• The Korean Journal of Zoology
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• v.38 no.4
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• pp.483-489
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• 1995

Retinoic acid was found to block membrane fusion of chick embryonic myoblasts in culture. This effed was dosedependent and could he reversed upon removal of the agent from the culture medium. Furthermore, the retinoic acid-mediated inhibition of membrane fusion was observed with the fusion competent cells but not with the cells that had already been committed for fusion, indicating that the effect of RA is differentiation stage-specific. However, retinoic acid showed little or no effect on the ability of the cells to form bipolar shape and to align along their axes. Neither the cell proliferation nor accumulation of muscle specific proteins, such as creatine kinase and tropomyosin, was impaired significantly. On the other hand, retinoic acid blocked the differentiation time~ependent loss of fibronectin, whose process is prerequisite for myoblast fusion. These results suggest that retinoic add acts as a specific inhibitor of membrane fusion by preventing the loss of fibronectin from the differentiating myoblasts.

• Journal of Life Science
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• v.21 no.4
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• pp.534-541
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• 2011

Retinoic acid (RA), a metabolite of vitamin A, is known to regulate dedifferentiation of rabbit articular chondrocytes. The regulatory mechanism of dedifferentiation by RA is not yet understood. Thus, the effect of RA on the regulation of nitric oxide (NO)-induced dedifferentiation was investigated in rabbit articular chondrocytes. RA caused loss of the differentiated chondrocyte phenotype as demonstrated by inhibition of type II collagen expression and proteoglycan synthesis. RA also accelerated NO-induced dedifferentiation in rabbit articular chondrocytes as detected by expression of type II collagen and Sox-9 using Western blot analysis and production of sulfated proteoglycan using Alcain blue staining. Further, RA potentiated NO-induced activation of ERK. Inhibition of ERK with PD98059 (PD) recovered the expression of type II collagen and Sox-9 and production of sulfate proteoglycan in NO-induced dedifferentiated chondrocytes by RA treatment. Our findings suggest that RA accelerates NO-induced dedifferentiation of rabbit articular chondrocytes via the ERK pathway.

• The Korean Journal of Zoology
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• v.37 no.4
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• pp.545-553
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• 1994

척추동물의 초기 발생에 관여하는 물질로 알려져 있는 retinoic acid(RA)를 Xenopus 배(embryo)에 처리한 결과, 체절의 형성에 이상 발생이 나타났다 즉 낭배 초기에 RA에 노출된 개체의 체절은 대조군의 화살머리 모양((((() 대신 기등 모양(1111)을 형성하고 있었으며, 고농도일수록 직선에 가까운 모습을 하고 있었다. 신경배 시기에 노출된 개체의 체절은 정상적인 분절이 이루어지지 않았으며, 이들 이상 체질의 위치는 처리 시기에 따라 다르게 나타났으나 농도에는 영향을 받지 않았다. 그러나 분절 과정중 일어나는 체절 세포들의 회전은 RA에 의해 억제되지 않았다. 이와 같은 결과는 체절의 형성에 분절 이전의 세포의 행동을 주도하는 프로그램과 분절을 주도하는 프로그램이 분리되어 있음을 암시한다. 한 가지 특이한 사항은 열처리 등으로 유발된 혼란이 수 개의 체절에 국한되어 나타나는 점과는 달리 RA의 처리는 어느 지점 이 후부터 모든 체절에 혼란을 야기시킨다는 점이다. 이와 같은 연속적인 분절의 흔란 현상은 RA가 다른 저해제에 의해 영향을 받는 유전자의 활동을 조절하는 전 단계의 유전자에 영향을 주기 때문인 것으로 사료된다. 또한 신경배 시기에 RA에 노출된 배의 a-cardiac actin은 정상적으로 발현되는데 비해 낭배 초기에 RA에 노출된 배는 감소된 양의 a-cardiac actin myNA의 축적을 보였다. 그러나 EFI-u은 RA의 처리 시기와는 무관하게 정상적으로 발현되었다.

• YAKHAK HOEJI
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• v.38 no.3
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• pp.230-237
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• 1994

The structure-activity relationships of (E)-chalcone-4-carboxylic acids, flavone-4'-carboxylic acids, two types of aromatic amides, terephthalic monoanilides, and (arylcarboxamido)benzoic acids, which were made by Shudo group, are discussed by conformation analysis(AM1) of retinoic acid and those compounds. Conformer of each compound is superimposed on the conformationally restricted compound, 4-(6,7,8,9-tetrahydro-6,6,9,9-tetramethyl-4H-4-oxonaphto[ 2,3-b]pyran-2-yl) benzoic acid(Fv80), possessing the strongest differentiation-inducing activity on human promyelocytic leukemia cells HL-60. The results indicated that the lengths between the carboxylic carbon and the two 6, 9 carbons binding to dimethyl, 1.20 nm and 1.09 nm, as well as the planarity of molecule are very important factors for the activity, especially 1.20 nm. In the case of the recently synthesized azulenic retinoic acids by Sato, et al. in 1993, the distance probably is also important, resulted from superimposing them on a Ch55 conformer and Fv80. The distance 1.0 nm is also important in Ch55. Several conformers of all-trans retinoic acid (RA) are well superimposed on the almost non-flexible Fv80, RA, 9-cis RA, and, specifically s-10,12 cis RA. And a simple hexangular model of RA is suggested to draw RA conformers easily without computer drawing model or molecular model.

• Journal of Animal Science and Technology
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• v.50 no.4
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• pp.475-484
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• 2008

The current study was undertaken to determine the effect of retinoic acid(RA) on differentiation and gene expression of pig preadipocytes. The preadipocytes were isolated from the backfat of the new-born pigs. RA was treated to the cultured cells for 4 days and RNA was extracted from the cells. Isolated RNA went through in situ hybridization using the 14,688-gene cDNA microarray chip. Degree of cell differentiation was determined by measuring glycerol 3-phosphate dehydrogenase activity. RA decreased differentiation of pig preadipocytes by 78%. Fourteen genes were significantly up-regulated by RA, including genes known to be involved in lipid metabolism, particulary sphingomyelin phosphodiesterase, apolipoprotein R precursor, growth factor receptor-bound protein 14, retinoic acid receptor RXR gamma. However, the expression of vascular endothelial growth factor D precursor and growth hormone receptor precursor genes playing a central role in cell growth, was greatly decreased. These results suggest that RA inhibits differentiation of pig preadiocytes by regulation of gene expression of the growth factor or growth hormone receptor.

• The Korean Journal of Zoology
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• v.33 no.3
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• pp.322-329
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• 1990

The effects of retinoic acid (RA) on the regenerating limbs of Korean newt (Hynobius leechii) larvae have been studied. Intraperitoneal injection of RA at 4 days post-amputation caused the proximalization of regenerate structures in the proximodistal (PD) axis of the limbs amputated through either the distal zeugopodium or the distal stylopodium. The mean level of proximalization (MLP) increased as a dose-dependent manner, and the MLP was also dependent on the level of amputation at a given dose of RA. At the dose of 150 $\mu$ g/g body wt., MLP's in either amputation level reached close to a peak value, and an increasing number of inhibition of regeneration or duplication in the transverse plane occurred at the dose of 200 $\mu$ g/ g body wt. and above. The changes induced by RA treatment suggest that positional values in the cells of the regenerating limbs have been modified in the three cardinal axes including PD and transverse axes in a graded mode. Furthermore, from the comparison of data in two different amputation levels, it can be speculated that the sensitivity of cells to RA effect along the PD axis might not be linear.

• BMB Reports
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• v.36 no.3
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• pp.265-268
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• 2003

Retinoic acid (RA) can transform the Golgi apparatus (GA) into a diffuse vacuolar aggregate and increase the toxicity of some immunotoxins that enter into cells by receptor-mediated endocytosis. An ultramorphological study of the RA-induced GA disruption was performed on F2000 fibroblasts. Cultures were treated with 0.11 to $30\;{\mu}M$ RA for 7 - 180 min. The endocytosis of Limax flavus agglutinin-peroxidase conjugate (LFA), and the interactions between a phorbol ester (PMA) and RA concerning GA disruption, were examined. Exposure to $0.33\;{\mu}M$ RA for 20 min transformed the GA into vacuolar aggregate. These vacuoles were not involved in endocytosis since they remained unstained after endocytosis of LFA. However, the lysosomes were involved in endocytosis, as they were strongly stained. Therefore, a RA-induced shift towards lysosomal routing of the entered LFA was presumed. Exposure to PMA made cells resistant to the Golgi-disturbing effects of RA, indicating that protein kinase C plays an important role in this process.

• 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.

• Biomolecules & Therapeutics
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• v.8 no.4
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• pp.285-292
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• 2000

The effects of the members of the same nuclear receptor superfamily (all-trans retinoic acid (RA), thyroid hormone(T3) or hydrocortisone) on proliferation and differentiation in the SK-N-SH neuroblastoma (NB) cell lines were studied. NB cells were treated with RA, T3, or hydrocortisone at concentration of 10$^{-6}$ M or 10$^{-8}$ M for 3 days or 7 days. RA induced concentration- and time-dependent morphologic differentiation(neurite outgrowth and microtubule-associated protein expression) and growth inhibition in NB cells. Treatment of 10$^{-7}$ M T3 for 7 days increased viability and differentiation of NB cells. Treatment of 10$^{-6}$ M hydrocortisone for 7 days increased viability of NB cells. Although these three effectors are members of the same receptor superfamily, the regulation of brain development may be carried out in a different manner.

• Animal cells and systems
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• v.6 no.4
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• pp.301-304
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• 2002

In our previous study, we have shown that Fgf-8 is expressed in the basal layer of the apical epithelial cap (AEC) and in the underlying thin layer of mesenchymal tissue of the regenerating limbs of Mexican axolotl, Amby-stoma mexicanum. Our present RT-PCR data also demonstrate that Fgf-8 transcript is localized both in the mesenchymal and epidermal tissues. To understand the effect of retinoic acid (RA) on the expression of Fgf-8 in the regenerating axolotl limbs, RA was injected intraperitoneally at the dediffer-entiation stage of limb regeneration. The RA treatment caused 8 change in the Fgf-8 expression profile of the regenerating limbs. In RA-treated limbs, duration of Fgf-8 expression was prolonged and a high level of expression was maintained during dedifferentiation and blastema formation stages. These results suggest that Fgf-8 is an important molecule in the process of pattern duplication of regenerating salamander limbs evoked by RA treatment.