• The Korean Journal of Pharmacology
• /
• v.28 no.2
• /
• pp.163-170
• /
• 1992

The present study was attempted to investigate the effect of cyclobuxine (a steroidal alkaloid) on generation of reactive oxygen metablite and myocardial damage promoted by an exogenous administeration of arachidonate in ischemic-reperfused hearts. Langendorff preparation of the isolated rat heart was made ischemic condition by reducing the flow rate to 0.5 ml/min for 45 min, and then followed by normal reperfusion (7 ml/min) for 5 min. The generation of superoxide anion was estimated by measuring the SOD-inhibitable ferricytochrome C reduction. The degree of lipid peroxidation in myocardial tissue was estimated from the tissue malondialdehyde (MDA) concentration using thiobarbituric acid method. The myocardial cell damage was observed by measuring LDH released into the coronary effluent. Sodium arachidonate $(0.1\;and\;1.0\;{\mu}g/ml)$ infused during the period of oxygenated reperfusion stimulated superoxide anion production dose-dependently. The rate of arachidonate-induced superoxide anion generation was markedly inhibited by cyclobuxine $(1.0\;and\;10\;{\mu}g/ml)$. The production of malondialdehyde was increased by infusion of arachidonate. This increase was prevented by superoxide dismutase (300 U/ml) and cyclobuxine $(1.0\;and\;10\;{\mu}g/ml)$. The release of LDH was increased by sodium arachidonate was also inhibited by superoxide dismutase and cyclobuxine. In conclusion, the present results suggest that cyclobuxine inhibits the production of reactive oxygen metabolite and myocardial damages which were promoted by an administeration of arachidonate during reperfusion of ischemic hearts.

• Proceedings of the KSAR Conference
• /
• 2000.10a
• /
• pp.3-4
• /
• 2000

The synthesis of acyl-CoA catalyzed by acyl-CoA synthetase (ACS, EC 6.2.1.3) from fatty acid, ATP, and CoA is a crucial reaction in mammalian fatty acid metabolism. In arachidonate metabolism, acyl-CoA synthetase(ACS) plays a key role in the esterification of free arachidonate into membrane phospholipids. Following its release by the action of calcium dependent phospholipase, free arachidonate is believed to be rapidly converted to arachidonoyl-CoA and reesterified into phospholipids in order to prevent excessive synthesis of eicosanoids. In previous studies, we have characterized five ACSs (designated as ACS1-5) with different tissue distribution. ACS1, ACS2, and ACS5 are similar in structure and fatty acid preference, and completely different from ACS3 and ACS4. The latter are arachidonate-preferring enzymes closely related in structure but expressed in different tissues: ACS3 mRNA is highly expressed in the brain and the mRNA for ACS4 is expressed in steroidogenic tissues including adrenal gland, ovary, and testis. To learn more about the potential function of ACS4 in arachidonate metabolism, we have produced knock-out mice for ACS4 gene. ACS4+/- females become pregnant less frequently and produce small litters with extremely low transmission of the disrupted alleles. Striking morphological changes including extremely enlarged uterine filled with numerous proliferative cysts of various size were detected in ACS4+/- females. Furthermore, marked accumulation of prostaglandins were seen in the uterus of heterozygous females. These results indicate that ACS4 is critical for the uterine arachidonate metabolism and heterozygous disruption of its gene lead to impaired pregnancy.

• Environmental Analysis Health and Toxicology
• /
• v.8 no.3_4
• /
• pp.1-5
• /
• 1993

Using mixed incubation of cultured endothelial cells, cultured fibroblasts, neutrophils activated with PMA and paraquat, the production of superoxide anion, $H_2O$$_2$and lipoxygenase metabolites (5-HETE and 12-HETE) of arachidonate was estimated. The results was as follows: 1. Neutrophils activated with PMA was produced superoxide anion,$H_2O_2$and lipoxygenase metabolites (5-HETE and 12-HETE) of arachidonate. 2. Fibroblasts did not alter the production of superoxide anion and $H_2O_2$ by neutrophils, it was markedly reduced by mixed incubation with endothelial cells. 3. Mixed incubation with endothelial cells significantly augmented the production of 5 or 12-HETEs, but fibroblasts did not. 4. Using mixed incubation of endothelial cells, fibroblasts, neutrophils and paraquat (50ug/m1 and 100ug/m1), the production of superoxide anion, $H_2O_2$and HETEs was significantly increased on both cells at low concentration (50ug/m1), but markedly reduced at high concentration (1001g/m1). 5. Paraquat showed concentration dependent effects on arachidonate lipoxygenase metabolism.

• Proceedings of the KSAR Conference
• /
• 2004.06a
• /
• pp.225-225
• /
• 2004

Acyl-CoA synthetase 4(ACS4) is an arachidonate-preferring enzyme aboundant in steroidogenic tissues and postulated to modulate eicosanoid production. Most of arachidonate present in cells is esterified predominantly in phospholipids. After its release by the action of calcium-dependent phospholipases, arachidonate can be converted to prostaglandins, thromboxanes, and leukotrenes via the cyclooxygenas and lipoxygenase pathways, respectively, depending on the cell type.(omitted)

• Korean Journal of Veterinary Research
• /
• v.28 no.2
• /
• pp.311-319
• /
• 1988

This study was designed to elucidate the effects of iron, a well known catalyst of lipid peroxidation, on the contents of phospholipids, unsaturated fatty acids composed in phospholipid molecules and their derivatives, prostaglandins, and the composition changes of fatty acids contained in phospholipids. Iron decreased the contents of phospholipids and its components of unsaturated fatty acids. Catalytic action of iron decreased the composition rates of linoleate and linolenate composed in phospholipid molecules, while that of arachidonate was inclined to increase. The content of arachidonate was increased and that of prostaglandins was decreased without regard to increase the precursor of prostaglandins. It may be concluded that the decreases of prostaglandins and the increase of arachidonate are due to inhibition of the activities of enzyme systems responsible for prostaglandin synthesis by lipid peroxides produced by the catalyst of iron.

• Archives of Pharmacal Research
• /
• v.20 no.6
• /
• pp.533-538
• /
• 1997

Biflavonoid is one of unique classes of naturally-occurring bioflavonoid. Previously, certain biflavonoids were found to possess the inhibitory effects on phospholipase $A_2$ activity and lymphocytes $ proliferation^1$ suggesting their anti-inflammatory/immunoregulatory potential. In this study, effects of several biflavonoids on arachidonic acid release from rat peritoneal macrophages were investigated, because arachidonic acid released from the activated macrophages is one of the indices of inflammatory conditions. When resident peritoneal macrophages labeled with $[^{3}H]$arachidonic acid were activated by phorbol 12-myristate 13-acetate(PMA) or calcium ionophore, A23187, radioactivity released in the medium was increased approximately 4.1-7.3 fold after 120 min incubation compared to the spontaneous release in the control incubation. In this condition, biflavonoids (10 uM) such as ochnaflavone, ginkgetin and isoginkgetin, showed inhibition of arachidonate release from macrophages activated by PMA (32.5-40.0% inhibition) or A23187 (21.7-41.7% inhibition). Amentoflavone showed protection only against PMA-induced arachidonate release, while apigenin, a monomer of these biflavonoids, did not show the significant inhibition up to 10 uM. Staurosporin (1 uM), a protein kinase C inhibitor, showed an inhibitory effect only against PMA-induced arachidonate release (96.8% inhibition). Inhibition of arachidonate release from the activated macrophages may contribute to an anti-inflammatory potential of biflavonoids in vivo.

• The Korean Journal of Pharmacology
• /
• v.27 no.2
• /
• pp.109-118
• /
• 1991

The present study was conducted to assess the possible contribution of arachidonic acid to generation of reactive oxygen metabolites and myocardial damage in ischemic-reperfused heart. Langendorff preparations of isolated rat heart were made ischemic by hypoperfusion (0.5 ml/min) for 45 min, and then followed by normal oxygenated reperfusion (7 ml/min). The generation of superoxide anion was estimated by measuring the SOD-inhibitable ferricytochrome C reduction. The myocardial cellular damage was observed by measuring LDH released into the coronary effluent. Oxygenated reperfusion following a period of ischemia produced superoxide anion, which was inhibited by both indomethacin (60 nmole/ml) and ibuprofen $(30\;{\mu}g/ml)$. Sodium arachidonate $(10^{-7}-10^{-2}{\mu}g/ml)$ administered during the period of oxygenated reperfusion stimulated superoxide anion production dose-dependently. The rate of arachidonate-induced superoxide generation was markedly inhibited by indomethacin, a cyclooxygenase inhibitor; nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, and by eicosatetraynoic acid (ETYA), a substrate inhibitor of arachidonic acid metabolism. The release of LDH was increased by Na arachidonate and was inhibited by superoxide dismutase. The release of LDH induced by arachidonic acid was also inhibited by indomethacin, NDGA and ETYA. In conclusion, the present result suggests that arachidonic acid metabolism is involved in the production of reactive oxygen metabolite and plays a contributory role in the genesis of reperfusion injuy of myocardium.

• Biomolecules & Therapeutics
• /
• v.14 no.4
• /
• pp.216-219
• /
• 2006

In order to establish the anti-inflammatory cellular mechanism of the paeony root(Paeonia lactiflora, Pall, Paeoniaceae), the constituents including paeoniflorin, albiflorin, (+)-catechin, paeonol, benzoic acid and methyl gallate were evaluated for their effects on arachidonate and NO metabolism. Among the compounds tested, only paeonol weakly inhibited cyclooxygenase-2-mediated $PGE_2$ production from LPS-treated RAW 264.7 cells. (+)-Catechin and methyl gallate weakly inhibited inducible nitric oxide synthase-mediated NO production from the same cell line. In particular, methyl gallate significantly inhibited 5-lipoxygenase from RBL-l cells with an $IC_{50}$ of 8.4 ${\mu}M$. These results suggest that the inhibition of these components on arachidonate and NO metabolism may contribute at least in part to anti-inflammatory mechanism of the paeony root.

• The Korea Genome Conference
• /
• 2006.09a
• /
• pp.60-60
• /
• 2006

• Proceedings of the PSK Conference
• /
• 2003.04a
• /
• pp.111-113
• /
• 2003

Biosynthsis of prostaglandin E2 (PGE2), the most common prostanoid with potent and diverse bio-activities, is regulated by three sequential enzymatic steps composed of phospholipase A2, cyclooxygenase (COX), and prostaglandin E synthase (PGES). Recently, three distinct PGESs have been identified; two of them are membrane-bound enzymes, mPGES-1 and mPGES-2, and the third one is a cytosolic enzyme, cPGES. (omitted)