibitors of the anion channel. The most likely explanation for these findings is that increased metabolism of exogenous or endogenous arachidonate via cyclooxygenase results in the appearance of superoxide anion radical in cerebral extracellular space. Superoxide crosses the membrane of undamaged cells via the anion channel. (Circ Res 57:142-151, 1985)

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Hydroxyl radical involvement in the luminol chemiluminescence from the reaction of arachidonic acid with sheep vesicular gland microsomes

Cited by 21 publications

References 13 publications

Gene dosage of CuZnSOD and Down's syndrome: diminished prostaglandin synthesis in human trisomy 21, transfected cells and transgenic mice.

Gene dosage of CuZnSOD and Down's syndrome: diminished prostaglandin synthesis in human trisomy 21, transfected cells and transgenic mice.

Effect of hydrogen peroxide on prostaglandin production and cellular integrity in cultured porcine aortic endothelial cells.

Appearance of superoxide anion radical in cerebral extracellular space during increased prostaglandin synthesis in cats.

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