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Biomedical subjects

S Parthasarathy

Publications and source records attributed to S Parthasarathy.

At least 37 records · Page 2Linked to original sources
PubMed2001

3',4'-Bis(4-chlorophenyl)spiro[chroman-3,5'(4'H)-isoxazol]-4-one.

The title compound, C(23)H(15)Cl(2)NO(3), crystallizes with two independent molecules in the asymmetric unit. The chromanone moiety consists of a benzene ring fused with a six-membered heterocyclic ring which adopts a sofa conformation. The five-membered spiroisoxazoline ring is in an envelope conformation. The p-chlorophenyl rings bridged by the five-membered ring are nearly perpendicular to each other. The chromanone moiety of one molecule packs into the cavity formed by the p-chlorophenyl rings of a second molecule through the formation of C-H.pi interactions. The structure is stabilized by weak C-H.O, C-H.Cl and C-H.pi interactions.

Journal Article↗
PubMed2001

Role of arterial wall antioxidant defense in beneficial effects of exercise on atherosclerosis in mice.

The mechanism(s) by which exercise reduces atherogenic risk remains unknown. This study tested the hypothesis that sustained exercise-induced oxidative stress may increase antioxidant defense in the arterial wall. Acute exercise induced an increase in antibodies to oxidatively modified proteins and catalase in the aortic walls of normal mice compared with sedentary control mice. In male atherogenic diet-fed low density lipoprotein (LDL) receptor-deficient mice, exercise lowered plasma cholesterol (15%) and decreased atherosclerotic lesions by 40% compared with values in sedentary control mice, with a concomitant increase in arterial catalase and endothelial NO synthase. Because these mice lack the LDL receptor, the results indicate that the LDL receptor might not be responsible for the exercise-induced lowering of plasma cholesterol. Vitamin E supplementation to exercising LDL receptor-deficient mice did not reduce atherosclerotic lesion formation significantly as opposed to lesion formation in untreated exercised mice. Moreover, vitamin E counteracted the beneficial effects of exercise by preventing the induction of aortic catalase activity and endothelial NO synthase expression. These results might indicate that although vitamin E might have prevented the exercise-induced oxidative stress, its availability in the artery was insufficient to prevent the atherosclerotic process. These results indicate that exercise-induced plasma oxidative stress could be responsible for the prevention of atherosclerosis by stimulating arterial antioxidant response. Furthermore, vitamin E supplementation could be deleterious in exercisers by inhibiting antioxidant enzyme buildup in the arterial wall.

Animals↗
PubMed2001

Expression of scavenger receptor class B1 in endometrium and endometriosis.

Endometriosis is characterized by the presence of endometrial glands and stroma within the peritoneum and other extrauterine sites. The presence of aromatase, a key enzyme in the biosynthesis of estradiol, has been demonstrated in eutopic endometrial samples of women with moderate to severe endometriosis, but not in those of disease-free women. Animal studies have shown that high density lipoprotein provides precursor cholesterol pool for steroidogenesis. Scavenger receptor class B1, a 82-kDa cell surface protein, is involved in the binding of high density lipoprotein to target cells and promotes cholesteryl ester uptake. In this study we detected the presence of scavenger receptor class B1 in eutopic and ectopic endometrium. There was more scavenger receptor class B1 protein associated with endometriosis compared with matched endometrium. Two bands (82 and 45 kDa) were detected in the endometrium and endometriosis samples. Glycanase treatment indicated that the 45-kDa protein might be a nonglycosylated form of scavenger receptor class B1. Immunostaining of fixed tissues detected scavenger receptor class B1 in glandular epithelium of both tissues. Scavenger receptor class B1 and aromatase mRNA were increased in endometriosis tissues. Scavenger receptor class B1 expression in the endometrium and endometriosis supports a role for this receptor in the uptake of high density lipoprotein cholesterol, possibly supporting in situ estrogen production, which is detrimental in the progression of endometriosis.

Adult↗
PubMed2001

Association of outpatient alcohol and drug treatment with health care utilization and cost: revisiting the offset hypothesis.

OBJECTIVE: This study examines the hypothesis that treatment reduces medical utilization and costs of patients with substance use problems. METHOD: Adult patients (N = 1.011; 67% men) entering the outpatient chemical dependency recovery program at Sacramento Kaiser Permanente over a 2-year period were recruited into the study. Medical utilization and costs were examined for 18 months prior and 18 months after intake. To account for overall changes in utilization and cost, an age, gender and length-of-enrollment matched nonpatient control group (N = 4,925) was selected from health-plan members living in the same service area. Multivariate analyses controlling for age and gender were conducted using generalized estimating equation methods, allowing for correlation between repeated measures and nonnormal distributions of the outcome variable. RESULTS: The treatment cohort was less likely to be hospitalized (odds ratio [OR] = 0.59; p < .01) and there was a trend for having spent fewer days (rate ratio [RR] = 0.77; p < .10) in the hospital in the posttreatment period compared to pretreatment period. These patients were also less likely to visit the emergency room (ER) (OR = 0.64; p < .01) and had fewer ER visits (RR = 0.81; p < .01) following treatment. Inpatient, ER and total medical costs declined by 35%, 39% and 26%, respectively (p < .01). Reductions in cost were greater for the treatment cohort when compared with the matched sample (p < .05). Among women, there were significant reductions (p < .05) in inpatient, ER and total costs for the study cohort when compared with the matched sample; among men, the reductions in inpatient and ER cost (but not total cost) were significantly larger (p < .05) for the study cohort when compared with the matched sample. For the treatment cohort, the change in medical cost was not significantly different by gender. Changes in cost were significantly different across the various age groups (p < .05) for the study cohort and the matched sample. Among those in the group aged 40-49 years, the decline in cost for study cohort was significantly larger (p < .05) than for the matched sample. CONCLUSIONS: For patients with substance use disorders entering treatment, there was a substantial decline in inappropriate utilization and cost (hospital and ER) in the posttreatment period. The disaggregated pattern of posttreatment decline in utilization and cost is suggestive of long-term reductions that warrant a longer follow-up.

Adolescent↗
PubMed2001

Improving alcoholism treatment across the spectrum of services.

This article represents the proceedings of a symposium at the 2000 RSA Meeting in Denver, Colorado. The chair was Michael E. Hilton. The presentations were (1) The effects of brief advice and motivational enhancement on alcohol use and related variables in primary care, by Stephen A. Maisto, Joseph Conigliaro, Melissa McNiel, Kevin Kraemer, Mary E. Kelley, and Rosemarie Conigliaro; (2) Enhanced linkage of alcohol dependent persons to primary medical care: A randomized controlled trial of a multidisciplinary health evaluation in a detoxification unit, by Jeffrey H. Samet, Mary Jo Larson, Jacqueline Savetsky, Michael Winter, Lisa M. Sullivan, and Richard Saitz; (3) Cost-effectiveness of day hospital versus traditional alcohol and drug outpatient treatment in a health maintenance organization: Randomized and self-selected samples, by Constance Weisner, Jennifer Mertens, Sujaya Parthasarathy, Charles Moore, Enid Hunkeler, Teh-Wei Hu, and Joe Selby; and (4) Case monitoring for alcoholics: One year clinical and health cost effects, by Robert L. Stout, William Zywiak, Amy Rubin, William Zwick, Mary Jo Larson, and Don Shepard.

Alcoholism↗
PubMed2000

RU486-induced growth inhibition of human endometrial cells.

OBJECTIVE: To determine the direct action of RU486 on endometrial cell proliferation and to differentiate whether the antioxidant or the antiprogesterone property of RU486 is predominately responsible for its effect on cell growth. DESIGN: In vitro study comparing the effects of RU486 (antiprogesterone and antioxidant), reduced RU486 (antioxidant), ZK112,993 (antiprogesterone), and lazaroid U74,500A (antioxidant) on endometrial cell growth. The human endometrial cell line EM42 was used in transient transfection assays to confirm the relative antiprogesterone potency of the various compounds. SETTING: Academic medical center PATIENT(S): Women presenting with pelvic pain or infertility and diagnosed with endometriosis at time of surgery or women desiring tubal ligation with a normal pelvis (controls). INTERVENTION(S): Endometrial cell cultures were treated with RU486, reduced RU486, lazaroid U74,500A, and ZK112,993. MAIN OUTCOME MEASURE(S): Tritiated thymidine incorporation was used to assess cell growth. Inhibition of progesterone induction of transiently transfected reporter plasmids was used to measure antiprogesterone activity of compounds studied. RESULT(S): RU486 reduced cell growth in a dose-dependent fashion of the endometrial cell lines EM42 and RL95-2 and of endometrial and endometriosis cells from primary culture. After being reduced, RU486 lost most of its antiprogesterone activity but retained its antiproliferative properties. ZK112,993 was similar in potency to RU486 as a progesterone antagonist but did not significantly modify endometrial cell growth. Lazaroid U74,500A was devoid of antiprogesterone activity but was shown to be a potent antiproliferative agent. CONCLUSION(S): RU486 has a direct inhibitory effect on human endometrial cell growth. This activity appears to be at least partly mediated through its antioxidant property.

Antioxidants↗
PubMed2000

Implications in the maintenance of pregnancy: I. Presence of immunoreactive glycodelin in human umbilical cord vein endothelial cells.

OBJECTIVE: We previously reported an antipeptide antibody to human glycodelin that recognizes glycodelin in amniotic fluid and epithelial glands of the endometrium. The objective of this study was to determine the presence of glycodelin in human umbilical cord. DESIGN: Controlled clinical study. SETTING: Healthy women undergoing normal delivery at Grady Memorial Hospital, Atlanta, Georgia. PATIENT(S): Healthy women undergoing normal delivery. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Umbilical cord vein was isolated from the cord and used for immunohistochemical studies. Human umbilical cords and placentae were collected after full-term delivery. Cords were washed and fixed with formal sucrose. Decidua tissues and blood vessels from placentae were dissected out and fixed. Cryostat sections were immunostained with anti-glycodelin peptide antibody and anti-von Willebrand factor antibody. RESULT(S): Endothelial cells of human umbilical cord vein and artery were strongly immunostained with antiglycodelin antibody. Endothelial cells of the vein were more strongly stained than those of the artery. These cells were confirmed as endothelial cells by positive immunostaining with anti-von Willebrand factor. The epithelial cells outlining the cord were stained with antiglycodelin antibody but not with anti-von Willebrand factor antibody. CONCLUSION(S): This is the first study showing that immunoreactive glycodelin is present in endothelial cells of the umbilical cord. Glycodelin in the umbilical cord may have immunosuppressive or other, unknown functions affecting the physiology or pathophysiology of pregnancy. Whether umbilical vein endothelial cells synthesize glycodelin or serve as reservoir for glycodelin is currently under investigation.

Case-Control Studies↗
PubMed2000

Implications in the management of pregnancy: II. Low levels of gene expression but enhanced uptake and accumulation of umbilical cord glycodelin.

OBJECTIVE: We recently reported the presence of glycodelin in the endothelial cells of human umbilical cord. The objective of the current study is to determine whether human umbilical cord endothelial cells synthesize glycodelin. DESIGN: Controlled clinical study. SETTING: Healthy women undergoing normal delivery at Grady Memorial Hospital, Atlanta, Georgia. PATIENT(S): Healthy women undergoing normal delivery. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Human umbilical cord was collected after full-term delivery and total RNA from endothelial cells was isolated. Reverse-transcription polymerase chain reaction (RT-PCR) was performed by using primers from glycodelin sequence. Human umbilical cord endothelial cells at passage 3 were incubated with glycodelin-derived peptide or glycodelin-rich amniotic fluid. Immunocytochemical analysis was performed by using purified chicken anti-glycodelin peptide antibody to detect the accumulation of glycodelin in cells. RESULT(S): Little or no glycodelin message was detectable in the endothelial cells from human umbilical cord vein by RT-PCR and Southern blot analysis. However, these cells readily took up glycodelin protein and glycodelin-derived synthetic peptide from the medium. CONCLUSION(S): The presence and accumulation of glycodelin in the umbilical cord might indicate their potential role in the survival of fetal tissue in the maternal environment.

Blotting, Western↗
PubMed2000

Hypercapnic respiratory failure during weaning: neuromuscular capacity versus muscle loads.

Patients who fail a weaning trial develop hypercapnia as a result of alveolar hypoventilation, which, in turn, is caused by an imbalance between the respiratory muscle load and capacity. In some patients, especially those with obstructive lung diseases, respiratory muscle performance is impaired as a result of dynamic hyperinflation and paradoxical motion of the rib cage and abdomen. Worsening of pulmonary mechanics causes further embarrassment of the respiratory muscles and can lead to marked alterations of oxygen use by the peripheral tissues. The development of rapid shallow breathing together with worsening of pulmonary mechanics results in inefficient clearance of COcf152cf1 during a failed weaning attempt.

Humans↗
PubMed2000

Potential role of oxidized lipids and lipoproteins in antioxidant defense.

The atherogenic oxidative modification of low-density lipoprotein is suggested to occur in the aortic intima. There is reasonable evidence to suggest that antioxidants might be beneficial in preventing or retarding the progression of atherosclerosis. Exercise, estrogens, and substitution of polyunsaturated fat for saturated fat are beneficial in the prevention of atherosclerosis. Yet, paradoxically, they are capable of inducing an oxidative stress. To reconcile with this paradox, we postulate that under certain conditions an oxidative stress might be beneficial by inducing antioxidant enzymes in arterial cells. However, those with genetic deficiency in antioxidant enzymes or those who poorly respond to oxidative stress or those with overwhelming plasma oxidative stress might need additional antioxidant protection.

Animals↗
PubMed2000

Protein thermal stability: insights from atomic displacement parameters (B values).

The factors contributing to the thermal stability of proteins from thermophilic origins are matters of intense debate and investigation. Thermophilic proteins are thought to possess better packed interiors than their mesophilic counterparts, leading to lesser overall flexibility and a corresponding reduction in surface-to-volume ratio. These observations prompted an analysis of B values reported in high-resolution X-ray crystal structures of mesophilic and thermophilic proteins. In this analysis, the following aspects were addressed: (1) frequency distribution of normalized B values (B' factors) over all the proteins and for individual amino acids; (2) amino acid compositions in high B value regions of polypeptide chains; (3) variation in the B values from core to the surface of proteins in terms of their radius of gyration; and (4) degree of dispersion of normalized B values in spheres around the Calpha atoms. The analysis revealed that (1) Ser and Thr have lesser flexibility in thermophiles than in mesophiles, (2) the proportion of Glu and Lys in high B value regions of thermophiles is higher and that of Ser and Thr is lower and (3) the dispersion of B values within spheres at Calpha atoms is similar in mesophiles and thermophiles. These observations reflect plausible differences in the dynamics of thermophilic and mesophilic proteins and suggest amino acid substitutions that are likely to change thermal stability.

Amino Acids↗
PubMed2000

Assessment of neural inspiratory time in ventilator-supported patients.

Neural inspiratory time (TI) is a measurement of fundamental importance in studies of patient-ventilator interaction. The measurement is usually based on recordings of flow, esophageal pressure (Pes), and transdiaphragmatic pressure (Pdi), but the concordance of such estimates of neural TI with a more direct measurement of neural activity has not been systematically evaluated. To address this issue, we studied nine ventilator-supported patients in whom we employed esophageal electrode recordings of the diaphragmatic electromyogram (EMG) as the reference measurement of neural TI. Comparison of the indirect estimates of neural TI duration, based on flow, Pes, and Pdi against the reference measurement, revealed a mean difference (bias) ranging from -54 to 612 ms during spontaneous breathing and from -52 to 714 ms during mechanical ventilation; the respective precisions (standard deviations of the differences) ranged from 79 to 175 ms and from 74 to 221 ms. Because an indirect estimate of neural TI duration could be identical to that of the reference measurement and yet be displaced in time, this lag or lead was quantified as the phase angle of neural TI onset. Flow-based estimates of the onset of neural TI displayed a systematic lag, which may be explained at least in part by concurrent intrinsic positive end-expiratory pressure. In conclusion, the indirect estimates of the onset and duration of neural TI in ventilator-dependent patients displayed poor agreement with the diaphragmatic EMG measurement of neural TI.

Aged↗
PubMed2000

Lipid peroxides induce expression of catalase in cultured vascular cells.

Various forms of oxidized low-density lipoproteins (Ox-LDL) are thought to play a major role in the development of atherosclerosis. The lipid components of Ox-LDL present a plethora of proatherogenic effects in in vitro cell culture systems, suggesting that oxidative stress could be an important risk factor for coronary artery disease. However, buried among these effects are those that could be interpreted as antiatherogenic. The present study demonstrates that various oxidants, including oxidized fatty acids and mildly oxidized forms of LDL (MO-LDL), are able to induce catalase (an antioxidant enzyme) expression in rabbit femoral arterial smooth muscle cells (RFASMC), RAW cells (macrophages), and human umbilical vein endothelial cells (HUVEC). In RFASMC, catalase protein, mRNA, and the enzyme activity are increased in response to oxidized linoleic acid (13-hydroperoxy-9,11-octadecadienoic acid [13-HPODE] and 13-hydroxy-9,11-octadecadienoic acid [13-HODE]), MO-LDL, or hydrogen peroxide (H(2)O(2)). Such an increase in catalase gene expression cannot totally be attributed to the cellular response to an intracellular generation of H(2)O(2) after the addition of 13-HPODE or 13-HODE because these agents induce a further increase of catalase as seen in catalase-transfected RFASMC. Taken together with the induction of heme oxygenase, NO synthase, manganese superoxide dismutase (Mn-SOD), and glutathione synthesis by oxidative stress, our results provide yet more evidence suggesting that a moderate oxidative stress can induce cellular antioxidant response in vascular cells, and thereby could be beneficial for preventing further oxidative stress.

Animals↗
PubMed2000

Dietary oxidized fatty acids: an atherogenic risk?

Previous studies have suggested that heated fat that contains oxidized fatty acids in the diet might contribute to the presence of oxidized components in circulating lipoproteins. On the other hand, studies in our laboratory showed that cultured cells such as smooth muscle cells take up oxidized fatty acids poorly. Because intestinal cells are morphologically quite distinct, we studied the uptake of oxidized linoleic acid by Caco-2 and smooth muscle cells (control). When 16-day-old Caco-2 cells were incubated with oxidized linoleic acid (ox-linoleic acid), its uptake was comparable to that of unoxidized linoleic acid (unox-linoleic acid) or that of oleic acid (40;-58, 70, and 55%, respectively). In contrast, the uptake of ox-linoleate by smooth muscle cells was about 3%. To determine whether the brush border structure of Caco-2 cells was responsible for increased uptake of oxidized fatty acids, we compared uptake in 4- and 16-day-old cells. The uptake of unox-linoleate and oleic acid (18:1) was comparable for the 4- and 16-day cells. In addition, saturation and competition experiments showed that the uptake of ox-linoleate by Caco-2 cells is not saturable even at 150 microm and that this uptake is diluted in the presence of unox-linoleate. In esterification experiments utilizing rat intestinal microsomes, we show that both ox- and unox-linoleate are esterified equally well. In summary, dietary oxidized fatty acids can be absorbed by the intestine and incorporated into lipoproteins and could potentially impose an oxidative stress and exacerbate atherogenesis.

Acyltransferases↗
PubMed2000

The outcome and cost of alcohol and drug treatment in an HMO: day hospital versus traditional outpatient regimens.

OBJECTIVE: To compare outcome and cost-effectiveness of the two primary addiction treatment options, day hospitals (DH) and traditional outpatient programs (OP) in a managed care organization, in a population large enough to examine patient subgroups. DATA SOURCES: Interviews with new admissions to a large HMO's chemical dependency program in Sacramento, California between April 1994 and April 1996, with follow-up interviews eight months later. Computerized utilization and cost data were collected from 1993 to 1997. STUDY DESIGN: Design was a randomized control trial of adult patients entering the HMO's alcohol and drug treatment program (N = 668). To examine the generalizability of findings as well as self-selection factors, we also studied patients presenting during the same period who were unable or unwilling to be randomized (N = 405). Baseline interviews characterized type of substance use, addiction severity, psychiatric status, and motivation. Follow-up interviews were conducted at eight months following intake. Breathanalysis and urinalysis were conducted. Program costs were calculated. DATA COLLECTION: Interview data were merged with computerized utilization and cost data. PRINCIPAL FINDINGS: Among randomized subjects, both study arms showed significant improvement in all drug and alcohol measures. There were no differences overall in outcomes between DH and OP, but DH subjects with midlevel psychiatric severity had significantly better outcomes, particularly in regard to alcohol abstinence (OR = 2.4; 95% CI = 1.2, 4.9). The average treatment costs were $1,640 and $895 for DH and OP programs, respectively. In the midlevel psychiatric severity group, the cost of obtaining an additional person abstinent from alcohol in the DH cohort was approximately $5,464. Among the 405 self-selected subjects, DH was related to abstinence (OR = 2.1; 95% CI = 1.3, 3.5). CONCLUSIONS: Although significant benefits of the DH program were not found in the randomized study, DH treatment was associated with better outcomes in the self-selected group. However, for subjects with mid-level psychiatric severity in both the randomized and self-selected samples, the DH program produced higher rates of abstention and was more cost-effective. Self-selection in studies that randomize patients to services requiring very different levels of commitment may be important in interpreting findings for clinical practice.

Adult↗
PubMed1999

Role of sphingosine 1-phosphate in the mitogenesis induced by oxidized low density lipoprotein in smooth muscle cells via activation of sphingomyelinase, ceramidase, and sphingosine kinase.

Oxidized LDL (oxLDL) have been implicated in diverse biological events leading to the development of atherosclerotic lesions. We previously demonstrated that the proliferation of cultured vascular smooth muscle cells (SMC) induced by oxLDL is preceded by an increase in neutral sphingomyelinase activity, sphingomyelin turnover to ceramide, and stimulation of mitogen-activated protein kinases (Augé, N., Escargueil-Blanc, I., Lajoie-Mazenc, I., Suc, I., Andrieu-Abadie, N., Pieraggi, M. T., Chatelut, M., Thiers, J. C., Jaffrézou, J. P., Laurent, G., Levade, T., Nègre-Salvayre, A., and Salvayre, R. (1998) J. Biol. Chem. 273, 12893-12900). Since ceramide can be converted to other bioactive metabolites, such as the well established mitogen sphingosine 1-phosphate (S1P), we investigated whether additional ceramide metabolites are involved in the oxLDL-induced SMC proliferation. We report here that incubation of SMC with oxLDL increased the activities of both acidic and alkaline ceramidases as well as sphingosine kinase, and elevated cellular sphingosine and S1P. Furthermore, the mitogenic effect of oxLDL was inhibited by D-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol and N,N-dimethylsphingosine which are inhibitors of ceramidase and sphingosine kinase, respectively. These findings suggest that S1P is a key mediator of the mitogenic effect of oxLDL. In agreement with this conclusion, exogenous addition of sphingosine stimulated the proliferation of cultured SMC, and this effect was abrogated by dimethylsphingosine but not by fumonisin B1, an inhibitor of the acylation of sphingosine to ceramide. Exogenous S1P also promoted SMC proliferation. Altogether, these results strongly suggest that the mitogenic effect of oxLDL in SMC involves the combined activation of sphingomyelinase(s), ceramidase(s), and sphingosine kinase, resulting in the turnover of sphingomyelin to a number of sphingolipid metabolites, of which at least S1P is critical for mitogenesis.

Amidohydrolases↗
PubMed1999

15-Lipoxygenase catalytically consumes nitric oxide and impairs activation of guanylate cyclase.

Analysis of purified soybean and rabbit reticulocyte 15-lipoxygenase (15-LOX) and PA317 cells transfected with human 15-LOX revealed a rapid rate of linoleate-dependent nitric oxide (.NO) uptake that coincided with reversible inhibition of product ((13S)-hydroperoxyoctadecadienoic acid, or (13S)-HPODE) formation. No reaction of .NO (up to 2 microM) with either native (Ered) or ferric LOXs (0.2 microM) metal centers to form nitrosyl complexes occurred at these .NO concentrations. During HPODE-dependent activation of 15-LOX, there was consumption of 2 mol of .NO/mol of 15-LOX. Stopped flow fluorescence spectroscopy showed that.NO (2.2 microM) did not alter the rate or extent of (13S)-HPODE-induced tryptophan fluorescence quenching associated with 15-LOX activation. Additionally, .NO does not inhibit the anaerobic peroxidase activity of 15-LOX, inferring that the inhibitory actions of .NO are due to reaction with the enzyme-bound lipid peroxyl radical, rather than impairment of (13S)-HPODE-dependent enzyme activation. From this, a mechanism of 15-LOX inhibition by .NO is proposed whereby reaction of .NO with EredLOO. generates Ered and LOONO, which hydrolyzes to (13S)-HPODE and nitrite (NO2-). Reactivation of Ered, considerably slower than dioxygenase activity, is then required to complete the catalytic cycle and leads to a net inhibition of rates of (13S)-HPODE formation. This reaction of .NO with 15-LOX inhibited. NO-dependent activation of soluble guanylate cyclase and consequent cGMP production. Since accelerated .NO production, enhanced 15-LOX gene expression, and 15-LOX product formation occurs in diverse inflammatory conditions, these observations indicate that reactions of .NO with lipoxygenase peroxyl radical intermediates will result in modulation of both .NO bioavailability and rates of production of lipid signaling mediators.

Animals↗