• Applied Microscopy
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• v.35 no.3
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• pp.165-176
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• 2005

Studies on molecular plasticity of Bermann glia (BG) after harmaline-induced Purkinje cell (PC) degeneration in the rat cerebellum. The intimate structural relationship between BG and PC, evidenced by the sheathing of the PC dendrites by veil-like process from the BG has been suggestive of the close functional relationship between these two cell types. However, little is known about metabolic couplings between these cells. This study designed to investigate molecular plasticity of BG in the rat cerebellum in which PCs were chemically ablated by harmaline treatment. Immunohistochemical examination reveals that harmaline induced PC degeneration causes a marked glial reaction in the cerebellum with activated BG and microglia aligned in parasagittal stripes within the vermis. In these strips, activated BG were associated with upregulaion of metallotheionein, while GLAST and was down regulated, as compared with nearby intact area where both BG are in contact with PCs. The data from this study demonstrate that BG can change their phenotypic expression when BG loose their contact with PCs. It is conceivable that activated BG may upregulate structural proteins, metallothionein expression to use for their proliferation and hypertrophy; metallothionein expression to cope with oxidative stress induced by PC degeneration and microglial activation. On the contrary, BG may down regulated expression of GLAST because sustained loss of contact with PCs would eliminate the necessity for the cellular machinery involved glutamate metabolism. In conclusion, BG might respond man to death of PCs by undergoing a change in metabolic state. It seems possible that signaling molecules released from PCs regulates the phenotype expression of BG. Also ultrastructures in the organelles of normal PC and BG are distinguished by mitochondrial appearance, and distributed vesicles at the synaptic area in the cytoplasm.

• Biomolecules & Therapeutics
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• v.11 no.2
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• pp.112-118
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• 2003

1-Methylated $\beta$-carbolines (harmaline and harmalol) and antioxidants (N-acetylcysteine and ascorbate) reduced the loss of cell viability in differentiated PC 12 cells treated with 5 mM glutamate. $\beta$-Carbolines prevented the glutamate-induced decrease in mitochondrial membrane potential, cytochrome c release and caspase-3 activation in PC 12 cells. $\beta$-Carbolines reduced the formation of reactive oxygen species and depletion of glutathione due to glutamate in PC12 cells. $\beta$-Carbolines revealed a scavenging action on hydrogen peroxide and reduced the iron and EDTA-mediated degradation of 2-deoxy-D-ribose. The results suggest that I-methylated $\beta$-carbolines attenuate the cytotoxic effect of glutamate on PC12 cells by reducing the alteration of mitochondrial membrane permeability that seems to be mediated by oxidative stress.

• The Korean Journal of Physiology
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• v.22 no.2
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• pp.307-318
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• 1988

Properties of succinate transport were examined in basolaterat membrane vesicles (BLMV) isolated from rabbit renal cortex. An inwardly directed $Na^+$ gradient stimulated succinate uptake and led to a transient overshoot. $K^+,{\;}Li^+,{\;}Rb^+$ and choline could not substitute for $Na^+$ in the uptake process. The dependence of the initial uptake rate of succinate on $Na^+$ concentration exhibited sigmoidal kinetics, indicating interaction of more than one $Na^+$ with transporter Hill coefficient for $Na^+$ was calculated to be 2.0. The $Na^+-dependent$ succinate uptake was electrogenic, resulting in the transfer of positive charge across the membrane. The succinate uptake into BLMV showed a pH optimum at external pH $7.5{\sim}8.0$, whereas succinate uptake into brush border membrane vesicles (BBMV) did not depend on external pH. Kinetic analysis showed that a Na-dependent succinate uptake in BLMV occurred via a single transport system, with an apparent Km of $15.5{\pm}0.94{\;}{\mu}M$ and Vmax of $16.22{\pm}0.25{\;}nmole/mg{\;}protein/min$. Succinate uptake was strongly inhibited by $4{\sim}5$ carbon dicarboxylates, whereas monocarboxylates and other organic anions showed a little or no effect. The succinate transport system preferred dicarboxylates in trans-configuration (furmarate) over cis-dicarboxylates (maleate). Succinate uptake was inhibited by the anion transport inhibitors DIDS, SITS and furosemide, and $Na^+-coupled$ transport inhibitor harmaline. These results indicate the existence of a $Na^+-dependent$ succinate transport system in BLMV that may be shared by the other Krebs cycle intemediates. This transport system seems to be very similar to the luminal transport system for dicarboxylates.

• The Korean Journal of Physiology
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• v.21 no.2
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• pp.283-289
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• 1987

Uric acid transport across the basolateral membrane of renal proximal tubules was studied in rabbit kidney cortical slices. Uric acid uptake was greater under $O_2$ atmosphere compared to under $N_2$ atmosphere, and was increased with $Na^{2+}$ concentration in incubation medium. Uric acid inhibited PAH uptake but not TEA uptake and did trans-stimulated PAH efflux. PAH also inhibited uric acid uptake. Uric acid uptake was inhibited by harmaline, ouabin, SITS, DIDS and pyrazinoic acid. The inhibition of PAH uptake by these inhibitors also was reasonably comparable to that of uric acid uptake. These results suggest that uric acid was transported across the basolateral membrane of renal tubule by a carrier-mediated process which was by a common transport system with PAH in rabbit.

• Biomolecules & Therapeutics
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• v.12 no.1
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• pp.9-18
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• 2004

Opening of the mitochondrial permeability transition pore has been recognized to be involved in cell death. The present study investigated the effect of ${\beta}$-carbolines (harmaline and harmalol) and deprenyl on the dopamine-induced change in the mitochondrial membrane permeability and cell death in differentiated PC12 cells. Cell death due to 250 4{\mu}$M dopamine was inhibited by caspase inhibitors (z-IETD.fmk, z-LEHD.fmk and z-DQMD.fmk) and antioxidants (N-acetylcysteine, ascorbate, superoxide dismutase, catalase and carboxy-PTIO). ${\beta}$-Carbolines prevented the dopamine-induced cell death in PCl2 cells, while deprenyl did not inhibit cell death. ${\beta}$-Carbolines decreased the condensation and fragmentation of nuclei caused by dopamine in PC12 cells. ${\beta}$-Carbolines inhibited the decrease in mitochondrial transmembrane potential, cytochrome c release, formation of reactive oxygen species and depletion of GSH caused by dopamine in PC12 cells, whereas deprenyl did not decrease dopamine-induced mitochondrial damage. ${\beta}$-Carbolines, deprenyl and antioxidants depressed the formation of nitric oxide and melanin in dopamine-treated PC12 cells. The results suggest that cell death due to dopamine PC12 cells is mediated by caspase-8, -9 and -3. Unlike deprenyl, ${\beta}$-carbolines may attenuate the dopamineinduced cell death in PC12 cells by suppressing change in the mitochondrial membrane permeability through inhibition of the toxic action of reactive oxygen and nitrogen species.

• Advances in Traditional Medicine
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• v.7 no.4
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• pp.395-408
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• 2007

This study reports the analgesic, anti-inflammatory and membrane-stabilizing property of alcoholic extract of Ophiorrhiza nicobarica (ON), a wild herb, used as an anti-infective ethnomedicine of Nicobarese and Shompen tribes of Great Nicobar Island, India. We for the first time investigated the analgesic and antiinflammatory potential of this herb in acute, subacute and chronic model of inflammation in Swiss albino mice and Wistar albino rats, along with sheep RBC-induced sensitivity and membrane stabilization. The acetic acid induced writhing, tail flick and tail immersion tests are used as a model for evaluating analgesic activity; while the carrageenin-induced paw oedema was used as the model for acute inflammation, dextran-induced oedema as sub-acute and cotton-pellateinduced granuloma as chronic inflammatory model. The probable mode by which ON mediate its effect on inflammatory conditions was studied on sheep RBC-induced sensitivity and membrane stabilization. The in vitro results revealed that the ON extract possesses significant (P < 0.05) dose dependent analgesic and antiinflammatory activity at 200 and 300 mg/kg and its fractions at 50 mg/kg, p.o. respectively, compared to the control groups. However, the extract failed to exhibit membrane-stabilizing property as it unable to reduce the level of haemolysis of RBC exposed to hypotonic solution. The acute toxicity studies of ON extract in rats and mice revealed that the extract was nontoxic even up to 3.0 g/kg body weight of the animals, with a high safety profile. We have isolated ursolic acid, ${\beta}$-sitosterol and harmaline respectively, from the bioactive part of the extract. The results indicated that the O. nicobarica is indeed beneficial in primary health care, and suggest that its anti-inflammatory activity may not be related to membrane-stabilization.

• Journal of the Korean Society of Physical Medicine
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• v.5 no.3
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• pp.455-465
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• 2010

Purpose : This study is intended to examine the motor skill learning on balance and coordination in the cerebellar injured rats by 3AP. Methods : This study selected 60 Sprague-Dawley rats of 8 weeks. Experiment groups were divided into four groups and assigned 15 rats to each group. Group I was a normal control group(induced by saline); Group II was a experimental control group(cerebellar injured by 3AP); Group III was a group of motor skill learning after cerebellar injured by 3AP; Group IV was a group of treadmill exercise after cerebellar injured by 3AP. In each group, motor performance test, histologic observations, synaptophysin expression and electron microscopy observation were analyzed. Results : In motor performance test, the outcome of group II was significantly lower than the group III, IV(especially group III)(p<.001). In histological finding, the experimental groups were destroy of dendrities and nucleus of cerebellar neurons. Group III, IV were decreased in degeneration of cerebellar neurons(especially group III). In immunohistochemistric response of synaptophysin in cerebellar cortex, experimental groups were decreased than group I. Group III's expression of synaptophysin was more increased than group II, IV. In electron microscopy finding, the experimental groups were degenerated of Purkinje cell. Conclusion : These result suggest that improved motor performance by motor skill learning after harmaline induced is associated with dynamically altered expression of synaptophysin in cerebellar cortex and that is related with synaptic plasticity.