• Proceedings of the Korean Society of Toxicology Conference
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• 2002.05a
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• pp.89-89
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• 2002

It is well known that oxygen radicals induce neuronal cell damage by initiation of lipid peroxidation chain reaction. Recent work has been also demonstrated that enzymatically generated free radicals cause the release of glutamate and aspartate from cultured rat hippocampal slices.(omitted)

• The Korean Journal of Nuclear Medicine
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• v.32 no.4
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• pp.391-395
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• 1998

Purpose: Chitin and chitosan are nontoxic natural chelators that chelate radiostrontium effectively. The purpose of this study was to compare radiostrontium chelation of chitin and chitosan with that of well known chemical chelators, namely EDTA and DTPA. Materials and Methods: The chelaton rates of chitin, chitosan, EDTA and DTPA were compared using a column chromatography method (Sephadex G-25M, Sweden). Three kinds of chitins and four kinds of chitosans were used. All of them were water soluble. Results: Phosphated chitosan showed the highest chelation yield of 97% at pH 7. All of chitins, chitosans, EDTA and DTPA showed chelation yield of more than 90% independent of varing pH level. Conclusion: Chitin and chitosan have similar chelation rate as compared with EDTA and DTPA.

• Journal of Microbiology
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• v.41 no.4
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• pp.289-294
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• 2003

Gelatinase is a proteolytic enzyme that hydrolyzes gelatin. Gelatinolytic activity was detected from culture broths of Streptomyces griseus IFO13350 and HH1 by paper disc assays on 0.5% agar plates containing 1% gelatin. The concentrated extracellular protein from the S. griseus was analyzed by SDS polyacrylamide gel, and two proteins, with molecular weights of 30 and 28 kDa, respectively, were identified to have gelatinase activity by gelatin zymography. The protein with a molecular weight of 28 kDa was confirmed to be S. griseus trypsin (SGT). The effects of metal ions and metal chelators on the protease activity of the SGT were studied. Of the metal ions tested, only manganese was found to enhance the protease activity, 2.6 times, however, $Co^{2+},\;Cu^{2+},\;and\;Zn^{2+}$, and metal chelators, such as EDTA and EGTA, inhibited the SGT activity. When the protease activity of the SGT was measured at various pHs, in the presence of 5 mM $MnCl_2$, its highest activity was at pH 11.0, whereas only 60% of the maximum activity was observed between pHs 4.0 and pH 6.0, and almost 80% activity between pHs 7.0 to pH 10.0. The protease activity was measured at various temperatures in the presence of 5 mM $MnCl_2$. The SGT was found to be stable up to $60^{\circ}C$ for 30 min, while only 16% of the enzyme activity remained at $60^{\circ}C$, and at $80^{\circ}C$ almost all the activity was lost. The optimal temperature for the protease activity was $50^{\circ}C$.

• Toxicological Research
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• v.35 no.1
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• pp.83-91
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• 2019

Nanoparticles (NPs) have been recognized as both useful tools and potentially toxic materials in various industrial and medicinal fields. Previously, we found that zinc oxide (ZnO) NPs that are neurotoxic to human dopaminergic neuroblastoma SH-SY5Y cells are mediated by lipoxygenase (LOX), not cyclooxygenase-2 (COX-2). Here, we examined whether human bone marrow-derived mesenchymal stem cells (MSCs), which are different from neuroblastoma cells, might exhibit COX-2- and/or LOX-dependent cytotoxicity of ZnO NPs. Additionally, changes in annexin V expression, caspase-3/7 activity, and mitochondrial membrane potential (MMP) induced by ZnO NPs and ZnO were compared at 12 hr and 24 hr after exposure using flow cytometry. Cytotoxicity was measured based on lactate dehydrogenase activity and confirmed by trypan blue staining. Rescue studies were executed using zinc or iron chelators. ZnO NPs and ZnO showed similar dose-dependent and significant cytotoxic effects at concentrations ${\geq}15{\mu}g/mL$, in accordance with annexin V expression, caspase-3/7 activity, and MMP results. Human MSCs exhibited both COX-2 and LOX-mediated cytotoxicity after exposure to ZnO NPs, which was different from human neuroblastoma cells. Zinc and iron chelators significantly attenuated ZnO NPs-induced toxicity. Conclusively, these results suggest that ZnO NPs exhibit both COX-2- and LOX-mediated apoptosis by the participation of mitochondrial dysfunction in human MSC cultures.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.5 no.2
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• pp.135-144
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• 2019

Targeted alpha therapy (TAT) based on metallic radionuclides has attracted a lot of attention lately due to its impressive therapeutic efficacy displayed in couple of clinical studies for cancer. Representative metallic radionuclides emitting alpha-particle include 225Ac, 213Bi, and 227Th, and there have been variety of TAT formulations based on different targeting moiety and chelating agents. In this review, we introduce strategies to label metallic radioisotopes with biomolecules and look at some of recent preclinical and clinical results of TAT for cancer.

• BMB Reports
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• v.39 no.3
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• pp.335-338
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• 2006

Methylglyoxal (MG) is an endogenous physiological metabolite which is present in increased concentrations in diabetics. MG reacts with the amino acids of proteins to form advanced glycation end products. In this in vitro study, we investigated the effect of MG on the structure and function of ceruloplasmin (CP) a serum oxidase carrier of copper ions in the human. When CP was incubated with MG, the protein showed increased electrophoretic mobility which represented the aggregates at a high concentration of MG (100 mM). MG-mediated CP aggregation led to the loss of enzymatic activity and the release of copper ions from the protein. Radical scavengers and copper ion chelators significantly prevented CP aggregation. CP is an important protein that circulates in plasma as a major copper transport protein. It is suggested that oxidative damage of CP by MG may induce perturbations of the copper transport system and subsequently lead to harmful intracellular condition. The proposed mechanism, in part, may provide an explanation for the deterioration of organs in the diabetic patient.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.279-279
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• 1994

Fibrinolytic proteases, piscivorase I (PI) and piscivorase II (PII), were isolated from Agkistrodon piscivorus piscivorus (eastern cotonmouth moccasin) venom using gel filtration on Bio-Gel P100 and ion-exchange chromatography on CM-Sepharose. The molecular welghts of two proteases were approximately 23400 and 29000. Their isoelectric points 6.6 and 8.5, respectively. The partial amino acid sequences of PI were characterized by tryptic digestion. PI readily cleaves the A${\alpha}$-and B${\beta}$-chaln of fibronogen, but PII rapidly cleaves A${\alpha}$-chain and more slowly the B${\beta}$-chain, They were activated by Ca$\^$2+/, Mg$\^$2+/ and Ba$\^$2+/, but inhibited by Zn$\^$2+/, Cu$\^$2+/ and Mn$\^$2+/. Two enzymes were also inhibited by cysten, ${\beta}$-mercapto -ethanol, and by metal chelators such as EDTA and EGTA, but not by benzamidine, PMSF, soybean trypsin inhibitor and aprotinin. They did not act like thrombin, plasmin and kallikrein, using specific chromogenllc substrates. Two protease did not induce platelet aggregation. PI showed low hemorrhagic activity at dosage of 50 $\mu\textrm{g}$.

• Journal of Korean Ophthalmic Optics Society
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• v.1 no.1
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• pp.115-118
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• 1996

The study on the cytotoxicities of heavy metals, metal-metal and metal-chelator combinations was carried out to evaluate the cytotoxic effect of those on mouse L929 fibroblasts. The colorimetric assays (NR and MTT) were conveniently carried out in 96-well microtiter plates. The rank order was Cd > Zn Ni > Cr(III) for the heavy metals tested. Examination of the effect of metal-metal interaction on cytotoxicity showed a moderate reduction of cadmium toxicity by zinc. The colorimetric assays were also effectively used to investigate the effect of the chelators, ethylenediamine tetra acetic acid (EDTA) and chitosan. Reduction of heavy metal toxixity by chelator was efficient.

• BMB Reports
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• v.46 no.11
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• pp.555-560
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• 2013

Acrolein is the most reactive aldehydic product of lipid peroxidation and is found to be elevated in the brain when oxidative stress is high. The effects of acrolein on the structure and function of human Cu,Zn-superoxide dismutase (SOD) were examined. When Cu,Zn-SOD was incubated with acrolein, the covalent crosslinking of the protein was increased, and the loss of enzymatic activity was increased in a dose-dependent manner. Reactive oxygen species (ROS) scavengers and copper chelators inhibited the acrolein-mediated Cu,Zn-SOD modification and the formation of carbonyl compound. The present study shows that ROS may play a critical role in acrolein-induced Cu,Zn-SOD modification and inactivation. When Cu,Zn-SOD that has been exposed to acrolein was subsequently analyzed by amino acid analysis, serine, histidine, arginine, threonine and lysine residues were particularly sensitive. It is suggested that the modification and inactivation of Cu,Zn-SOD by acrolein could be produced by more oxidative cell environments.

• The Korean Journal of Nuclear Medicine
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• v.38 no.2
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• pp.190-197
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• 2004

Apoptosis plays a role in the pathophysiology of many kinds of diseases and in the response of treatment. Compared to the necrosis, the apoptosis is a genetically controlled and energy-dependent process which removes the unwanted cells from the body; programmed cell death or cell suicide. During the apoptosis, phosphatidylserine is expressed in the cytoplasmic outer membrane in the early phase. Annexin V, an endogenous human protein (MW=35 kD), has an affinity of about $10^{-9}\;M$ for the phosphatidylserine exposed on the outer membrane of apoptotic cells. Annexin V can be radiolabeled with $^{99m}Tc$ by HYNIC or EC chelators, which can be used as an radiotracer for the in vivo imaging of apoptosis. In this article, we reviewed the apoptosis, radiolabeling of annexin V, and the experimental and clinical data using annexin V imaging.