1999 Fiscal Year Final Research Report Summary
Polymorphism in the promoter and coding regions of human metallothionein IIA gene
| Project/Area Number |
10558090
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
環境影響評価(含放射線生物学)
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| Research Institution | St. Marianna University |
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Principal Investigator |
YOSHIDA Minoru St.Marianna University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (80081660)
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| Co-Investigator(Kenkyū-buntansha) |
NAGANUMA Akira Tohoku University, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究科, 教授 (80155952)
YAMAZAKI Kentarou St.Marianna University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (80220309)
NAKADA Konosuke St.Marianna University, Faculty of Medicine, Professor, 医学部, 教授 (70081734)
IDE Tsuyoshi Kumamoto Immunochemical Laboratory, President, 代表取締役
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| Project Period (FY) |
1998 – 1999
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| Keywords | Mtallothionein / Kidney / Cadmium / Polymorphism / Promoter / Renal injury |
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| Research Abstract |
Cadmium concentration in the human tissues increase with aging because most of the accumulated cadmium may be remained in the bodies without excreting. General Japanese usually well eat rice which naturally containing relatively high concentration of cadmium. On the other hand, cadmium has been known to induce synthesis of metallothionein, a mental binding protein which reduces toxicity of heavy metals. In the general adults, most of cadmium accumulated in the tissues exist as low toxic complex with matallothionein. We found some Japanese adults whose kidneys have relatively low concentration of metallothionein. There is a possibility that the "low metallothionein" may be induced by genetic disorder. Therefore, we examined abnormality of nucleotide sequence of metallothionein gene and its promoter region of general Japanese by single-stranded conformation polymorphism method(PCR-SSCP). Genomic DNA samples were extracted from cortex of kidney of the forensic autopsy samples(21 examples). By PCR-SSCP and direct sequencing methods, abnormalities of nucleotide sequence of metallothionein gene and its promoter region were observed in some samples. Single base substitutions were found in the promoter region of four samples and in the exon 3 of two samples. The substitution(A->G) in the promoter region in all four samples was observed in 5 bases upstream from the transcription starting point. On the other hand, the mutation(GCC->GTC) of exon 3 was observed in the same site of the two samples, inducing the amino acid substitution of Ala->Val. In one sample, these two substitutions was observed in identical allele of promoter and exon 3. Effect of these base substitutions on the synthesis of metallothionein will be examined in future.
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Research Products
(12 results)
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[Publications] Yoshida,M., Satoh,M., Shimada,A., Yasutake,A., Sumi,Y., and Tohyama,C.: "Pulmonary toxicity caused by acute exposure to mercury vapor is enhanced in metallothionein-null mice."Life Sci.. 64. 1864-1867 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Yoshida,M., Satoh,M., Shimada,A., Yasutake,A., Sumi,Y., and Toyama,C.: "Distribution and retention of mercury in metallothionein-null mice after exposure to mercury vapor."Toxicology. 139. 129-136 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Asahi,I., Miura,N., Yamabe,Y., Toyoda,H., Imura,N., Koyama,M. and Naganuma,A.: "PF1070A, a novel and potent inducer of the synthesis of metallothionein."Biochemistry. 38. 10415-10423 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Yoshida,M., Ohta,H., Yamauchi,Y., Seki,Y., Sagi,M., Yamazaki,K., Sumi,Y.: "Age-dependent changes in metallothionein levels in liver and kidney of the Japanese"Biol.Trace Elem.Res. 63. 167-175 (1998)
Description
「研究成果報告書概要(欧文)」より
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