Biomedical subjects

Sun Young Shin

Publications and source records attributed to Sun Young Shin.

9 recordsLinked to original sources

PubMed2006

Presenilin mutations linked to familial Alzheimer's disease cause an imbalance in phosphatidylinositol 4,5-bisphosphate metabolism.

Phosphatidylinositol 4,5-bisphosphate (PIP2) is an important cellular effector whose functions include the regulation of ion channels and membrane trafficking. Aberrant PIP2 metabolism has also been implicated in a variety of human disease states, e.g., cancer and diabetes. Here we report that familial Alzheimer's disease (FAD)-associated presenilin mutations cause an imbalance in PIP2 metabolism. We find that the transient receptor potential melastatin 7 (TRPM7)-associated Mg2+ -inhibited cation (MIC) channel underlies ion channel dysfunction in presenilin FAD mutant cells, and the observed channel deficits are restored by the addition of PIP2, a known regulator of the MIC/TRPM7 channel. Lipid analyses show that PIP2 turnover is selectively affected in FAD mutant presenilin cells. We also find that modulation of cellular PIP2 closely correlates with 42-residue amyloid beta-peptide (Abeta42) levels. Our data suggest that PIP2 imbalance may contribute to Alzheimer's disease pathogenesis by affecting multiple cellular pathways, such as the generation of toxic Abeta42 as well as the activity of the MIC/TRPM7 channel, which has been linked to other neurodegenerative conditions. Thus, our study suggests that brain-specific modulation of PIP2 may offer a therapeutic approach in Alzheimer's disease.

Alzheimer Disease↗

PubMed2006

Conjunctival changes induced by LASIK suction ring in a rabbit model.

PURPOSE: To study histopathological changes in rabbit conjunctiva after suction ring application. METHODS: A suction ring was applied to adult albino rabbit eyes (n = 30) with a vacuum pressure of 508 mm Hg for 40 s. Three rabbits were sacrificed at 3 h (3-hour group), 6 h (6-hour group), 1 day (1-day group), 3 days (3-day group), and 7 days (7-day group) after the suction ring application. Histopathological examinations included hematoxylin and eosin, Alcian blue pH 2.5-periodic acid-Schiff (AB2.5-PAS), and Alcian blue pH 1.0-periodic acid-Schiff (AB1.0-PAS) staining. TdT-dUTP-terminal nick-end labeling (TUNEL) assay and immunohistochemical staining for p65 were also performed. RESULTS: The site of suction ring application and adjacent areas did not show transient inflammation. AB2.5-PAS staining revealed that the percentage of neutral mucin was significantly different between 54.5 +/- 1.6% in the control group and 22.3 +/- 1.3% in the 7-day group (p = 0.04). Apoptosis occurred not only at the site of suction ring application, but also in adjacent regions. At all time points, conjunctival epithelium showed no positive staining for p65. CONCLUSION: The transient elevation of pressure induced by a suction ring is sufficient to cause conjunctival damage. These histological results support the finding that conjunctival damage caused by suction ring application is one of many etiologies of dry eye syndrome following laser in situ keratomileusis.

Alcian Blue↗

PubMed2006

A case of multiple cranial nerve palsies as the initial ophthalmic presentation of antiphospholipid syndrome.

PURPOSE: To report a case of third, fourth, and six cranial nerve palsies with antiphospholipid syndrome (APS). METHODS: Medical records of a 16-year-old female diagnosed with idiopathic intracranial hypertension (IIH) in primary APS were reviewed. RESULTS: A 16-year-old female presented with headache and diplopia. Ocular examinations revealed marked bilateral disc edema. She was unable to depress, adduct, and abduct in left eye and had limited abduction in the right eye. Cerebrospinal fluid had a normal composition and a pressure of 400 mmH20. Lupus anticoagulant and IgG anticardiolipin antibody were positive. There was no clinical evidence of other autoimmune disease. Brain magnetic resonance (MR) imaging, MR angiography, and conventional angiogram with venous phase were normal. She was diagnosed with bilateral sixth, and left third and fourth cranial nerve palsies secondary to idiopathic intracranial hypertension in primary APS. CONCLUSIONS: To our knowledge this is the first reported case of concurrent third, fourth, and sixth cranial nerve palsies in a patient with primary APS.

Abducens Nerve Diseases↗

PubMed2005

Regulation of magnesium-inhibited cation current by actin cytoskeleton rearrangement.

Magnesium-inhibited, non-selective cation current (I(MIC)) is activated by depletion of intracellular Mg(2+) and ATP. I(MIC) transports various divalent cations including Mg(2+) and Ca(2+), and is involved in cell viability. We investigated the effect of actin dynamics on I(MIC). Formation of a stable cortical actin network by calyculin A inhibited the activation of I(MIC), while the actin depolymerizing reagent, cytochalasin D, reversed the inhibition. Induction of a dense cortical actin layer by transfecting the constitutively active form of RhoA also inhibited the activation of I(MIC). These results suggest that the activation of I(MIC) may be dynamically regulated by actin cytoskeleton rearrangement.

Actin Cytoskeleton↗

PubMed2004

Evidence for Na+/Ca2+ exchanger 1 association with caveolin-1 and -2 in C6 glioma cells.

The purpose of this study is to understand the interaction of Na + -Ca2+ exchanger (NCX1), that is one of the essential regulators of Ca2+ homeostasis, with caveolin (Cav)-1 and Cav-2 in Cav-3 null cell (rat C6 glioma cell). Both mRNA and protein expression of NCX1, Cav-1 and Cav-2 was observed, but no expression of mRNA and protein of Cav-3 were observed in C6 glioma cells. In isolated caveolae-enriched membrane fraction, the NCX1, Cav-1 and Cav-2 proteins localized in same fractions. The experiment of immuno-precipitation showed complex formation between the NCX1 and Cavs. Confocal microscopy also supported co-localization of NCX1and Cavs at the plasma membrane. Functionally, sodium-free induced forward mode of NCX1 attenuated by Cav-1 antisense ODN. When treated cells with Cav-2 antisense ODN, both reverse and forward mode of NCX1 was attenuated. From these results, in the Cav-3 lacking cells, the function of NCX1 might be regulated by binding with Cavs. Considering the decrement of NCX1 activity by antisense ODNs, caveolins may play an important role in diverse of pathophysiological process of NCX1-related disorders in the body.

Animals↗

PubMed2003

Adrenergic regulation of the intracellular [Ca2+] and voltage-operated Ca2+ channel currents in the rat prostate neuroendocrine cells.

BACKGROUND: The prostate gland contains numerous neuroendocrine cells (PNECs) innervated by adrenergic neurons. PNECs are believed to influence the growth and physiological function of the prostate gland via paracrine release of hormones. MATERIALS AND METHODS: Using fura-2 fluorescence measurement and patch-clamp techniques, we investigated the effects of adrenergic stimulation on cytosolic concentration of Ca2+ ([Ca2+]c) and high voltage-activated Ca2+ channel currents (HVA-I(Ca)) of the putative rat prostate neuroendocrine cells (RPNECs) freshly isolated by an enzymic digestion. RESULTS: Noradrenaline (NA, 1 microM) induced a sharp, transient increase of [Ca2+]c measured by the fura-2 fluorescence. Pharmacological studies showed that alpha1-adrenoceptors (alpha1-ARs) coupled with PLC/IP3 signaling pathway induce the release of stored Ca2+, which subsequently recruits store-operated Ca2+ entry pathways. In the whole-cell voltage clamp experiment, NA decreased the amplitude of HVA-I(Ca) by 40%, which was mimicked by an alpha2-AR agonist (UK14304) but not by an alpha1-AR agonist (phenyleprine). After selective blockade of N-type Ca2+ channels by omega-conotoxin GVIA, the addition of NA showed no further inhibition on the remaining L-type Ca2+ channel currents. The adrenergic inhibition of HVA-I(Ca) was partially prevented by the pretreatment with pertussis toxin (PTX) (5 microg/ml, 4 hr, 37 degrees C). CONCLUSIONS: RPNECs express both alpha1- and alpha2-ARs, signaling the release of stored Ca2+ and the inhibition of N-type Ca2+ channels, respectively.

Adrenergic alpha-Agonists↗

PubMed2003

Ca2+-activated Cl- channel currents in rat ventral prostate epithelial cells.

BACKGROUND: In many epithelial tissues, the Cl(-) efflux via Ca(2+)-activated Cl(-) channels (Cl(Ca)) play a key role for the fluid secretion. To elucidate the mechanism of prostatic fluid secretion, the properties of whole-cell chloride conductance were investigated. MATERIALS AND METHODS: Rat prostate secretory epithelial cells (RPSECs) were isolated by collagenase treatment, and were used for the whole-cell voltage clamp. Both extra- and intracellular monovalent cations were replaced by N-methyl-D-glucamate to record the Cl(-) current selectively. RESULTS: A bath application of Ca(2+)-ionophore, ionomycin (0.2 micro M), increased the membrane conductance with outwardly rectifying voltage-dependence. On step-like depolarization from -60 to +80 mV (500 msec), the ionomycin-induced current showed slowly activating kinetics, a known property of Cl(Ca) current (I(Cl(Ca))) of other tissues. The relative permeability of Cl(Ca) to various anions was calculated from the reversal potentials measured under a total replacement of extracellular Cl(-) with various anions, and the relative order of permeability was SCN(-)>I(-)>Br(-)>Cl(-)>>gluconate. The amplitude of I(Cl(Ca)) was decreased by various anion channel blockers: niflumic acid (100 micro M), DPC (100 micro M), DIDS (1 mM), and NPPB (200 micro M). CONCLUSIONS: RPSECs have Cl(Ca) that may provide Cl(-) efflux pathways for the exocrine secretions of the prostate.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed2003

Voltage-dependent ion channel currents in putative neuroendocrine cells dissociated from the ventral prostate of rat.

Prostate neuroendocrine (NE) cells play important roles in the growth and differentiation of the prostate. Following enzymatic digestion of rat ventral prostate, the whole-cell patch-clamp technique was applied to dark, round cells that exhibited chromogranin-A immunoreactivity, a representative marker of NE cells. Under zero current-clamp conditions, putative NE cells showed hyperpolarized resting membrane potentials of some -70 mV, and spontaneous action potentials were induced by an increase in external [K+] or by the injection of current. Using a CsCl pipette solution, step-like depolarization activated high-voltage-activated Ca2+ current (HVA I(Ca)) and tetrodotoxin-resistant voltage-activated Na+ current. The HVA I(Ca) was blocked by nifedipine and omega-conotoxin GVIA, L-type and N-type Ca2+ channel blockers, respectively. Using a KCl pipette solution, the transient outward K+ current (I(to)), Ca2+ -activated K+ currents (I(K,Ca)), the non-inactivating outward current and an inwardly rectifying K+ current (I(Kir)) were identified. I(K,Ca) was suppressed by charybdotoxin (50 nM), iberiotoxin (10 nM) or clotrimazol (1 microM), but not by apamine (100 nM). I(to) was inhibited by 4-aminopyridine (5 mM). I(Kir) was identified as a Ba2+ -sensitive inwardly rectifying current in the presence of a high-K+ bath solution. The voltage- and Ca2+ -activated ion channels could play significant roles in the regulation of neurohormonal secretion in the prostate.

Animals↗

PubMedDate not supplied

Expression of four growth factors in recessed extraocular muscles of rabbits.

BACKGROUND AND OBJECTIVE: The study was designed to determine the temporal expression of insulin-like growth factor (IGF)-I, IGF-II, basic fibroblast factor 2 (bFGF-2), and transforming growth factor beta 1 (TGF-beta1) in recessed extraocular muscles. MATERIALS AND METHODS: Sixteen eyes of eight rabbits were subjected to conventional 4-mm recession of superior rectus muscles. Two rabbits were untreated as control. The rabbits were killed and their eyes were enucleated at 3 (group 3), 6 (group 6), 24 (group 24), and 72 (group 72) hours after the operation (two rabbits per group), and the expression of IGF-I, IGF-II, bFGF-2, and TGF-beta1 was immunohistochemically examined. RESULTS: The peak levels of IGF-I, IGF-II, and TGF-beta1 expression were observed in groups 24, 6, and 3, respectively. However, bFGF-2 was less expressed than the other growth factors in all groups. CONCLUSIONS: IGF-I, IGF-II, bFGF-2, and TGF-beta1 in regenerating muscle cells were expressed by different kinetics, suggesting a distinct role of each growth factor during wound healing after recession of extraocular muscles.

Animals↗