Search PubMed⌕ Search

Biomedical subjects

Dong Hoon Shin

Publications and source records attributed to Dong Hoon Shin.

At least 19 recordsLinked to original sources

Regulation of UVB-induced IL-8 and MCP-1 production in skin keratinocytes by increasing vitamin C uptake via the redistribution of SVCT-1 from the cytosol to the membrane.

It is well known that UVB (290-320 nm) induces inflammation in skin by the transcription and release of cytokines and chemokines from skin keratinocytes. In addition, it is considered that intracellular reactive oxygen species (ROS) plays an important role in UVB-induced inflammatory response in the skin. Therefore, we investigated the effect of vitamin C, a potent antioxidant, on the regulation of UVB-induced skin inflammation via the modulation of chemokines production. Vitamin C uptake into keratinocytes is increased by UVB irradiation in a time- and dose-dependent manner through the translocation of sodium-dependent vitamin C transporter-1 (SVCT-1), a vitamin C-specific transporter, from the cytosol to the membrane. To evaluate the effect of vitamin C on the chemokine mRNA expression, we performed RNase protection assay. As a result, there was a remarkable change in chemokine mRNA expression, especially IL-8 and monocyte chemoattractant protein (MCP)-1 expression. In addition, increased IL-8 and MCP-1 mRNA expressions were suppressed by vitamin C treatment. We also confirmed the results of protein levels measured by ELISA. Taken together, vitamin C uptake is increased in UVB-irradiated keratinocytes through the translocation of SVCT-1 and regulates inflammatory response in the skin via the downregulation of IL-8 and MCP-1 production.

Antioxidants↗

Immunohistochemical localization of sodium-dependent L-ascorbic acid transporter 1 protein in rat kidney.

Recently, two L-ascorbic acid transporters were identified; sodium-dependent vitamin C transporter (SVCT) 1 and SVCT2. The previous study suggested that SVCT protein might be present on the apical membrane in the straight segment (S3) of proximal tubule. In the present study, SVCT1 immunoreactivity (IR) was observed in the brush border of proximal straight tubules in the medullary ray of renal cortex and the outer stripe of outer medulla, while SVCT2 IR was not localized in any region of the kidney. Since the mechanism of VC reabsorption in the kidney has not been fully elucidated up to the present time, it is meaningful to demonstrate the exact cellular distribution of SVCT protein in the kidney.

Animals↗

Immunohistochemical study on the distribution of TRPC channels in the rat hippocampus.

In the present study, we performed immunohistochemistry using antibodies directed against TRPCs to study the localizations of these channels in rat hippocampus. The pyramidal cell bodies of CA1-3 areas and the granule cell bodies of the dentate gyrus were immunoreactive for TRPC1, TRPC3, TRPC4 and TRPC5. On the other hand, TRPC6 exhibited the cloud-like neuropil staining only in the molecular layer of the dentate gyrus. As a whole, the present study has clearly shown the localization of TRPCs in rat hippocampus and may provide useful data for the future investigations on the structural and functional properties of TRPCs.

Animals↗

Immunohistochemical study of the distribution of sodium-dependent vitamin C transporters in adult rat brain.

Sodium-dependent vitamin C transporters (SVCTs) is known to transport the reduced form of ascorbic acid into the cell, whereas the oxidized form of vitamin C (VC) is moved through a facilitative sugar transporter, such as glucose transporter (GLUT). With regard to the distribution of SVCT1 and -2 within the various organs, they were reported to be expressed in different types of cells. Especially in the central nervous system, only SVCT2 mRNA was expressed mainly in neurons and some types of neuroglial cells. However, data on the expression of SVCT proteins in the brain are scant. Therefore, we tried to develop comprehensive data on the distribution of SVCT proteins in adult rat brain by using immunohistochemical techniques for the first time. In our study, SVCT2 immunoreactivities (IRs) were intensely localized in the neurons of cerebral cortex, hippocampus, and Purkinje cells of cerebellum, and much weaker SVCT2 IRs were found in the other brain regions. Judging from double-immunohistochemical data, most of the cells expressing SVCT2 IRs were likely to be neurons or microglia, even though the cells in choroids plexus or ependymal cells around the ventricles also exhibited SVCT2 IRs. Complete mapping of the distribution of SVCT2 IRs was available by using a semiquantitative method. The subcellular localization of SVCT proteins is necessary for understanding the exact role of the protein, so the current overall mapping of SVCT IRs in the rat brain could be the basis for further studies on related subjects.

Animals↗

Ultramicroscopic study on the hair of newly found 15th century mummy in Daejeon, Korea.

Recent reports on the medieval mummies in Korea have been an invaluable source for the studies on the physical characteristics of medieval Koreans. Though the histological observations on the medieval mummy found in Korea were actively reported by researchers, it could not be said that all the queries on the mummies had been completely answered at the present time. In this study, we tried to add the novel data on the ultramicroscopic characteristics of the hair taken from the recently discovered 15th century mummy, the oldest one ever found in Korea. Even comparing with the hair from living individual, the hair of 15th century mummy showed very intact appearances during observation with electron microscope because the scales on the surface of the mummified hair were not damaged, which were not easily maintained even in living individuals. As to the cause of the excellent preservation of 15th century mummified hair, the presence of surface coat on the hair should be considered. That is, just like the complete sealing effect of lime-soil mixture barrier around the coffin, the presence of the surface coat including calcium and sodium might inhibit the water or fungal infiltrations into the hair shaft.

Hair↗

Protective effect of Rosa laevigata against amyloid beta peptide-induced oxidative stress.

The amyloid beta (Abeta) peptide is known to increase free radical production in nerve cells, leading to cell death. To investigate the effect of Rosa laevigata against Abeta-induced oxidative damage, in vitro assays and in vivo behavioral tests were performed. R. laevigata showed cell protective effects against oxidative stress-induced cytotoxicity. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) reduction assay exhibited significant increase in cell viability when rat pheochromocytoma (PC 12) cells were treated with R. laevigata extracts. Administration of R. laevigata extracts to mice significantly reversed the Abeta-induced learning and memory impairment in in vivo behavioral tests. These results suggest that R. laevigata extracts can reduce the cytotoxicity of Abeta in PC 12 cells, possibly by the reduction of oxidative stress, and these extracts may be useful in the prevention of Alzheimer's disease.

Amyloid beta-Peptides↗

Preserved skin structure of a recently found fifteenth-century mummy in Daejeon, Korea.

Recently published reports on Korea's medieval mummies have been regarded as an invaluable source for studies into the physical characteristics of medieval Koreans. However, even though the mummified tissues have been investigated histologically on various previous occasions, there are many unanswered questions relating to their tissue preservation. The aim of this study was to obtain new data on the ultramicroscopic characteristics of the mummified skin of a fifteenth-century mummy found recently in Daejeon--one of the oldest ever found in Korea. Electron microscopy revealed that much of the epidermis had decayed; what remained of the dermis was filled with collagen fibres and melanin granules or invading bacterial spores present within the mummified epidermis. Considering the histological characteristics shared by naturally formed mummies in different parts of the world, we concluded that the ultramicroscopic patterns of the Daejeon mummy were more comparable with those naturally formed mummies than with artificially formed ones. This is the first full description of the morphological characteristics of the skin collected from this recently found medieval mummy from Daejeon, South Korea.

Burial↗

Endoscopic investigation of the internal organs of a 15th-century child mummy from Yangju, Korea.

Our previous reports on medieval mummies in Korea have provided information on their preservation status. Because invasive techniques cannot easily be applied when investigating such mummies, the need for non-invasive techniques incurring minimal damage has increased among researchers. Therefore, we wished to confirm whether endoscopy, which has been used in non-invasive and minimally invasive studies of mummies around the world, is an effective tool for study of Korean mummies as well. In conducting an endoscopic investigation on a 15th-century child mummy, we found that well-preserved internal organs remained within the thoracic, abdominal and cranial cavities. The internal organs - including the brain, spinal cord, lung, muscles, liver, heart, intestine, diaphragm and mesentery - were easily investigated by endoscopy. Even the stool of the mummy, which accidentally leaked into the abdominal cavity during an endoscopic biopsy, was clearly observed. In addition, unusual nodules were found on the surface of the intestines and liver. Our current study therefore showed that endoscopic observation could provide an invaluable tool for the palaeo-pathological study of Korean mummies. This technique will continue to be used in the study of medieval mummy cases in the future.

Burial↗

Immunohistochemical study on the distribution of sodium-dependent vitamin C transporters in the respiratory system of adult rat.

As vitamin C (L-ascorbic acid, VC) is known to be essential for many enzymatic reactions, the study on the transport mechanism of VC through cytoplasmic membrane is crucial to understanding physiological role of VC in cells and the respiratory system. In this regard, the study on the newly identified sodium-dependent VC transporters (SVCTs), SVCT1 and SVCT2, is required in organs that contain high concentration of VC. We have shown the distribution of SVCT proteins in the respiratory system, which has been reported to be one of the organs with a high concentration of VC, using immunohistochemical techniques. In the present study, intense SVCT immunoreactivities (IRs) were mainly localized in the respiratory system epithelial cells. In the trachea, both SVCT1 and 2 were localized in the psuedostratified ciliated columnar epithelium. In the terminal bronchiole, SVCT1 and 2 IRs were mainly observed in the apical portion of the simple columnar epithelium. In addition, SVCT IRs was localized within the cell membrane of some alveolar cells, even though we could not identify the exact cell types. These results provide the first evidence that intense SVCT1 and 2 IRs were found in the apical portion of the respiratory epithelial cells, suggesting that SVCT proteins in the apical portion could transport the reduced form of VC included in the airway surface liquid into the respiratory epithelial cells.

Animals↗

Polyphenol amentoflavone affords neuroprotection against neonatal hypoxic-ischemic brain damage via multiple mechanisms.

Flavonoids are naturally occurring polyphenolic compounds that have many biological properties, including antioxidative, anti-inflammatory and neuroprotective effects. Here, we report that amentoflavone significantly reduced cell death induced by staurosporine, etoposide and sodium nitroprusside in neuroblastoma SH-SY5Y cells. In post-natal day 7 rats, hypoxic-ischemic (H-I) brain damage induced by unilateral carotid ligation and hypoxia resulted in distinct features of neuronal cell death including apoptosis and necrosis. In this model, a systemic administration of amentoflavone (30 mg/kg) markedly reduced the H-I-induced brain tissue loss with a wide therapeutic time window up to 6 h after the onset of hypoxia. Amentoflavone blocked the activation of caspase 3, characteristic of apoptosis, and the proteolytic cleavage of its substrates following H-I injury. Amentoflavone also reduced the excitotoxic/necrotic cell death after H-I injury in vivo and after oxygen/glucose deprivation in mouse mixed cultures in vitro. Treatment of mouse microglial cells with amentoflavone resulted in a significant decrease in the lipopolysaccharide-induced production of nitric oxide and induction of inducible nitric oxide synthase and cyclo-oxygenase-2. Furthermore, amentoflavone decreased the inflammatory activation of microglia after H-I injury when assessed by the microglial-specific marker OX-42. These data demonstrate for the first time that amentoflavone strongly protects the neonatal brain from H-I injury by blocking multiple cellular events leading to brain damage.

Animals↗

Ultramicroscopic observations on morphological changes in hair during 25 years of weathering.

Weathering or long-term burial may cause profound morphological and histological changes in hair, which may affect the results of forensic and archaeological investigations. We therefore used ultramicroscopic techniques to assay the changes in weathering hair shafts caused by burial for up to 25 years. We found that the middle portion of hair shafts from living individuals shows the expected histological hair structure, while the cuticle layer was absent from the terminal portion of the same hairs, which may be due to the increased weathering experienced by the terminal portion. In hair samples taken 5 years after death, no significant changes in morphology were observed. By 15 years after death, however, we observed losses in various layers of the hair, including the cuticle layer. At 25 years after death, hair shafts showed a number of pores extending into the medulla, with only some hair shafts retaining their cortical layers. To our knowledge, this is the first ultramicroscopic study on weathering of hair for up to 25 years after death. Our results may therefore provide a basis for similar studies in the fields of forensic science and physical anthropology.

Burial↗

Immunohistochemical study of p47Phox and gp91Phox distributions in rat brain.

NADPH oxidase is multi-component enzyme, which comprises the cytosolic proteins p40Phox, p47Phox, and p67Phox and the two membrane proteins, gp91Phox and p22Phox, and which is well characterized in phagocytic cells. NADPH oxidase is a primary source of reactive oxygen species (ROS), and recent studies indicate that free radicals and ROS might be causative factors of several brain degenerative diseases and dysfunctions. However, though previous studies have shown the presence of NADPH oxidase subunits in cell culture and mouse brain, they have not provided detailed high power resolution data. Therefore, we investigated the distributions of the p47Phox and gp91Phox subunits in rat brain using immunohistochemical approach. Cortex, hippocampus, and Purkinje cells of cerebellum were prominently stained by p47Phox and gp91Phox antibodies. As compared with the distributions of p47Phox, gp91Phox in mouse, some differences in the rat brain were observed in the hippocampus, thalamus, amygdala, reticular nucleus, and basal ganglia. Additionally, at the cellular level, most p47Phox immunoreactivity was largely confined to cell bodies and proximal portions of the dendritic tree. Taken together, the widespread observed distributions of p47Phox and gp91Phox subunits indicate that they are probably needed to maintain normal brain function.

Animals↗

Matrix metalloproteinase-3: a novel signaling proteinase from apoptotic neuronal cells that activates microglia.

Microglial activation and inflammation are associated with progressive neuronal apoptosis in neurodegenerative human brain disorders. We sought to investigate molecular signaling mechanisms that govern activation of microglia in apoptotic neuronal degeneration. We report here that the active form of matrix metalloproteinase-3 (MMP-3) was released into the serum-deprived media (SDM) of PC12 cells and other media of apoptotic neuronal cells within 2-6 h of treatment of the cells, and SDM and catalytic domain of recombinant MMP-3 (cMMP-3) activated microglia in primary microglia cultures as well as BV2 cells, a mouse microglia cell line. Both SDM and cMMP-3 induced generation of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), IL-1beta, and interleukin-1 receptor antagonist but not IL-12 and inducible nitric oxide synthase, which are readily induced by lipopolysaccharide, in microglia, suggesting that there is a characteristic pattern of microglial cytokine induction by apoptotic neurons. Neither glial cell line-derived neurotrophic factor nor anti-inflammatory cytokines, such as IL-10 and transforming growth factor-beta1, were induced. SDM and cMMP-3 extensively released TNF-alpha from microglia and activated the nuclear factor-kappaB pathway, and these microglial responses were totally abolished by preincubation with an MMP-3 inhibitor, NNGH [N-isobutyl-N-(4-methoxyphenylsulfonyl)-glycylhydroxamic acid]. MMP-3-mediated microglial activation mostly depended on ERK (extracellular signal-regulated kinase) phosphorylation but not much on either JNK (c-Jun N-terminal protein kinase) or p38 activation. Conditioned medium of SDM- or cMMP-3-activated BV2 cells caused apoptosis of PC12 cells. These results strongly suggest that the distinctive signal of neuronal apoptosis is the release of active form of MMP-3 that activates microglia and subsequently exacerbates neuronal degeneration. Therefore, the release of MMP-3 from apoptotic neurons may play a major role in degenerative human brain disorders, such as Parkinson's disease.

Animals↗

Mechanisms of recurrence in subtypes of ischemic stroke: a hospital-based follow-up study.

BACKGROUND: Information on the mechanism of recurrent stroke may help physicians treating patients with ischemic stroke. However, the mechanisms of recurrence in each stroke subtype are not well known, especially in Asians. OBJECTIVE: To compare the mechanisms of the index and recurrent stroke. DESIGN: Analysis of data from a prospective acute stroke registry. SETTING: University hospital. PATIENTS: Using the clinical syndrome, diffusion-weighted imaging, and vascular studies, we divided 901 patients into 5 groups: large-artery atherosclerosis, cardioembolism, small-artery disease, parent-artery disease occluding the deep perforators, and no determined cause. The patients with large-artery atherosclerosis were subdivided into 2 groups: intracranial and extracranial. MAIN OUTCOME MEASURES: The mechanisms of recurrent vascular events (strokes or coronary heart disease) in subtypes of ischemic stroke were compared. RESULTS: Ninety-three recurrent vascular events (86 strokes and 7 instances of coronary heart disease) were evaluated. The pattern of recurrent stroke differed for the intracranial and extracranial groups; unlike the patients with intracranial large-artery atherosclerosis, recurrent strokes in the extracranial group were often unpredictable with respect to the site of recurrence and degree of preexisting stenosis. None of the patients in the extracranial group had recurrences that were caused by intracranial large-artery atherosclerosis or vice versa. In patients with small-artery disease and stroke with no determined cause, intracranial stenosis was often found at the time of recurrence. CONCLUSIONS: From prognostic and therapeutic perspectives, patients with atherosclerosis should be divided into those with intracranial large-artery atherosclerosis and extracranial large-artery atherosclerosis. In addition, intracranial large-artery atherosclerosis may be important in the development of small-artery disease and stroke with no determined cause, especially in the population with a higher frequency of intracranial large-artery atherosclerosis.

Adult↗

An ultramicroscopic study on the distribution of Müller cell processes in the outer retinal layers of the zebrafish.

The zebrafish, Brachydanio rerio, is a good model for studying the development of various organs. We have assayed the distribution pattern of Müller cell processes in zebrafish retinas by electron microscopy. In the outer nuclear (ON) layer, multiple layers of Müller cell processes were present along both sides of the large pyramidal endings of the synaptic terminals. We found that the inner segments (ISs) of the zebrafish photoreceptors (PRs), including the cones, double cones and rods, were arranged in different planes, and that the Müller cell processes formed multilayered sheaths around virtually all PR compartments except their outer segments. Thus, Müller cell processes beyond the outer limiting membrane (OLM) are more easily observed in zebrafish retina than in the retinas of other species. To our knowledge, this is the first study to show the exact ultrastructural distribution of Müller cell processes around the OLM and the PR layer in zebrafish retina.

Animals↗

Protective effects of aucubin isolated from Eucommia ulmoides against UVB-induced oxidative stress in human skin fibroblasts.

Ultraviolet-B (UVB) irradiation has been demonstrated to produce reactive oxygen species (ROS) in the cells and skin, which induces the synthesis of matrix metalloproteinases (MMPs), causing skin photoaging. Using the human skin fibroblast HS68 cell line in the present study, we investigated the photoprotective effects of aucubin from Eucommia ulmoides. Pretreatment with aucubin significantly inhibited the production of MMP-1 by 57% when compared to the UVB-irradiated cells. Additionally, the senescence-associated beta-galactosidase (SA beta-gal) activity was markedly decreased in the presence of aucubin, which indicates it as an antiphoto-induced aging compound. As the effect of aucubin was determined against ROS, the inhibited ROS formation and malondialdehyde (MDA) levels, and the increased cell viability and glutathione (GSH) level were observed with aucubin under UVB irradiation. Based upon these results, it was suggested that aucubin might play an important role in the cellular defense mechanism against UV radiation-induced photoaging. An understanding of the antioxidant properties of aucubin could, in part, act to elucidate its protective mechanism on the human skin photoaging.

Eucommiaceae↗

A subcellular distribution of estrogen receptor-alpha is changed during artificially induced senescence of PC12 pheochromocytoma cells.

Although estrogen has been considered as a sex hormone for decades, recent reports suggest that estrogen might modulate the development and physiological function of the brain. In addition, the subcellular localization of estrogen receptors (ERs) has shown their presence within both the perinuclear cytoplasm and nuclei, suggesting that these ERs may differ functionally. We, therefore, assayed changes in the subcellular localization of ER-alpha immunoreactivity (IR) in rat pheochromocytoma PC12 cells during the artificial senescence induced by the telomerase inhibitor, 3'-azido-3'-deoxythymidine (AZT). After 2 months of culture with AZT, PC12 cells showed morphological and biochemical characteristics of cellular senescence. In the cells showing artificial senescence, the ER-alpha IR was mainly localized within the cytoplasm, whereas in control cells, ER-alpha IR was found only in the nuclei. Since senescence was induced by AZT, which inhibits the action of telomerase whenever the cells divide, the change in subcellular distribution of ER-alpha IR may be correlated with the length of the telomere.

Animals↗