• BMB Reports
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• v.35 no.5
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• pp.518-523
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• 2002

Nordihydroguaiaretic acid (NDGA), an inhibitor of lipoxygenase, inhibits the secretion of proteins and causes the redistribution of resident Golgi proteins into the endoplasmic reticulum (ER). In this study, the effect of NDGA on lipoprotein lipase (LPL) secretion was investigated in 3T3-L1 adipocytes, and compared with those of brefeldin A (BFA), a well-known fungal metabolite that exhibits similar ER-Golgi redistribution. Both BFA and NDGA blocked secretions of LPL. In the presence of BFA, the active and dimeric LPL was accumulated in adipocytes. After endoglycosidase H (endo H) digestion, the proportion of LPL subunits with partially endo H-sensitive oligosaccharide was significantly increased with BFA. However, in the presence of NDGA, the cellular LPL became inactive, and only the endo H-sensitive fraction of the LPL subunit was observed. An increase of the aggregated forms was observed in the fractions of the sucrose-density gradient ultracentrifugation. These properties of LPL in the NDGA-treated cells were similar to those of LPL that is retained in ER, and the effects of NDGA could not be reversed by BFA. These results indicate that the inhibitory mechanism of NDGA on the LPL secretion is functionally different from the ER-Golgi redistribution that is induced by BFA.

• The Korean Journal of Pharmacology
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• v.29 no.2
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• pp.237-244
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• 1993

The effect of nicotine on the secretion of $[Met^{5}]-enkephalin$ (ME) in addition to proenkephalin A (proENK) mRNA levels and effects of indomethacin, nordihydroguaiaretic acid (NDGA), and captopril on nicotine-induced responses were studied in bovine adrenal medullary chromaffrin (BAMC) cells. Long-term exposure of BAMC cells to nicotine at a concentration of $10{\mu}M$ significantly increased proENK mRNA level and the secretion of ME into the medium. Treatment of BAMC cells with NDGA (a lipoxygenase inhibitor, $10{\mu}M$), indomethacin (a cycloooxygenase inhibitor) or captopril (an angiotensin converting enzyme inhibitor) alone did not affect ME secretion and proENK mRNA levels. The pretreatment of BAMC cells with NDGA inhibited the increased ME secretion and proENK mRNA level induced by nicotine. However, indomethacin and captopril did not affect nicotine-induced responses. Our results indicate that neuronal regulations of ME secretion and proENK mRNA level induced by nicotine in BAMC cells are in part mediated by a lipoxygenase-but not cyclooxygenase-and endogenous renin-angiotensin pathway.

• Biomolecules & Therapeutics
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• v.20 no.5
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• pp.463-469
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• 2012

Atopic dermatitis is a chronic, inflammatory disease of the skin with increased transepidermal water loss. Both an abnormal inflammatory response and a defective skin barrier are known to be involved in the pathogenesis of atopic dermatitis. Protease activated receptor 2 (PAR2) belongs to a family of G-protein coupled receptors and is activated by both trypsin and a specific agonist peptide, SLIGKV-$NH_2$. PAR2 is expressed in suprabasal layers of the epidermis and regulates inflammatory responses and barrier homeostasis. In this study, we show that nordihydroguaiaretic acid (NDGA) inhibits the PAR2-mediated signal pathway and plays a role in skin barrier recovery in atopic dermatitis. Specifically, NDGA reduces the mobilization of intracellular $Ca^{2+}$ in HaCaT keratinocytes by down-regulating inflammatory mediators, such as interleukin-8, thymus and activation-regulated chemokine and intercellular cell adhesion molecule-1 in HaCaT keratinocytes. Also, NDGA decreases the protein expression of involucrin, a differentiation maker of keratinocyte, in both HaCaT keratinocytes and normal human epidermal keratinocytes. We examined NDGA-recovered skin barrier in atopic dermatitis by using an oxazolone-induced atopic dermatitis model in hairless mice. Topical application of NDGA produced an increase in transepidermal water loss recovery and a decrease in serum IgE level, without weight loss. Accordingly, we suggest that NDGA acts as a PAR2 antagonist and may be a possible therapeutic agent for atopic dermatitis.

• YAKHAK HOEJI
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• v.33 no.1
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• pp.1-9
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• 1989

We have recently reported that $Mg^{++}-deficiency$ showed endothelium dependent relaxation in isolated canine coronary arteries precontracted with $PGF_{2{\alpha}}$. To differentiate the release of EDRF or $PGI_2$ from the endothelium cells as the cause of vasorelaxation by $Mg^{++}-deficiency$, effects of several inhibitors of arachidonic acid metabolism on the relaxation by $Mg^{++}-deficiency$ were evaluated and also compared with that of acetylcholine. Ibuprofen and tranylcypromine ($10{\mu}M$), an inhibitor of cyclo-oxygenase and $PGI_2$ synthetase, respectively, did not effect on $Mg^{++}-free$ induced vasorelaxation. Pretreatment of quinacrine ($10{\mu}M$), an inhibitor of phospholipase $A_2$ and also $Ca^{++}$ uptake, blocked vasorelaxation by $Mg^{++}-free$. But trifluoperazine ($10{\mu}M$), which is about as potent as quinacrine in the inhibition of $Ca^{++}$ uptake, did not effect on $Mg^{++}-deficiency$ induced vasorelaxation. NDGA ($10{\mu}M$), an inhibitor of lipoxygenase, completely restored $Mg^{++}-free$ induced vasorelaxation, even though pretreatment of that was not blocked which might be due to the characteristics of vasorelaxation of NDGA itself. Pretreatment of methylene blue ($10{\mu}M$), which is known as a inhibitor of EDRF through the blocking effect of guanylate cyclase, completely blocked vasorelaxation by $Mg^{++}-free$ as well as acetylcholine ($0.1{\mu}M$). Acetylcholine-induced dose response curve was also antagonized by pretreatment of quinacrine ($10{\mu}M$), but not by ibuprofen, tranylcypromine and NDGA. These results appear to suggest that $Mg^{++}-free$ induced vasorelaxation was mediated by the release of EDRF through the activation of phospholipase $A_2$ and noncyclo-oxygenase on arachidonate metabolism.

• Bulletin of the Korean Chemical Society
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• v.26 no.7
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• pp.1117-1120
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• 2005

• Archives of Pharmacal Research
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• v.21 no.6
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• pp.664-670
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• 1998

The role of intracellular $Ca^{2+}$, in the regulation of tumor cell proliferation by products of arachidonic acid (AA) metabolism was investigated using U-373 MG human as trocytoma cells. Treatment with nordihydroguaiaretic acid (NDGA), a lipoxygenase (LOX) inhibitor, or caffeic acid (CA), a specific 5-LOX inhibitor, suppressed proliferation of the tumor cells in a dose-dependent manner. However, indomethacin (indo), a cyclooxygenase (COX) inhibitor, did not significantly alter proliferation of the tumor cells. At anti-proliferative concentrations, NDGA and CA significantly inhibited intracellular $Ca^{2+}$ release induced by carbachol, a known intracelluar $Ca^{2+}$ agonist in the tumor cells. Exogenous administration of leukotriene $B_4(LTB_4)$, an AA metabolite of LOX pathway, enhanced proliferation of the tumor cells in a concentration-dependent fashion. In addition, $LTB_4$, induced intracelluar $Ca^{2+}$ release. Intracellular $Ca^{2+}$-inhibitors, such as an intracellular $Ca^{2+}$ chelator (BAPTA) and intracellular $Ca^{2+}$-release inhibitors (dantrolene and TMB-8), significantly blocked the LTB4-induced enhancement of cell proliferation and intracellular $Ca^{2+}$ release. These results suggest that LOX activity may be critical for cell proliferation of the human astrocytoma cells and that intracelluar $Ca^{2+}$ may play a major role in the mechanism of action of LOX.

• Journal of Korean Neurosurgical Society
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• v.29 no.1
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• pp.28-34
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• 2000

Object : To verify the effect of the lipoxygenase inhibitor and cycloxygenase inhibitor on meningioma cell proliferation. Method : Using two meningioma cell lines, cell proliferation was determined at 96 hrs after adding inhibitor (AA861, Nordihydroguaiaretic acid(NDGA), Indomethacin, acetyl-11-keto-beta-boswellic acid(AKBA) into medium by methyl tetrazolium salt/phenazine methosulfate(MTS/PMS) non-radioactive cell proliferation assay. We checked optical density with 490nm wavelength UV and this value was used as a proliferative index. The percent of inhibition was also calculated from this value. Conclusion : Indomethacin and NDGA showed no effect on meningioma proliferation. AA861 also showed no significant inhibitory effect, but AKBA demonstrated a significant inhibitory effect on meningioma cell proliferation.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.8 no.4
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• pp.213-216
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• 1975

Yellow sea bream contains comparatively larger amount of fat among white muscle fishes, so that rancidity might easily occur during drying and storage. For the purpose of the protection of rancidity, the effect of some antioxidants was studied when yellow sea bream was sun-dried after dipping in the solutions and packed in PVC film$0.3mm\times12cm\times30cm $ for storage at room temperature. The inhibitory effect of additives was in order of Tenox-II, BHA, Sustane and NDGA, while EDTA, potassium sorbate, CTC and $\alpha-naphthylamine$ were ineffective. The results suggest that the treatment of $0.1\%$ Tenox-II solution and packing in PVC film is better condition to improve the quality of product and during drying and storage.

• Journal of the Korean Society of Food Science and Nutrition
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• v.17 no.1
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• pp.19-23
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• 1988

The natural antioxidants such as ${\alpha}-tocopherol$, NDGA, proply gallate and sesamol, and synthetic antioxidants, BHA were used to compare antioxidative effects of those antioxidants from tile physico-chemical properties and fatty acid composition changes in the soybean oil during storage. The oils were stored at $25^{\circ}C$ for 2 weeks after heat treatment. Natural antioxidants were less effective than BHA but effect of ${\alpha}-tocopherol$ was very similar to that of BHA. The order of antioxidative effect was BHA, ${\alpha}-tocopherol$, NDCA propyl gallate and sesamol. The relative contents of linoleic acid and linolenic acid was decreased as the degree of oxidative rancidity was increased. whereas content of oleic acid and palmitic acid was increased. The content of linoleic acid and linolenic acid did not decreased by addition of BHA and ${\alpha}-tocopherol$.

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