• BMB Reports
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• v.56 no.2
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• pp.84-89
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• 2023

The implications of nutrient starvation due to aging on the degeneration of the retinal pigment epithelium (RPE) is yet to be fully explored. We examined the involvement of AMPK activation in mitochondrial homeostasis and its relationship with the maintenance of a healthy mitochondrial population and epithelial characteristics of RPE cells under nutrient starvation. Nutrient starvation induced mitochondrial senescence, which led to the accumulation of reactive oxygen species (ROS) in RPE cells. As nutrient starvation persisted, RPE cells underwent pathological epithelial-mesenchymal transition (EMT) via the upregulation of TWIST1, a transcription regulator which is activated by ROS-induced NF-κB signaling. Enhanced activation of AMPK with metformin decelerated mitochondrial senescence and EMT progression through mitochondrial biogenesis, primed by activation of PGC1-α. Thus, by facilitating mitochondrial biogenesis, AMPK protects RPE cells from the loss of epithelial integrity due to the accumulation of ROS in senescent mitochondria under nutrient starvation.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.3
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• pp.231-240
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• 2023

Fabry disease is a lysosomal storage disorder characterized by the lysosomal accumulations of glycosphingolipids in a variety of cytotypes, which include endothelial cells. The disease is inherited and originates from an error in glycosphingolipid catabolism caused by insufficient α-galactosidase A activity, which causes uncontrolled progressive storage of intracellular globotriaosylceramide (Gb3) in the vasculature and extracellular accumulation of lyso-Gb3 (a deacetylated soluble form of Gb3). Necrosis can lead to inflammation, which exacerbates necrosis and creates a positive feedback loop that triggers necroinflammation. However, the role played by necroptosis, a form of programmed necrotic cell death, in the cell-to-cell inflammatory reaction between epithelial and endothelial cells is unclear. Thus, the present study was undertaken to determine whether lyso-Gb3 induces necroptosis and whether necroptosis inhibition protects endothelial dysfunction against lyso-Gb3 inflamed retinal pigment epithelial cells. We found lyso-Gb3 induced necroptosis of a retinal pigment epithelial cell line (ARPE-19) in an autophagy-dependent manner and that conditioned media (CM) from ARPE-19 cells treated with lyso-Gb3 induced the necroptosis, inflammation, and senescence of human umbilical vein endothelial cells. In addition, a pharmacological study showed CM from lyso-Gb3 treated ARPE-19 cells induced endothelial necroptosis, inflammation, and senescence were significantly inhibited by an autophagy inhibitor (3-MA) and by two necroptosis inhibitors (necrostatin and GSK-872), respectively. These results demonstrate lyso-Gb3 induces necroptosis via autophagy and suggest that lyso-Gb3 inflamed retinal pigment epithelial cells trigger endothelial dysfunction via the autophagy-dependent necroptosis pathway. This study suggests the involvement of a novel autophagy-dependent necroptosis pathway in the regulation of endothelial dysfunction in Fabry disease.

• The Korean Journal of Zoology
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• v.29 no.4
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• pp.261-271
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• 1986

The cutaneous xanthophore differentiation from larvae to adult in Bombina orientalis-the Korean fire bellied toad-is studied with light and electron microscopes. General structure of adult xanthophore which is composed of many pterinosomes and a small quantity of carotenoid vesicles is forming chromatophore complex with other dermal pigment cells. And the cytoplasmic process of xanthophore is distributed just beneath the basement membrane. The first differentiated xanthophore is originated from both rER rich cells and Golgi complex rich cells before and after the feeding larval stage. Formation of the pigment granule is proceeded gradually along the sequental metamorphic stages. After the metamorphosis, rapid multiplication of pterinosome is observed and enlargement of carotenoid vesicle is appeared after hybernation. These pigment granules are seen several structures by the differentiated level.

• Journal of Life Science
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• v.30 no.5
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• pp.468-475
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• 2020

The purpose of this study was to investigate antioxidant activity and cell differentiation effects of Monascus purpureus pigment on osteoblast-like MC3T3-E1 cell. In order to examine the antioxidant activities of Monascus purpureus pigment, DPPH radical scavenging, ABTS radical scavenging and SOD-like activities were investigated. DPPH radical and ABTS radical scavenging activities of Monascus purpureus pigment were increased in a dose-dependent manner, and maximum activity were 94% and 99% at a concentration of 1,000 ㎍/ml, respectively. Additionally, SOD-like activity of Monascus purpureus pigment showed 62% at a concentration of 1,000 ㎍/ml. MC3T3-E1 cells did not show cytotoxicity in the concentration range of Monascus purpureus pigment 1~100 ㎍/ml. The ALP activity was increased by addition of Monascus purpureus pigment, and the maximum activity was 124% as compared with control. In addition, nodule formation, a late differentiation factor for bone formation, was increased by adding Monascus purpureus pigment compared to control. These results suggest that Monascus purpureus pigment is expected to be a natural source for developing functional materials to prevent bone-related diseases by osteoblast differentiation.

• Journal of Microbiology and Biotechnology
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• v.14 no.3
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• pp.442-449
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• 2004

Improving the light utilization efficiency of photosynthetic cells in photobioreactors (PBRs) is a major topic in algal biotechnology. Accordingly, in the current study we investigated the effect and suitability of photosynthetic pigment reduction for improving light utilization efficiency. The light-harvesting complex II (LH-II) genes of Rhodobacter sphaeroides were removed to construct a mutant strain with less pigment content. The mutant strain exhibited a slower growth rate than the wild-type under a low light intensity, while the mutant grew faster under a high light intensity. In addition, the specific absorption coefficient was lower in the mutant due to its reduced pigment content, thus it seemed that light penetrated deeper into its culture broth. However, the distance (light penetration depth) from the surface of the PBR to the compensation point did not increase, due to an increase in the compensation irradiance of the mutant strain. Experimental data showed that a reduced photosynthetic pigment content, which lessened the photoinhibition under high-intensity light, helped the volumetric productivity of photosynthetic microorganisms.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.5
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• pp.449-456
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• 2023

N-methyl-D-aspartate (NMDA) receptors are ionic glutamine receptors involved in brain development and functions such as learning and memory formation. NMDA receptor inhibition is associated with autophagy activation. In this study, we investigated whether the NMDA receptor antagonists, memantine and ifenprodil, induce autophagy in human retinal pigment epithelial cells (ARPE-19) to remove N-retinylidene-N-retinylethanolamine (A2E), an intracellular lipofuscin component. Fluorometric analysis using labeled A2E (A2E-BDP) and confocal microscopic examination revealed that low concentrations of NMDA receptor antagonists, which did not induce cytotoxicity, significantly reduced A2E accumulation in ARPE-19 cells. In addition, memantine and ifenprodil activated autophagy in ARPE-19 cells as measured by microtubule-associated protein 1A/1B-light chain3-II formation and phosphorylated p62 protein levels. Further, to understand the correlation between memantine- and ifenprodil-mediated A2E degradation and autophagy, autophagy-related 5 (ATG5) was depleted using RNA interference. Memantine and ifenprodil failed to degrade A2E in ARPE-19 cells lacking ATG5. Taken together, our study indicates that the NMDA receptor antagonists, memantine and ifenprodil, can remove A2E accumulated in cells via autophagy activation in ARPE-19 cells.

• Korean Journal of Ichthyology
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• v.21 no.3
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• pp.208-213
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• 2009

Histological examination of an individual of the Korean slender gudgeon Squalidus gracilis majimae having cutaneous albinism produced rarely in the wild was made and compared with a normal individual. The external body of the albino was colorless, differing from the normal individual, which has dense brownish black spots over its body surface. To make it clear through histological study, we observed eight skin regions: dorsal, lateral, ventral, upper caudal peduncle, lower caudal peduncle, dorsal fin, anal fin, and the eyes. These regional skins were the same in fundamental structure between albinic and normal gudgeon, but there were significant differences in distribution and development of pigment cells (melanins). In the normal gudgeon, the pigment cells were well developed over the regional skins except on the skin from the ventral region. However, it was confirmed in the albino that the pigment cells were vestigial over the upper regions of the eye and body but absent in the ventral region, lower caudal peduncle, and anal fin.

• Biomolecules & Therapeutics
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• v.30 no.3
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• pp.291-297
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• 2022

Dry age-related macular degeneration (AMD) is a type of progressive blindness that is primarily due to dysfunction and the loss of retinal pigment epithelium (RPE). The accumulation of N-retinylidene-N-retinylethanolamine (A2E), a by-product of the visual cycle, causes RPE and photoreceptor degeneration that impairs vision. Genes associated with dry AMD have been identified using a blue light model of A2E accumulation in the retinal pigment epithelium and transcriptomic studies of retinal tissue from patients with AMD. However, dry macular degeneration progresses slowly, and current approaches cannot reveal changes in gene transcription according to stages of AMD progression. Thus, they are limited in terms of identifying genes responsible for pathogenesis. Here, we created a model of long-term exposure to identify temporally-dependent changes in gene expression induced in human retinal pigment epithelial cells (ARPE-19) exposed to blue light and a non-cytotoxic dose of A2E for 120 days. We identified stage-specific genes at 40, 100, and 120 days, respectively. The expression of genes corresponding to epithelial-mesenchymal transition (EMT) during the early stage, glycolysis and angiogenesis during the middle stage, and apoptosis and inflammation pathways during the late stage was significantly altered by A2E and blue light. Changes in the expression of genes at the late stages of the EMT were similar to those found in human eyes with late-stage AMD. Our results provide further insight into the pathogenesis of dry AMD induced by blue light and a novel model in vitro with which relevant genes can be identified in the future.

• Journal of Life Science
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• v.18 no.9
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• pp.1219-1224
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• 2008

The embryonic zebrafish (Danio rerio) is rapidly becoming an important model organism for studies of early events in vertebrate development. Neural crest-derived pigment cell precursors of the embryonic zebrafish give rise to melanophores, xanthophores, and/or iridophores. Cell-signaling mechanisms related to the development of pigmentation and pigment pattern formation remain obscure. In this study, zebrafish embryos were treated with various signaling-related molecules - LiCl (an inositol-phosphatase inhibitor), forskolin (a protein kinase-A activator), a combination of LiCl/forskolin, and LiCl/heparin (an IP3 inhibitor) in order to identify the mechanisms involved in pigmentation. LiCl treatment resulted in ultrastructural and morphological alterations of melanophores. To identify the possible proteins responsible for this ultrastructural and morphological change, phosphorylation patterns in vitro and in vivo were analyzed. LiCl and LiCl/forskolin treatment elicited dramatic increases in the phosphorylation of a 55-kDa protein which was inhibited by heparin treatment. LiCl treatment also induced phosphorylation of a 55-kDa protein in melanophores purified from adult zebrafish. Collectively these results suggest that a LiCl-induced 55-kDa phosphoprotein plays a role in melanophore morphology and ultrastructure and ultimately effects gross pigmentation.

• The Korean Journal of Zoology
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• v.24 no.3
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• pp.133-144
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• 1981

The ultrastructures of the pigment cells in the Asiatic land salamander (Hynobius leechi) dorsal skin were obtained by means of electron microscope. The results were as follows; 1. The pigment cells of the epidermis consisted of the melanocytes in the germinal layer and of the melanophores distributing to the keratinocyte layer. The traits of these cells in the epidermis were as follows: A. The nuclei of the melanocytes were round or oval in shape and appeared as partly small or large infoldings of the nuclear envelope. B. Rough-surfaced endoplasmic reticulums and Golgi complexes were well developed in infranuclear cytoplasm. Many ribosomes were mainly distributed around the perinuclear portion. C. The melanosomes of the melanocytes were observed as a found or an oval shape and strong electron-dense or less electron-dense melanosomes were observed. D. The infoldings of the nuclear envelope in the melanophore were partly found deeper than those of the melanocyte. The cytoplasm of the melanophore filled with melanosomes caused organelles not to be observed in that. 2. The pigment cells in the dermis were composed of the xanthophores just beneath basement membrane and the melanophores in the connective tissue. The traits of these cells in the dermis were as follows: A. The xanthophores contained round or oval vesicles, and these vesicles were divided into 6 types (type I pterinosome, type II pterinosome, type III pterinosomes, type iv pterinosome, type V pterinosome, type VI pterinosome). B. Most of the nuclei of the melanophores in the dermis were elongate in shape, and a portion of the nuclear envelope was deep infolded. C. Becuase the cytoplasm was filled with the melanosomes of the same electron-density, organelles were not observed in the cytoplasm. D. Two processes of the melanophore in the dermis extended in parallel with a xanthophore and the cytoplasm in those processes were filled with the melanosomes.