Measurement of gamma-glutamyl transpeptidase and gamma-glutamylcysteine synthetase activities in cells.
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Glutamate-Cysteine Ligase↗
Biomedical subjects
H J Forman
Publications and source records attributed to H J Forman.
Modulation of the alveolar macrophage respiratory burst by hydroperoxides.
Exposure of alveolar macrophages to hydroperoxides (ROOH) inhibits subsequent stimulation of O2.- production (the respiratory burst). Previous studies (under nonoxidant stress conditions) have shown that elevation of intracellular free calcium ([Ca2+]i) participates in both initiation and termination of O2.- production. In this investigation, the effects of sublethal ROOH exposure on [Ca2+]i and the respiratory burst of rat alveolar macrophages were compared. Exposure to a sublethal range of H2O2 or tert-butylhydroperoxide (10-100 pmol/10(6) cells; initially 10-100 microM under the experimental conditions) for 15 min resulted in dose-dependent effects on the respiratory burst stimulated by various agents, ADP, ATP, zymosan-activated serum, and phorbol myristate acetate. Low concentrations of the ROOH (10 or 25 pmol/10(6) cells) were found to enhance stimulation, whereas exposure to 75 or 100 pmol/10(6) cells resulted in significant inhibition for all of the stimuli. All concentrations of ROOH caused a rapid elevation in [Ca2+]i. For those concentrations of ROOH that produced enhancement of subsequent stimulation of the respiratory burst, [Ca2+]i returned to near baseline before the end of the 15-min preincubation. The temporal- and concentration-dependent effects of ROOH on [Ca2+]i correlate with subsequent enhancement or inhibition of stimulated O2.- production. Similarities between the ROOH-induced changes in [Ca2+]i and the effect of [Ca2+]i changes in physiological regulation of the respiratory burst suggest a potential relationship.
Adenosine Diphosphate↗
Detecting and identifying volatile aldehydes as dinitrophenylhydrazones using gas chromatography mass spectrometry.
The detection of aldehydes has become an important measure of lipid oxidation in biological milieu. Aldehyde 2,4-dinitrophenylhydrazones are easily prepared and readily purified by HPLC and/or TLC and have proven useful for the detection of aldehydes. The lower limit of detection for dinitrophenylhydrazones was significantly reduced by using gas chromatography-mass spectrometric (GC-MS) techniques. Individual dinitrophenylhydrazones were readily separated by GC and detected by both positive and negative ion MS. The two major ions in negative ion spectra were the 182 m/z fragment ion and the molecular ion. Positive ion spectra showed strong ions corresponding to the protonated molecular ion and a protonated iminium ion. The greatest sensitivity was obtained with negative ion detection (10 pg per injection). However, more structural information was obtained from analysis of the positive ion spectra. Dinitrophenylhydrazones of hydroxyaldehydes, like 4-hydroxynonenal, were analyzed after converting the dinitrophenylhydrazones into trimethylsiloxylethers. GC-MS with negative ion detection was used to identify and quantitate the release of 4-hydroxynonenal by alveolar macrophages exposed to nitrogen dioxide.
Aldehydes↗
Quinone-induced oxidative stress elevates glutathione and induces gamma-glutamylcysteine synthetase activity in rat lung epithelial L2 cells.
Glutathione (GSH) is one of the most important physiological antioxidants involved in detoxification of hydrogen peroxide and lipid hydroperoxide. Previous studies have shown that cells can maintain and even increase cellular GSH content in response to sublethal oxidative stress. We hypothesized that gamma-glutamylcysteine synthetase (gamma GCS), the rate-limiting enzyme in de novo GSH synthesis, could be induced by oxidative stress. Rat lung epithelial L2 cells were challenged with 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), generates O2.- and H2O2 continuously through redox cycling. Exposure of confluent L2 cells with sublethal doses of DMNQ caused sustained elevation of cellular GSH levels over a 24-h period (to 2.5-fold with 10 microM). DMNQ caused increases in gamma GCS activity (70% at 24 h with 10 microM), the gamma GCS catalytic heavy subunit (gamma GCS-HS) protein level, and gamma GCS-HS mRNA content (approximately 4-fold after 6 h with 10 microM). The elevation of gamma GCS-HS mRNA by DMNQ was eliminated by co-incubation with actinomycin D. Nuclear run-on experiments demonstrated that the transcriptional rate of the gamma GCS-HS gene was increased by 3- or 6-h exposure to 10 microM DMNQ. Our results suggested that the induction of de novo GSH synthesis by naphthoquinone-induced oxidative stress is associated with the transcriptional activation of the gamma GCS-HS gene and the subsequent elevation in gamma GCS activity. Unlike simpler quinones, DMNQ cannot form a GSH conjugate. Thus, the induction of gamma GCS-HS gene transcription does not require formation of an electrophile-glutathione conjugate.
Animals↗
gamma-Glutamylcysteine synthetase and GSH increase in quinone-induced oxidative stress in BPAEC.
Glutathione (GSH), an important physiological antioxidant, is synthesized de novo by the sequential reactions of gamma-glutamylcysteine synthetase (gamma GCS) and GSH synthetase. In the present studies, incubation with the quinones 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) and menadione (MQ), which generate superoxide and hydrogen peroxide, was used to investigate GSH synthesis in bovine pulmonary artery endothelial cells under oxidative stress. MQ can also cause initial depletion of GSH through conjugation, whereas DMNQ cannot. during continuous exposure to DMNQ (5 or 10 microM), elevation of GSH by DMNQ started after 6 h, almost doubled after 24 h, and remained at this level to 48 h. The elevation of GSH by DMNQ was mostly in the reduced form, and the ratio of reduced to oxidized glutathione remained unchanged for the first 24 h. Treatment with MQ (25 or 50 microM) for 30 min caused a significant decrease in GSH and total glutathione. After changing the medium to remove any residual MQ, GSH content doubled during the next 12 h. The enzymatic activity of gamma GCS, the rate-limiting enzyme of GSH biosynthesis, increased twofold after 12 h of exposure of cells to either 5 microM DMNQ or 50 microM MQ. Both DMNQ and MQ treatment caused concentration- and time-dependent increases in gamma GCS-mRNA expression. The elevation of gamma GCS-mRNA content by DMNQ for 12 h was completely blocked by coincubation with 0.05 microgram/ml actinomycin D but not 0.5 microgram/ml cycloheximide, suggesting the elevation of gamma GCS-mRNA content occurred through increased transcription. Our results suggest that increased de novo GSH synthesis, mediated by an elevation in gamma GCS, constitutes an adaptive response to oxidative stress.
Animals↗
gamma-Glutamyl transpeptidase is increased by oxidative stress in rat alveolar L2 epithelial cells.
The tripeptide glutathione (GSH) is used by cells to detoxify hydroperoxides, produced during oxidative stress, and is consumed in the process. Previous studies have indicated that cells can be protected against oxidative stress by extracellular GSH through its degradation catalyzed by the exoenzyme gamma-glutamyl transpeptidase (gamma GT) and its de novo synthesis within the cytosol. We hypothesized that gamma GT would be increased as part of the adaptation of cells to oxidative stress. We examined whether oxidative stress could increase gamma GT activity, protein, and mRNA in a lung epithelial cell line (L2). Cultures were subjected to H2O2-mediated toxicity by 15 min of exposure to the redox cycling quinone, menadione. Menadione (50 microM) caused an initial decrease (27 +/- 9% of baseline after 15 min) in intracellular GSH, followed by resynthesis to levels significantly higher than baseline (335 +/- 40% after 24 h, P < 0.001). This elevation was prevented by acivicin, a gamma GT inhibitor. Menadione also caused a dose-dependent increase in gamma GT enzymatic activity (715 +/- 125% of control at 24 h after 15 min of exposure to 100 microM menadione, P < 0.001) that was prevented by actinomycin D. Western blot analysis indicated increased levels of gamma GT protein with increasing menadione. A concentration-dependent increase in gamma GT-mRNA was also observed. Previous investigation has demonstrated that an increase in gamma GT activity enhances the capacity of cells to utilize extracellular GSH. The findings presented here are consistent with a role for gamma GT in cellular adaptation to oxidative stress.
Animals↗
Extracellular glutathione and gamma-glutamyl transpeptidase prevent H2O2-induced injury by 2,3-dimethoxy-1,4-naphthoquinone.
Quinones are intracellular H2O2 generators that have been used extensively in models of oxidant injury; however, their toxicity is mediated partially through direct conjugation with glutathione (GSH). To focus upon the action of extracellular GSH in preventing H2O2-mediated toxicity, we used 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), which cannot conjugate with GSH but does continuously generate H2O2 through redox cycling. A eukaryotic cell line (3T3-GGT) stably overexpressing gamma-glutamyl transpeptidase (GGT) activity was used to study the role of GGT in utilizing extracellular GSH against DMNQ-induced oxidative stress. DMNQ (0 to 150 microM) caused a dose-dependent decrease of intracellular GSH and adenosine 5'-triphosphate (ATP) in both control and 3T3-GGT cells. The rate of H2O2 escape into the medium during DMNQ exposure was also the same in both cell lines. Administration of GSH helped to maintain intracellular GSH and supported resistance to ATP depletion caused by DMNQ in 3T3-GGT cells but not in control cells. The protective effect of extracellular GSH was completely prevented by acivicin, an inhibitor of GGT. Our results suggest that GGT-dependent breakdown of extracellular GSH for subsequent intracellular resynthesis helped to maintain cellular GSH levels and increased cellular resistance against DMNQ-induced oxidative injury.
3T3 Cells↗
Depression of stimulated arachidonate metabolism and superoxide production in rat alveolar macrophages following in vivo exposure to 0.5 ppm NO2.
Alveolar macrophages (AM) have been found to suffer significant functional deficits in response to nitrogen dioxide (NO2) exposure. The present investigation examined changes in the activation of AM arachidonate metabolism and superoxide production in response to an environmentally relevant level of NO2. Rats were exposed to 0.5 ppm NO2 for periods of 0.5-10 d and AM were obtained by bronchoalveolar lavage (BAL). NO2 exposure produced complex effects upon both unstimulated and stimulated AM arachidonate metabolism. Unstimulated AM synthesis of leukotriene B4 (LTB4) was depressed rapidly within 1 d of exposure, and depressed again at 5 d. Alveolar macrophage production of thromboxane B2 (TxB2), LTB4, and 5-hydroxyeicosatetraenoate (5-HETE) in response to stimulation with the calcium ionophore, A23187, were acutely depressed within 1 d of exposure; however, generation of these compounds recovered to air-control levels with longer exposure, while 5-HETE was increased at 10 d. In contrast, AM production of LTB4 in response to another stimulus, zymosan-activated rat serum (ZAS), was not depressed until following 5 d of exposure and remained slightly lower than air-control levels at 10 d. Levels of TxB2, LTB4, prostaglandin E2 (PGE2), and prostaglandin F2 alpha (PGF2 alpha) measured in BAL fluid (BALF) were found to be depressed within 4 h of exposure, suggesting an acute decrease in the in vivo pulmonary arachidonate metabolism; however, production of these compounds generally recovered to air-control levels with longer exposure. The AM superoxide production stimulated by phorbol myristate acetate (PMA) was decreased rapidly and continuously throughout the study. Thus, exposure to a low concentration of NO2 acutely depresses activation of AM arachidonate metabolism and superoxide production in response to external stimuli, and may impede defense against pulmonary infection.
Animals↗
Effects of sodium and proton pump activity on respiratory burst and pH regulation of rat alveolar macrophages.
At pH 7.4, extracellular Na+ removal inhibited the rat alveolar macrophage respiratory burst (RB) stimulated by phorbol 12-myristate 13-acetate (PMA) or zymosan-activated serum (ZAS). At pH 6.8, the RB was lower and decreased the Na+ effect. Amiloride inhibited the ZAS RB independently of effects on Na(+)-H+ exchange, but did not affect PMA stimulation. NBD-Cl, an H(+)-ATPase inhibitor, significantly inhibited the PMA or ZAS RB. Na+ removal caused sustained elevation of intracellular free [Ca2+], which previous studies suggested inhibits the RB. Intracellular pH (pHi) was lower at pHo 6.8 compared with pHo 7.4, but not altered by Na+ removal. PMA stimulation resulted in acidification corresponding with onset of superoxide production. At pHo 7.4, recovery to baseline pHi occurred that was not inhibited by amiloride or Na+ removal. In contrast, amiloride slowed pHi recovery after an exogenous acid load. Addition of H(+)-ATPase inhibitors, NBD-Cl or bafilomycin, following PMA stimulation or acid loading, inhibited pHi restoration. These studies suggest that pHi regulation following stimulation was mainly through a proton pump, whereas Na(+)-H+ exchange occurred only after greater acid loading. Nevertheless, Na+ and pH interacted to modulate the RB independent of Na(+)-H+ exchange.
4-Chloro-7-nitrobenzofurazan↗
Stimulation of the rat alveolar macrophage respiratory burst by extracellular adenine nucleotides.
Exogenous nucleotides can serve as extracellular factors that cause significant functional changes in numerous cells, including phagocytes. In the current study, addition of ATP, ADP, and ATP gamma S directly stimulated the respiratory burst (superoxide production) by rat alveolar macrophages, whereas adenosine and AMP did not. The relative potency of these nucleotides at saturating concentration was ADP > or = ATP gamma S >> ATP; however, simultaneous addition of maximally stimulatory concentrations of ADP and ATP (100 microM of each) produced an additive effect suggesting involvement of two P2 receptors. Following addition of the nucleotides, an elevation of intracellular Ca2+ ([Ca2+]i) occurred within seconds, followed by a decline within 1 min but with a prolonged elevation above baseline for at least 5 min. Removal of extracellular Ca2+ only slightly attenuated the initial elevation, indicating that adenine nucleotides stimulate the rapid release of intracellular Ca2+ stores. Removal of extracellular Ca2+ also eliminated the sustained elevation in [Ca2+]i and markedly suppressed the respiratory burst. Incubation with verapamil, a Ca2+ channel blocker, also significantly inhibited the respiratory burst stimulated by ATP. These studies demonstrate that adenine nucleotides stimulate a Ca(2+)-dependent respiratory burst by rat alveolar macrophages, probably through purinergic receptors.
Adenine Nucleotides↗
Sublethal oxidant stress induces a reversible increase in intracellular calcium dependent on NAD(P)H oxidation in rat alveolar macrophages.
A concentration-dependent elevation of intracellular calcium ([Ca2+]i) and oxidation of NAD(P)H occurred in alveolar macrophages during exposure to sublethal tert-butylhydroperoxide concentrations (tBOOH) (< or = 100 microM in 1 ml with 1 x 10(6) cells). Oxidation of NAD(P)H preceded a rise in [Ca2+]i. The elevation of [Ca2+]i was reversible at < 50 microM tBOOH exposure and the return to the steady state [Ca2+]i correlated temporally with repletion of NAD(P)H. At > 50 microM tBOOH, the changes in NAD(P)H and [Ca2+]i were sustained. The relative contributions of NADPH and NADH oxidation were examined by varying the substrates supplying reducing equivalents and by inhibiting glutathione reductase activity. The results suggested that at < 50 microM tBOOH, oxidation of NADPH predominated, while at > 50 microM tBOOH, NADH oxidation predominated. A complex relationship between the relative roles of NADPH and NADH oxidation and the elevation of [Ca2+]i was revealed: (i) reversible oxidation of NADPH is associated with the initial and reversible elevation of [Ca2+]i at < 50 microM tBOOH; (ii) the sustained elevation of [Ca2+]i at > 50 microM tBOOH correlates with the sustained oxidation of NADH; and (iii) the changes in [Ca2+]i did not depend on influx of extracellular Ca2+. We speculate that at low tBOOH, Ca2+ was released from the NADPH/NADP(+)-sensitive mitochondrial Ca2+ pool while higher tBOOH caused additional Ca2+ release from GSH/GSSG-sensitive nonmitochondrial Ca2+ pools with sustained elevation of [Ca2+]i due to decreased mitochondrial Ca2+ reuptake.
Animals↗
Transfection with gamma-glutamyl transpeptidase enhances recovery from glutathione depletion using extracellular glutathione.
Glutathione (L-gamma-glutamyl-L-cysteinylglycine) is an important constituent of the antioxidant and detoxifying mechanisms of cells. The plasma membrane bound enzyme, gamma-glutamyl transpeptidase (GGT), catalyzes the first step in the degradation of extracellular glutathione, the components of which are then used for de novo glutathione synthesis. We tested the hypothesis that an increase in GGT activity would enhance the utilization of extracellular glutathione by cells challenged with a glutathione-depleting agent. A eukaryotic system stably overexpressing GGT (nearly 200-fold) was developed by transfection of NIH-3T3 fibroblasts with a human placental GGT cDNA. These cells and controls were incubated for 30 min with 1 mM diethyl maleate, which caused approximately 80% intracellular glutathione depletion. Glutathione was added to the medium and cells were allowed to resynthesize intracellular glutathione. The transfected cells used extracellular glutathione much more efficiently than controls in terms of both the concentration dependence and the rate of glutathione resynthesis. Serine-borate, a competitive inhibitor of GGT, blocked the restoration of intracellular glutathione. The results support the hypothesis that the increase in GGT activity that occurs in some toxicologic or pathologic conditions could provide protection against glutathione depletion.
Animals↗
Exogenous glutathione protects endothelial cells from menadione toxicity.
Administration of menadione (vitamin K3; 2-methyl-1,4-naphthoquinone) to cultured bovine pulmonary artery endothelial cells caused a dose- and time-dependent depletion of cellular ATP and depletion of intracellular glutathione (GSH). The toxicity of menadione was correlated with an increase of menadione-glutathione conjugate in the medium and with an increase in H2O2 generation. Recent studies have suggested that GSH may be useful as a pharmacological agent to prevent oxidant injury. In the present study, treatment with exogenous GSH prevented the loss of cellular GSH and ATP caused by menadione. Protection by extracellular GSH involved two mechanisms. In one mechanism, extracellular GSH was degraded by gamma-glutamyl transpeptidase, producing substrates for subsequent intracellular de novo GSH synthesis. We found that the protective effect of extracellular GSH was decreased by inhibiting gamma-glutamyl transpeptidase. In the other mechanism, GSH reacted in the medium with menadione to form a conjugate. Although formation of the menadione-glutathione conjugate within cells may contribute to menadione toxicity, addition of menadione-glutathione conjugate to the medium was found to be nontoxic to endothelial cells. Thus exogenous GSH protected endothelial cells by two mechanisms: maintenance of intracellular GSH and prevention of menadione entrance into cells.
Adenosine Triphosphate↗
Identification of a human gamma-glutamyl cleaving enzyme related to, but distinct from, gamma-glutamyl transpeptidase.
We have cloned a 2.4-kilobase cDNA from a human placental cDNA library by using a gamma-glutamyl transpeptidase [GGT; gamma-glutamyltransferase, (5-glutamyl)-peptide:amino acid 5-glutamyltransferase, EC 2.3.2.2] probe. The deduced amino acid sequence of this cDNA, GGT-rel, exhibited an overall similarity of 39.5% with human GGT. Sequences that could represent a heavy and a light chain, analogous to GGT, as well as a putative transmembrane region were identified in GGT-rel. Transfectants overexpressing GGT-rel were tested for their ability to catalyze cleavage of the gamma-glutamyl moiety from natural and synthetic substrates for GGT. Experiments with glutathione added to the medium suggested that GGT-rel could hydrolyze the gamma-glutamyl moiety. More definitive evidence was obtained in experiments in which this protein converted leukotriene C4 to leukotriene D4. However, GGT-rel did not convert synthetic substrates that are commonly used to assay GGT. Our results indicate that GGT can no longer be considered the only enzyme capable of cleaving the gamma-glutamyl linkage of leukotriene C4 and, most likely, of other natural compounds.
Amino Acid Sequence↗
Augmentation of superoxide dismutase and catalase activity in alveolar type II cells.
This study tested whether adducts formed by covalent linkage of superoxide dismutase (SOD) or catalase to polyethylene glycol (PEG) could augment SOD and catalase activity in alveolar type II cells and document enhanced resistance to oxidant damage. Alveolar type II cells were isolated from adult, pathogen-free rats. Antioxidant enzymes were added to the medium of cell cultures in various concentrations for periods up to 48 h. Incubation with 500 to 3,000 U of PEG-SOD or 10,000 to 40,000 U of PEG-catalase/10(6) cells produced a dose-response-related increase in intracellular enzyme activity in comparison with controls (untreated or treated with SOD or catalase, inactivated PEG-SOD or PEG-catalase, or PEG alone). Uptake was maximal during the first 4 h. Using fluorescent label (fluorescein isothiocyanate) bound to PEG-catalase, we found intracellular localization of the labeled enzyme. Exposure to H2O2 led to reduced cytotoxicity in cells pretreated with PEG-catalase than in controls. We conclude that supplementation with PEG-SOD or PEG-catalase enhanced the activity of these enzymes in alveolar type II cells and increased their resistance to oxidant stress.
Animals↗
Inhibition of production of LTB4 and chemotactic agent from rat alveolar macrophages treated with t-butyl hydroperoxide is independent of ATP depletion.
In rat alveolar macrophages treated with 100 microM t-butyl hydroperoxide (tBOOH), leukotriene B4 (LTB4) synthesis was significantly lower than the basal level while levels of cyclooxygenase pathway products were increased. LTB4, 5,6-dihydroxyeicosatetraenoic acid (5,6-DiHETEs), and 5-hydroxyeicosatetraenoic acid (5-HETE) production in macrophages was significantly stimulated by 2 microM A23187, but this was suppressed 40% by simultaneous addition of 10 microM tBOOH and completely abolished by 100 microM tBOOH. Basal and A23187-stimulated macrophage production of chemotactic agents were similarly suppressed by addition of tBOOH; this effect paralleled depression of cellular LTB4 synthesis. In contrast to the significant depression of A23187-stimulated formation of 5-lipoxygenase products by 10 microM tBOOH, cellular adenosine triphosphate (ATP) was unchanged. Macrophages pretreated with KCN led to a 42% decline in ATP levels; however, LTB4, 5,6-DiHETEs, and 5-HETE production in response to A23187 was not suppressed. The results indicate that inhibition of 5-lipoxygenase pathway products in macrophages treated with tBOOH did not occur by depletion of cellular ATP levels.
Adenosine Triphosphate↗
Inhibition of arachidonic acid release by nordihydroguaiaretic acid and its antioxidant action in rat alveolar macrophages and Chinese hamster lung fibroblasts.
The ability of nordihydroguaiaretic acid (NDGA) to inhibit arachidonic acid (AA) release from rat alveolar macrophages treated with t-butyl hydroperoxide (tBOOH) or from Chinese hamster lung fibroblasts (V79 cells) treated with linoleic acid hydroperoxide (LOOH) was examined. Treatment of alveolar macrophages with 100 microM tBOOH significantly increased arachidonic acid release and its conversion to metabolites. Pretreatment of macrophages with NDGA (greater than or equal to 2.5 microM) inhibited the release of AA and its subsequent metabolism following addition of tBOOH. Treatment of V79 cells with 1 microM LOOH stimulated the release of AA. Pretreatment with either 1 or 10 microM NDGA prior to the addition of LOOH inhibited the release of AA. A23187 (2 microM)-stimulated release of AA from V79 cells was less sensitive to NDGA inhibition. Pretreatment with 10 microM NDGA, but not with 1 microM NDGA, inhibited A23187-stimulated release of AA. PLA2-dependent hydrolysis of micelle preparations of disaturated phosphatidylcholine was not inhibited by NDGA. Previous studies have suggested that the addition of peroxides alters cells by inducing lipid peroxidation so that the action of phospholipases upon their membranes is enhanced. The results suggest that NDGA, a lipid-soluble antioxidant which traps free radicals, indirectly blocked the action of phospholipases upon cell membranes by inhibiting lipid peroxidation.
Animals↗
t-Butyl hydroperoxide stimulates alveolar macrophage biosynthesis of cyclooxygenase products.
Rat alveolar macrophages, labeled with 3H-arachidonic acid, were treated with t-butyl hydroperoxide (tBOOH). Treatment of cells with 100 microM tBOOH led to a rapid increase in 12-hydroxyheptadecatrienoic acid (12-HHT) within 2.5 minutes. At 15 minutes, 12-HHT levels appeared to plateau as there was no further increase at 30 minutes. TxB2 levels increased in a similar manner to that found with 12-HHT; however, only the level at 15 minutes was statistically increased. TxB2 levels also appeared to plateau at 15 minutes. Indomethacin, at a concentration of 1 microM, significantly inhibited TxB2 and 12-HHT production by approximately 90%. Desferal, an iron chelator, had no effect on alterations of biosynthesis of cyclooxygenase products by macrophages treated with tBOOH. No evidence of lipoxygenase products was found. Thus, these results suggest that tBOOH rapidly and selectively stimulated arachidonic acid metabolism through the cyclooxygenase pathway in rat alveolar macrophages. The stimulation of cyclooxygenase activity was transient with a maximum rate observed at 100 microM tBOOH.
Animals↗