• Applied Microscopy
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• 제32권4호
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• pp.411-419
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• 2002

Metallothionein (MT) is a family of ubiquitous, low molecular weight ($6,000{\sim}7,000D$), cysteine-rich ($30{\sim}35%$) inducible protein with a high affinity to metal ions and has no aromatic amino acids and histidine. Some of the known functions of MT include detoxification of heavy metals and alkylating agents and neutralization of free radicals. Also, this protein has been reported to involve in tumor pathophysiology and therapy resistance. MT expression may affect a number of cellular processes including gene expression, apoptosis, proliferation and differentiation. Many reports on the physiological and biochemical properties of MT have been published, but ultrastructural reports on the localization of MT in human gastric cancer tissues are extremely rare. The present study was undertaken to examine the ultrastructural features and the localization of MT within the gastric adenocarcinoma. Ultrastructures of gastric cancer cells were characterized by the high nuclear cytoplasmic ratio, the interdigitation between cells, the irregular nucleus containing much heterochromatin and the wide distribution of free ribosomes in the cytoplasm. Immunohistochemical reaction for MT was prominent in the gastric adenocarcinoma. And the immunogold labellings were more prominent within the nucleus than the cytoplasm. Particularly, immunogold particles were numerously seen at nulcleolus or nucleolar associated heterochromatin. These results suggest that MT expression by gastric cancer cells is associated with cell proliferative activity and is possibly synthesized in the cytoplasm, and then the protein is transported into the nucleus to participate in any transcriptional steps.

• Tuberculosis and Respiratory Diseases
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• 제50권5호
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• pp.579-590
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• 2001

Background : The aging process may be induced, at least in part, by reactive oxygen species(ROS). It has been thought that the lung could be a good source of ROS because it has a high oxygen tension. In the present study, we invetigated the inducibility of the first and last lines against oxidative stress, superoxide dismutases(CujZn-SOD and Mn-SOD) as a scavenger of ${O_2}^-\;{\cdot}$ and metallothionein(MT) as a scavenger of $OH{\cdot}$, respectively, in mouse lungs with age. Methods : Oxidative stress was induced by paraquat, an intracellular superoxide generator, at 1, 4, 8, and 12 months of age and then SODs and MT mRNAs were determined by RT-PCR method. Results : The steady-state level of Mn-SOD mRNA increased from 1 to 8 months but decreased thereafter. However, Mn-SOD mRNA was not induced by paraquat after 1 month. On the other hand, there was no change in the steady-state level of Cu/Zn-SOD mRNA, which decreased abruptly at 12 months of age. Additionally, Cu/Zn-SOD mRNA was not induced by paraquat at any age. There was no change in the steady-state level of MT mRNA with age whereas its inducibility by paraquat was intact at all ages. Conclusion : These results indicate that lack of induction of SODs with age may be one of the causative factors in the aging process while induction of MT may play an important role in the defense against oxidative stress. It is therefore implicated that the tissue antioxidant/prooxidant balance could be one of determinants of mean life span.

• Proceedings of the Korean Society of Toxicology Conference
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• 한국독성학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.42-58
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• 2002

Acute Cd exposure produces hepatotoxicity, whereas chronic Cd exposure produces nephrotoxicity, hematotoxicity, immunotoxicity and bone damage. Previous experiments suggest that the low-molecular-weight, metal-binding protein metallothionein (MT) in liver protects against liver injury, but is responsible for the kidney injury observed after chronic Cd exposure.(omitted)

• Korean Journal of Environmental Biology
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• 제25권4호
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• pp.289-296
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• 2007

Di-(ethyhexyl) phthalate (DEHP), commonly used as a plasticizer for manufacturing flexible vinyl products, has been the topic of extensive research, especially concerning endocrine disrupting properties. Metallothionein (MT) is a low molecular weight (6,000$\sim$7,000 Da), cysteine-rich (22$\sim$23%), metal-binding protein and is known to be induced by extrinsic factors such as chemical agents and stresses. Some of the known function of MT include detoxification of heavy metals and alkylating agents and neutralization of free radicals. Nonetheless, the definitive physiological function of MT are still unknown. This study was carried out to investigate the effects of DEHP on the ultrastructural changes and the expression of MT of the rat liver. The rats were orally intubated with either corn oil (experimental control) or 0.5 mg, 1.5 mg and 4.5 mg DEHP kg$^{-1}$ day$^{-1}$ in 0.5 mL of corn oil for 15 days before sacrificing and sampling. DEHP induced mild ultrastrctural changes of some cell organelles such as rough endoplasmic reticulum, mitochondria, lysosomes and peroxisomes in the rat liver treated with DEHP. In the respect of immunogold labelling and Western blotting, MT expression of the liver tissue was up-regulated by DEHP. In conclusion, DEHP has effects on the ultrastructures and hepatic function for MT expression in rat.

• Journal of fish pathology
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• 제5권2호
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• pp.143-152
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• 1992

Metallothionein is an essential and common protein to regulate the intracellular concentration of heavy metals, which exist in most organisms from bacteria to vertebrates. Although the detailed function of metallothianein has not been fully identified until yet, it may be involoved in the cellular protection against the heavy metal toxicity and in the global regulation of several other genes and the expression of metalloproteins. We have cloned the full cDNA clone of metallothionein gene in Channel Catfish by Reverse Transcriptase-Polymerase Chain Reaction(RT-PCR) starting from poly(A)-containing mRNAs. All PCR fragments have been subcloned into EcoRV site of pBluescript SK+ and dT-tailed at Smal site of pUC19, then PCR products are recovered by the double digestion of recombinant plasmids wiht EcoRI and HindIII, which are adjacent to EcoRV site in multicloning sites or by rapid PCR screening. The nucleotide sequence analysis of pMT150(one of the PCR clones) showed high homology with several other piscine metallothionein cDNA genes.

• Proceedings of the Korean Environmental Health Society Conference
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• 한국환경보건학회 2002년도 춘계 국제 학술대회
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• pp.47-48
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• 2002

The purpose of this study was to investigate the metallothionein of acute cadmium poisoning mice as a Cadmium index. Forty male ICR mice were injected with cadmium chloride solution from 1/8LD$\sub$50/ to 1/2 LD$\sub$50/ dose. At 24 hours after exposed Cd, I examined Cd and metallothionein (MT) in tissues (liver and kidney) and fluids (whole blood and urine) and also measured low molecular proteins, N-acety1-${\beta}$-D-glucosaminidase (NAG) and ${\beta}$$\sub$2/- microglobuline (${\beta}$$\sub$2 /-MG) in urine. The concentration of Cd and MT of liver, kidney whole blood and urine were increased with dose dependent manner. Urinary Cd and urinary MT had very good significance (p＜0.01) and urinary MT had good significance with kidney Cd and NAG but not ${\beta}$$\sub$2/-MG. Conclusionally MT in urine was very correlated with kidney Cd and urine Cd. So MT maybe useful as a Cd poisoning index.

• Animal cells and systems
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• 제2권2호
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• pp.269-275
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• 1998

The reporter plasmid pMT-lacZ containing the metallothionein (MT) promoter region (-320∼+58 with respect to the transcription initiation site) fused to the lacZ gene in a P-element vector was constructed. Transgenic Drosophila bearing the MT-lacZ fusion gene were established by P-element mediated transformation. Expression of the MT-lacZ fusion gene in transformants was examined during development. By treatment with low concentration of cadmium (>1O uM) or paraquat (>50 uM), increased expression of B-galactosidase was shown in fat body, brain lobe, and ganglion transgenic larval tissues. The results show that transformants bearing the MT-lacZ fusion gene are useful for further studies on the mechanism of regulation of MT gene expression and for monitoring toxic metals.

• Applied Microscopy
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• 제35권1호
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• pp.15-22
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• 2005

Metallothionein (MT) is a low molecular weight, cysteine-rich, metal-binding, and non-enzymatic protein. The present study was carried out to investigate the expression of MT gene as well as the localization of MT in regenerating rat liver. In partial hepatectomized rats, MT mRNA was detected as early as 1 hr and reached a maximal level by 8 hr after the operation. Thereafter, this level decreased gradually until 24 hr, and it became similar to that of sham control. Meanwhile, time course of MT immunoreactivity using immunogold-labelling revealed that the number of gold particles in hepatocytes increased significantly by 12 hr, but decreased at 48 hr after partial hepatectomy. Ultrastructurally, immunogold particles indicating the presence of MT were distributed in both the cytoplasm and the nucleus of the rat hepatocytes, particularly the particles were distributed at rough endoplasmic reticulum and nucleolus and did not seem to adhere to mitochondria or lysosomes in proliferating hepatocytes. Briefly, high level of MT mRNA expression and the intense immunoreactivity and/or the specific localization of MT was observed during liver regeneration. These results suggest that MT possibly involves hepatocyte proliferation via the storage or the supply of various metal ions in the regenerating rat liver.

• Toxicological Research
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• 제11권2호
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• pp.223-227
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• 1995

This study was conducted to investigate the metallothionein (MT) induction by Lonicerae rios in cadmium chloride intoxication. The results were as follows: Generally, detoxication effects by Lonicerae fios extract increased to the increase of extract concentrations. When 90 mg/kg dosage of Lonicerae fios extract was administered, it showed the highest antitoxic effects in metallothionein induction. From the above results, Lonicerae rios extract increased metallothionein concentration and decreased the toxicity of cadmium in liver.

• Environmental Analysis Health and Toxicology
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• 제19권2호
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• pp.191-200
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• 2004

Zinc (Zn) is an essential element in biological process, however inadequate Zn status in general population have been recognized. To update the knowledge for Zn-cadmium (Cd) interaction, we studied the intestinal uptake and transport, and the expression of metal transporter proteins (divalent metal transporter 1, DMT1 ; metal transporter protein 1, MTP1 ; zinc transporter 1, ZnTl ; metallothionein 1 , MT1) in duodenum after Cd exposure using Zn deficient animal model. Rats were led Zn deficient (ZnD, 0.5-1.0 mgZn/kg) or Zn supplemented (ZnS, 50mg Zn/kg) diet for 4 weeks, and followed single administration of $^{109}$ CdCl$_2$orally. The body Zn flatus and tissue Cd concentration were determined at 24 hrs after Cd administration. Total body burden of Cd and Cd absorption index (AI, %) were estimated based on the tissue Cd analyzed. DMT1, MTP1, ZnTl and MT1 mRNA were analyzed by using RT-PCR method. Feeding of Zn deficient diet for 4 weeks produced a reduced body weight gain and a depletion of body Zn. Tissue Cd concentration, body burden of Cd and Cd absorption index were higher in the ZnD diet fed rats than the ZnS diet red rats. Especially, Cd concentration in the small intestine (duodenum, jejunum and ileum) and the colon of FeD diet fed rats were higher markedly than in the FeS diet group. The expression levels of DMT1, MTP1 and ZnT1 mRNA in FeD diet fed rats were similar to the FeS diet. The level of MT1 mRNA expression was significantly lower in the FeD than the FeS diet fed rats. Taken together, theses results indicate that Zn deficiency in diet induce an increased intestinal absorption and tissue retention of Cd, and down -regulate the MT1 expression in the intestine which might be play a part of role in Cd absorption and transport in mammalian. These findings suggest that deficiency of essential metal could be enhanced the toxicity of toxic, non-esstial metals through the metal-metal interaction.