• Archives of Pharmacal Research
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• 제27권12호
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• pp.1275-1283
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• 2004

Fate of the nascent thyrolglobulin (Tg) molecule is characterized by multimerization. To establish the formation of Tg multimers, the partially unfolded/reduced Tg or deoxycholate-treated/ reduced Tg was subjected to protein disulfide isomerase (PDI)-mediated multimerization. Oxidized glutathione/PDI-mediated formation of multimeric Tg forms, requiring at least an equivalent molar ratio of PDI/Tg monomer, decreased with increasing concentration of reduced glutathione (GSH), suggesting the oxidizing role of PDI. Additional support was obtained when PDI alone, at a PDI/Tg molar ratio of 0.3, expressed a rapid multimerization. Independently, the exposure of partially unfolded Tg to GSH resulted in Tg multimerization, enhanced by PDI, according to thiol-disulfide exchange. Though to a lower extent, a similar result was observed with the dimerization of deoxycholate-pretreated Tg monomer. Consequently, it is implied that intermolecular disulfide linkage may be facilitated at a limited region of unfolded Tg. In an attempt to examine the multimerization site, the cysteine residue-rich fragments of the Tg were subjected to GSH-induced multimerization; a 50 kDa fragment, containing three vicinal dithiols, was multimerized, while an N-terminal domain was not. Present results suggest that the oxidase as well as isomerase function of PDI may be involved in the multimerization of partially unfolded Tg or deoxycholate-treated Tg.

• 대한수의학회지
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• 제57권1호
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• pp.1-7
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• 2017

Parkinson's disease (PD) is an irreversible neurological disorder with related locomotor dysfunction and is characterized by the selective loss of nigral neurons. PD can be experimentally induced by 6-hydroxydopamine (6-OHDA). It has been reported that reactive oxygen species, which deplete endogenous glutathione (GSH) levels, may play important roles in the dopaminergic cell death characteristic of PD. Fucoidan, a sulfated algal polysaccharide, exhibits anti-inflammatory and anti-oxidant actions. In this study, we investigated whether fucoidan can protect against 6-OHDA-mediated cytotoxicity in SH-SY5Y cells. Cytotoxicity was evaluated by using MTT and LDH assays. Fucoidan alleviated cell damage evoked by 6-OHDA dose-dependently. Fucoidan reduced the number of apoptotic nuclei and the extent of annexin-V-associated apoptosis, as revealed by DAPI staining and flow cytometry. Elevation of lipid peroxidation and caspase-3/7 activities induced by 6-OHDA was attenuated by fucoidan, which also protected against cytotoxicity evoked by buthionine-sulfoximine-mediated GSH depletion. Reduction in the glutathione/glutathione disulfide ratio induced by 6-OHDA was reversed by fucoidan, which also inhibited 6-OHDA-induced disruption of mitochondrial membrane potential. The results indicate that fucoidan may have protective action against 6-OHDA-mediated neurotoxicity by modulating oxidative injury and apoptosis through GSH depletion.

• Plant Biotechnology Reports
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• 제5권4호
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• pp.353-365
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• 2011

The present study investigates the possible regulatory role of exogenous nitric oxide (NO) in antioxidant defense and methylglyoxal (MG) detoxification systems of wheat seedlings exposed to salt stress (150 and 300 mM NaCl, 4 days). Seedlings were pre-treated for 24 h with 1 mM sodium nitroprusside, a NO donor, and then subjected to salt stress. The ascorbate (AsA) content decreased significantly with increased salt stress. The amount of reduced glutathione (GSH) and glutathione disulfide (GSSG) and the GSH/GSSG ratio increased with an increase in the level of salt stress. The glutathione S-transferase (GST) activity increased significantly with severe salt stress (300 mM). The ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), catalase (CAT) and glutathione peroxidase (GPX) activities did not show significant changes in response to salt stress. The glutathione reductase (GR), glyoxalase I (Gly I), and glyoxalase II (Gly II) activities decreased upon the imposition of salt stress, especially at 300 mM NaCl, with a concomitant increase in the $H_2O_2$ and lipid peroxidation levels. Exogenous NO pretreatment of the seedlings had little influence on the nonenzymatic and enzymatic components compared to the seedlings of the untreated control. Further investigation revealed that NO pre-treatment had a synergistic effect; that is, the pre-treatment increased the AsA and GSH content and the GSH/GSSG ratio, as well as the activities of MDHAR, DHAR, GR, GST, GPX, Gly I, and Gly II in most of the seedlings subjected to salt stress. These results suggest that the exogenous application of NO rendered the plants more tolerant to salinity-induced oxidative damage by enhancing their antioxidant defense and MG detoxification systems.

• Biomolecules & Therapeutics
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• 제13권3호
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• pp.127-132
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• 2005

We investigated whether ischemic preconditioning (IPC) protects liver against cold ischemic injury using isolated perfused rat liver. Rat livers were preconditioned by 5 minutes of ischemia and 5 minutes of reperfusion and preserved for 30 hours at $4^{\circ}C$ in University of Wisconsin solution. Livers were then reperfused for 120 minutes. Oxygen uptake and bile flow in ischemic livers markedly decreased during reperfusion. These decreases were prevented by IPC. Portal pressure was elevated in cold ischemic and reperfused livers and this elevation was prevented by IPC. Lactate dehydrogenase and purine nucleoside phosphorylase activities markedly increased during reperfusion. These increases were prevented by IPC. The ratio of reduced glutathione to glutathione disulfide was lower in ischemic livers. This decrease was prevented by IPe. Our findings suggest that IPC protects the liver against the deleterious effect of cold ischemia/reperfusion, and this protection is associated with the reduced oxidative stress.

• Biomolecules & Therapeutics
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• 제21권2호
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• pp.132-137
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• 2013

Geniposide is an active product extracted from the gardenia fruit, and is one of the most widely used herbal preparations for liver disorders. This study examined the cytoprotective properties of geniposide and its metabolite, genipin, against hepatic ischemia/reperfusion (I/R) injury. C57BL/6 mice were subjected to 60 min of ischemia followed by 6 h of reperfusion. Geniposide (100 mg/kg) and genipin (50 mg/kg) were administered orally 30 min before ischemia. In the I/R mice, the levels of serum alanine aminotransferase and hepatic lipid peroxidation were elevated, whereas hepatic glutathione/glutathione disulfide ratio was decreased. These changes were attenuated by geniposide and genipin administration. On the other hand, increased hepatic heme oxygenase-1 protein expression was potentiated by geniposide and genipin administration. The increased levels of tBid, cytochrome c protein expression and caspase-3 activity were attenuated by geniposide and genipin. Increased apoptotic cells in the I/R mice were also significantly reduced by geniposide and genipin treatment. Our results suggest that geniposide and genipin offer significant hepatoprotection against I/R injury by reducing oxidative stress and apoptosis.

• Environmental Analysis Health and Toxicology
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• 제24권4호
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• pp.303-309
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• 2009

Hepatic antioxidant defense systems were examined in rats treated with tetrabromobisphenol-A (TBBPA), a brominated flame retardant, at the doses of 0, 250, 500 and 1,000 mg/kg for four weeks. Hepatic ratio of glutathione disulfide to glutathione (GSH) and levels of malondialdehyde, oxidative stress markers were not changed in rats treated with TBBPA. Hepatic expression of antioxidant enzymes including GSH peroxdiase-1 (GPX-1)/GSH reductase (GR), alpha-, mu- and pi-class glutathione-S-transferase (GST) and gamma-glutamylcysteine ligase catalytic subunit was determined using immunoblot analysis. Alpha-class GSTs, GPX-1 and GR levels were significantly decreased in rats treated with TBBPA at the dose of 500 or 1,000 mg/kg. These results show that TBBPA results in down-regulation of hepatic expression of antioxidant enzymes related with GSH, suggesting the liver in TBBPA-treated rats may be more sensitive to oxidants.