Prostaglandin biosynthesis can be triggered by lipid peroxides

Hemler, Martin E.; Cook, Harold W.; Lands, William E.M.

doi:10.1016/0003-9861(79)90038-9

Cited by 335 publications

(71 citation statements)

References 24 publications

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“…The inhibition of the AIsc response to X/XO by CAT, coupled with reproduction of the X/XO response with G/GO and exogenous H202, provide strong evidence that H202 is the active species altering transport. The possibility that 0H, formed from H202 by the Haber-Weiss (26)(27)(28). However, there may be an important dose-response effect in that high levels of lipoperoxides, perhaps through OIW formation, will inactivate prostaglandin and prostacyclin synthases (28).…”

Section: Discussionmentioning

confidence: 99%

Hydrogen peroxide stimulates rat colonic prostaglandin production and alters electrolyte transport.

Karayalçın

Sturbaum²,

Wachsman³

et al. 1990

J. Clin. Invest.

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The changes in short circuit current (electrogenic a-secretion) of rat colon brought about by xanthine/xanthine oxidase in the Ussing chamber were inhibited by catalase and diethyldithiocarbamate, but not by superoxide dismutase. These results, the reproduction of the response with glucose/glucose oxidase and with exogenous H202, and the lack of effect of preincubation with deferoxamine or thiourea implicate H202, and not 02 or OH, as the important reactive oxygen metabolite altering intestinal electrolyte transport. 1 mM H202 stimulated colonic PGE2 and PGI2 production 8-and 15-fold, respectively, inhibited neutral NaCl absorption, and stimulated biphasic electrogenic a secretion with little effect on enterocyte lactic dehydrogenase release, epithelial conductance, or histology. a-secretion was reduced by cyclooxygenase inhibition. Also, the Cl-secretion, but not the increase in prostaglandin production, was reduced by enteric nervous system blockade with tetrodotoxin, hexamethonium, or atropine. Thus, H202 appears to alter electrolyte transport by releasing prostaglandins that activate the enteric nervous system. The change in short circuit current in response to Iloprost, but not PGE2, was blocked by tetrodotoxin. Therefore, PGI2 may be the mediator of the H202 response. H202 produced in nontoxic concentrations in the inflamed gut could have significant physiologic effects on intestinal water and electrolyte transport. (J.

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Section: Discussionmentioning

confidence: 99%

Hydrogen peroxide stimulates rat colonic prostaglandin production and alters electrolyte transport.

Karayalçın

Sturbaum²,

Wachsman³

et al. 1990

J. Clin. Invest.

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“…The PGHS peroxidase exhibits a preference for alkyl hydrophobic peroxides as substrates, with highest activity seen with hydroperoxy-polyunsaturated fatty acids (such as HPETEs) which are slightly more active than PGG 2 [23]. The rate constant for an HPETE is approximately 1000-fold greater than for H 2 O 2 [24].…”

Section: Relation Between Aspirin Efficacy and Cellular Hydroperoxidementioning

confidence: 99%

Acetylation of prostaglandin H2 synthases by aspirin is inhibited by redox cycling of the peroxidase

Bala

Chin

Logan

et al. 2008

Biochemical Pharmacology

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Aspirin exerts its unique pharmacological effects by irreversibly acetylating a serine residue in the cyclooxygenase site of prostaglandin-H 2 -synthases (PGHSs). Despite the irreversibility of the inhibition, the potency of aspirin varies remarkably between cell types, suggesting that molecular determinants could contribute to cellular selectivity. Using purified enzymes, we found no evidence that aspirin is selective for either of the two PGHS isoforms, and we showed that hydroperoxide substrates of the PGHS peroxidase inhibited the rate of acetylation of PGHS-1 by 68%. Using PGHS-1 reconstituted with cobalt protoporphyrin, a heme devoid of peroxidase activity, we demonstrated that reversal by hydroperoxides of the aspirin-mediated acetylation depends upon the catalytic activity of the PGHS peroxidase. We demonstrated that inhibition of PGHS-2 by aspirin in cells in culture is reversed by 12-hydroperoxyeicosatetraenoic acid dose-dependently (ED 50 = 0.58 ± 0.15 μM) and that in cells with high levels of hydroperoxy-fatty acids (RAW264.7) the efficacy of aspirin is markedly decreased as compared to cells with low levels of hydroperoxides (A549; IC 50 s = 256 ± 22 μM and 11.0 ± 0.9 μM, respectively). Together, these findings indicate that acetylation of the PGHSs by aspirin is regulated by the catalytic activity of the peroxidase which yields a higher oxidative state of the enzyme.

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“…29 " 31 However, most of the physiologic roles of HETEs and HPETEs are still unknown. Some lipid hydroperoxides are potent activators of cyclooxygenase, 32 while some can be in- 33 Prostaglandin synthesis is inhibited irreversibly by HPETEs but reversibly by the corresponding HETEs. These HPETEs and HETEs also inhibit the 5-lipoxygenase pathway reversibly.…”

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confidence: 99%

Identification and quantitative analysis of hydroxy-eicosatetraenoic acids in rat brains exposed to regional ischemia.

Usui¹,

Asano²,

Takakura³

1987

Stroke

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To clarify possible roles in the pathogenesis of ischemic brain edema, identification and quantitative analysis of hydroxy-ekosatetraenoic acids (HETEs) in rat brains exposed to middle cerebral artery occlusion were carried out using high-performance liquid chromatography. Rat brain sampling was done by in situ freezing 24 and 72 hours after occlusion. Only a small amount of 15-HETE was found in control rat brains. Twenty-four hours after ischemia, 11-HETE appeared, and the amount of 15-HETE tended to increase. Seventy-two hours after ischemia, when brain edema reached its maximum, 5-, 8-, 9-, 11-, 12-, and 15-HETEs were identified, and the amounts of all HETEs except 8-and 12-HETE were significantly increased. The detection of 5-HETE in ischemic rat brain indicates the simultaneous production of leukotrienes in the same brain area. The above results support the view that lipoxygenase products may play significant roles in the formation of ischemic brain edema. ISCHEMIC cerebral edema is a serious and sometimes fatal complication of stroke, but the precise mechanism of edema formation is not fully understood yet. In recent study of the arachidonate cascade, the possible roles of potent bioactive eicosanoids in various pathologic conditions have been attracting more attention. In the brain, membrane-bound fatty acids were released following ischemic insult or seizure activity.1 " 4 Among these fatty acids, arachidonic acid was shown to cause brain edema and destruction of capillary ehdothelial membranes when injected directly into the brain.5 " 8 Arachidonic acid is a substrate for two oxygenases, and its conversion to various eicosanoids seems to be responsible for these pathologic states. The administration of the cyclooxygenase inhibitor indomethacin did not alleviate ischemic brain edema, or rather aggravated it, 79 " 12 which led us to speculate that lipoxygenase metabolites rather than cyclooxygenase products might play key roles in the pathogenesis of ischemic brain edema, if eicosanoids were involved at all. However, little is known about lipoxygenase metabolism and the pathophysiology of its metabolites in the brain. The following experiments were undertaken to identify the lipoxygenase metabolites and to clarify their relation to ischemic brain edema. Materials and Methods Occlusion Model and Method of Brain SamplingEight male Sprague-Dawley rats weighing about 200 g were anesthetized with 2% halothane, and ac- Received June 17, 1986; accepted November 27, 1986. cording to the method reported elsewhere, 13 they underwent left subtemporal craniectomy. After dural opening, the left middle cerebral artery (MCA) was electrocauterized and severed at the proximal portion just medial to the olfactory tract. In 4 sham-operated rats, the surgical procedure was done in a similar manner except for the MCA occlusion. After surgery, the rats were returned to their cages and fed ad libitum. These rats were anesthetized again with 2% halothane 24 and 72 hours after MCA occlusion. After tracheostomy was performed, ...

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Prostaglandin biosynthesis can be triggered by lipid peroxides

Cited by 335 publications

References 24 publications

Hydrogen peroxide stimulates rat colonic prostaglandin production and alters electrolyte transport.

Hydrogen peroxide stimulates rat colonic prostaglandin production and alters electrolyte transport.

Acetylation of prostaglandin H2 synthases by aspirin is inhibited by redox cycling of the peroxidase

Identification and quantitative analysis of hydroxy-eicosatetraenoic acids in rat brains exposed to regional ischemia.

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