• Archives of Pharmacal Research
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• v.20 no.2
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• pp.115-121
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• 1997

Ile-269 in horse liver alcohol dehydrogenase isoenzyme S(HLADH-S) was mutated to serine by phosphorothioate-based site-directed mutagenesis in order to study the role of the residue in coenzyme binding. The specific activity of the mutant(1269S) enzyme to ethanol was increased 49-fold. All turnover numbers of 1269S enzyme toward 9 primary alcohols were increased. The mutant enzyme showed 3.6, 4.6, 11.6-fold higher catalytic efficiency for $5{\beta}$-androstane-3, 17-dione, $5{\beta}$-cholanic acid-3-one and retinal than wild-type, respectively. The reaction mechanism of 1269S enzyme was ordered bi bi as wild-type's. These results indicate that the hydrophobic interaction of Ile-269 residue with coenzyme plays an important role in dissociation of coenzyme from enzyme-coenzyme complex, which has been known as the rate limiting step of ADH reaction.

• Journal of Nutrition and Health
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• v.24 no.3
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• pp.199-205
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• 1991

Retinoic acid. the active metabolite of vitamin A. was detected in the human liver for the first time using a new method. A rapid and sensitive technique has been developed using gradient-elution. reverse-phase high performance liquid chromatography. This assay. with simultaneous multiwavelength detection at 294nm, 325nm and 450nm after saponifcation of liver samples. allows us seperation and quantitation of vitamin E, retinoic acid, total retinoids and various carotenoids in one small sample. The proportion of retinoic acid to total retinoids in human liver appears to be quite $consistent(2.4\pm0.2%$ ). With low vitamin A storage in liver, detection at another wavelenth 354nm would increase the sensitivity for retinoic acid of small quantity This method of analysis could be used for other tissues like red blood cells, plasma or serum, also. Hepatic retinoic acid level with total retinoids and carotenoids would serve a better indicator of functional vitamin A nutriture especially for those with disease requiring needle biopsy of liver.

• The Korean Journal of Pharmacology
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• v.18 no.1
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• pp.65-72
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• 1982

It has been known that retinoids are intrinsically of critical importance for control of premalignant epithelial cell differentiation. In the absence of retinoids, normal cellular differentiation and growth does not occur in epithelia such as those of trachea and bronchi. Furthermore, it was also reported that retinoid deficiency enhanced susceptibility to chemical carcinogenesis in the respiratory system, in the bladder, and in the colon of the experimental animal. In 1974, Bollag examined the effects of synthetic retinoids in prevention of development of cancer and demonstrated synthetic retinoids to have more favorable therapeutic index than retinoic acid for causing regression of skin papilloma in mice. Therefore, it was assumed that this anticarcinogenic effect of vitamin A derivatives could be due to modification of the metabolism of the carcinogenic polycyclic hydrocarbon, which must first be activated to exert their effect. Hill and Shih reported that vitamin A compounds and analogs had inhibitory effect on drug metabolizing enzyme from liver and lung tissue of mouse and hamster. Lucy suggested that the chemoprevention effect of vitamin A derivatives is due to reaction with molecular oxygen, and it is possible that inhibition of hydroxybenzpyrene formation is a result of this property. On the other hand, butylated hydroxytoluene which is a potent antioxidant strongly inhibited the formation of mammary tumor induced by dimethylbenranthracene. Also, it was observed that this antioxidant inhibited cancer induction in rats by N-2-fluo-renylacetamide. The purpose of this experiment was to investigate the effect of vitamin A derivatives such as retinoic acid and retinoid on drug-metabolizing enzyme and to determine whether riboflavin tetrabutylate or vitamin E could prevent of modify any changes induced by vitamin A delivatives in the rats. The results obtained were as followings. 1) Body weight was significantly reduced by retinoic acid, but not by retinoid. 2) Retinoic acid markedly increased liver weight while retincid showed no effect on liver weight. Treatment of riboflavin tetrabutylate did not affect retinoic acid-induced change in both body weight and liver weight. 3) Both retinoic acid and retinoid remarkably decreased the activity of aminopyrine demethylase. Pretreatment of riboflavin tetrabutylate, however, prevented inhibitory effect of retinoic acid on the enzyme activity. 4) No significant effect of vitamin E on aminopyrine demethylase was observed in both groups treated with retinoic acid and retinoid.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.05a
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• pp.91-91
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• 2002

• Journal of the Korean Medical Association
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• v.61 no.11
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• pp.680-686
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• 2018

Acne vulgaris is a very common condition affecting up of about 80% to 90% of adolescents. The patients with acne have been shown to be adversely impacted by the effect of acne on their quality of life. Four factors are believed to play a key role in the development of acne lesions: excess sebum production, disturbed keratinization within the follicle, colonization of the pilosebaceous duct by Propionibacterium acnes, and the release of inflammatory mediators into the skin. Consequently, the target for acne therapy is these well-known pathogenic factors responsible for this disease state. Topical retinoids correct abnormal keratinization, but it should be applied cautiously because of irritation. Benzoyl peroxide is an effective bactericidal agent against P. acnes. Main topical antibiotics are erythromycin and clindamycin. Fixed combination topical products with retinoids, benzoyl peroxide and antibiotics have been introduced. Use of systemic antibiotics, including tetracyclines and macrolides rapidly improves inflammatory acne lesions. Oral isotretinoin is effective against all of the main pathogenic features of acne but is contraindicated in pregnant women and has been associated with cheilitis and dry skin. Hormonal therapy has been found to improve acne in some selective patients and should be considered for appropriate candidates. This review will present the general aspects of the pharmacological treatments for acne.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.36 no.6
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• pp.481-489
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• 2010

Introduction: TLR-5, a member of the toll-like receptor (TLR) family, is a element of the type I transmembrane receptors, which are characterized by an intracellular signaling domain homolog to the interleukin-1 receptor. These receptors recognize microbial components, particularly bacterial flagellin. All-trans retinoic acid (atRA, tretinoin), a natural metabolite of vitamin A, acts as a growth and differentiation factor in many tissues, and is also needed for immune functions. In this study, THP-1 human macrophage-monocytes were used to examine the mechanisms by which atRA regulated the expression of TLR-5. Because the molecular mechanism underlying this regulation at the transcriptional level is also unclear, this study examined which putative transcription factors are responsible for TLR-5 expression by atRA in immune cells. Materials and Methods: This study examined whether atRA induces the expression of TLR-5 in THP-1 cells using reverse transcription-polymerase chain reaction (RT-PCR), and which transcription factors are involved in regulating the TLR-5 promoter in RAW264.7 cells using a reporter assay system. Western blot analysis was used to determine which signal pathway is involved in the expression of TLR-5 in atRA-treated THP-1 cells. Results: atRA at a concentration of 10 nM greatly induced the expression of TLR-5 in THP-1 cells. Human TLR-5 promoter contains three Sp-1/GC binding sites around -50 bp and two NF-kB binding sites at -380 bp and -160 bp from the transcriptional start site of the TLR-5 gene. Sp-1/GC is primarily responsible for the constitutive TLR-5 expression, and may also contribute to NF-kB at -160 bp to induce TLR-5 after atRA stimulation in THP-1 cells. The role of NF-kB in TLR-5 expression was further confirmed by inhibitor pyrrolidine dithiocarbamate (PDTC) experiments, which greatly reduced the TLR-5 transcription by 70-80%. Conclusion: atRA induces the expression of the human TLR-5 gene and NF-kB is a critical transcription factor for the atRA-induced expression of TLR-5. Accordingly, it is conceivable that retinoids are required for adequate innate and adaptive immune responses to agents of infectious diseases. atRA and various synthetic retinoids have been used therapeutically in human diseases, such as leukemia and other cancers due to the antiproliferative and apoptosis inducing effects of retinoids. Therefore, understanding the molecular regulatory mechanism of TLR-5 may assist in the design of alternative strategies for the treatment of infectious diseases, leukemia and cancers.

• Toxicological Research
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• v.7 no.2
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• pp.209-229
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• 1991

In the epidermis of skin, a fine balance exists between proliferating progenitor cells and terminally differentiating cells. We examined the effects of TGF-betas and retinoic acid (RA) on controlling this balance in normal human epidermal keratinocytes cultured under conditions where most morphological and biochemical features of epidermis in vivo are retained. Our results revealed marked and pleiotropic effects of both TGF-beta and RA on kerationcytes. In contrast to retinoids, TGF-betas acted on mitotically active basal cells to retard cell proliferation.

• Polymer(Korea)
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• v.26 no.6
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• pp.710-717
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• 2002

Molecularly imprinted polymers were prepared in particle forms by crosslinking methacrylic acid (MAA)) using all trans-retinoic acid as a template. The HPLC column packed with the prepared molecular imprinted polymers showed high capability in separation of retinoid derivatives. The column capacity factor and selectivity increased with increasing MAA to template ratio when the incorporated template amount was fixed, as it statistically generated more binding sites between host molecules and template. Molecularly imprinted polymer particles prepared via an emulsion polymerization method were round-shaped and their sizes were more uniformly distributed, but their separation capability was inferior to those obtained by solution polymerization method. It was presumably because the loss of interaction strength between MAA and the template due to hydrogen bonding either between MAA and water or between template and water during the synthesis of molecularly imprinted polymers.

• Tuberculosis and Respiratory Diseases
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• v.44 no.1
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• pp.162-174
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• 1997

Background : Metabolic cooperation via gap junctional intercellular communication (GJIC) is an important mechanism of the bystander effect in gene therapy using the Herpes Simplex Virus thymidine kinase/ganciclovir (HSVtk) "prodrug" system. Since retinoids have been reported to increase GJIC by induction of connexin 43 expression, we hyporthesized that treatment of tumor cells with retinoic acid could augment the bystander effect of the HSVtk/GCV system and result in improved tumor cell killing by enhancing GJIC. Methods : We transferred HSVtk gene to SKHep-J cell line that does not express connexin43, and also transferred the gene to human and murine mesothelioma cell lines that express connexin43. We verified that retinoic acid enhanced GJIC utilizing a functional double-dye transfer study and evaluated the effects of retinoic acid on the growth rate of tumor cells. We then tested the effects of retinoic acid on bystander-mediated cell killing. Results : Addition of all-trans retinoic acid (RA) increased GJIC in cell lines expressing connexin 43 and was asspciated with more efficient in vitro bystander killing in cells transduced with HSVtk via adenoviral and retroviral vectors. In contrast, there was no increase in the efficiency of the bystander effect after exposure to RA in a cell line which had no delectable connexin 43. Conclusion : These results provide evidence that retinoids can augment the efficiency of cell killing with the HSVtk/GCV system by enhancing bystander effect and may thus be a promising new approach to improve responses in gene therapy utilizing the HSVtk system to treat tumors.

• Tuberculosis and Respiratory Diseases
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• v.80 no.1
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• pp.1-10
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• 2017

Chronic obstructive pulmonary disease (COPD) is a critical condition with high morbidity and mortality. Although several medications are available, there are no definite treatments. However, recent advances in the understanding of stem and progenitor cells in the lung, and molecular changes during re-alveolization after pneumonectomy, have made it possible to envisage the regeneration of damaged lungs. With this background, numerous studies of stem cells and various stimulatory molecules have been undertaken, to try and regenerate destroyed lungs in animal models of COPD. Both the cell and drug therapies show promising results. However, in contrast to the successes in laboratories, no clinical trials have exhibited satisfactory efficacy, although they were generally safe and tolerable. In this article, we review the previous experimental and clinical trials, and summarize the recent advances in lung regeneration therapy for COPD. Furthermore, we discuss the current limitations and future perspectives of this emerging field.