1996 Fiscal Year Final Research Report Summary
REGULATION OF ZINC PROTEINS AND CELLULAR ZINC HOMEOSTASIS
| Project/Area Number |
07457541
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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 | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | FACULTY OF PHARMACEUTICAL SCIENCES,KYUSHU UNIVERSITY |
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Principal Investigator |
OGURI Kazuta KYUSHU UNIV., FAC.PHARM.SCI., PROFESSOR, 薬学部, 教授 (70037589)
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| Co-Investigator(Kenkyū-buntansha) |
ISHII Yuji KYUSHU UNIV., FAC.PHARM.SCI., INSTRUCTOR, 薬学部, 助手 (90253468)
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| Project Period (FY) |
1995 – 1996
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| Keywords | cytosol / aldolase / rat / alcohol dehydrogenase / triose phosphate / tyrosine phosphatase / carbonic anhydrase / polychlorinated biphenyl |
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| Research Abstract |
Toxic manifestation of coplanar PCB is thought to be mediated by aromatic hydrocarbon (Ah)-receptor. However, the suppression of protein expression by coplanar PCBs is scarcely clarified. We report here the suppression of cytosolic proteins by a coplanar PCB-treatment and propose new aspects of the toxicity. Male Wistar rats were treated with PenCB (single 25 mg/kg, i. p.). Free- and pair-fed control groups were treated with vehicle. At the day 5, the liver cytosol was prepared. The cytosolic proteins were compared among three groups by SDS-PAGE and two-dimensional RAGE (2D-PAGE). Expression level of cytosolic 40-kDa and 27-kDa proteins in rat liver were markedly suppressed by PenCB-treatment. The 40-kDa proteins were identified as aldolase B (Ald B) and alcohol dehydrogenase (ADH) class I by amino acid sequencing of the internal peptides. The 27-kDa protein was also identified as carbonic anhydrase III (CA II). The liver cytosolic Ald and ADH activities were significantly reduced to about 50% and 60% of both control groups by PenCB-treatment. Immunoblotting after sD-PAGE demonstrated that Ald B was markedly suppressed by PenCB-treatment, while change in Ald A was slight. The reduction of ADH by PenCB-treatment was also verified by immunoblotting. The significant suppression of CA III by PenCB-treatment in rat liver was demonstrated by immunoblotting using CA III-selective antibody. Ald plays an important role in glycolytic and gluconeogenetic pathways. In addition, ADH catalyzes biotransformation of triose phosphate to glycerol-3-phosphate. Sippression of Ald B and ADH may be a key biochemical lesion for disordered intermediary metabolism occurring by PenCB-treatment and should be taken into an account as a cause of the wasting syndrom which is a severe toxic effect of toxic coplanar PCBs. CA III possesses tyrosine phosphatase activity, therefore, its suppression could account for the effects on signal transduction by toxic coplanar PCBs.
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[Publications] Ishii, Y., Kato, H., Hatsumura, M., Ishida, T.Ariyoshi, N., Oguri, K.: "Significant suppression of rat liver aldolase B by a toxic coplanar polychlorinated biphenyl, 3,3', 4,4', 5-pentachlorobiphenyl" Toxicology. 116. 193-199 (1997)
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