Studies on Prolidase Deficiency - Effect of Iminodipeptides on Collagen Metabolism
Project/Area Number |
62570454
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Research Category |
Grant-in-Aid for General Scientific Research (C)
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Allocation Type | Single-year Grants |
Research Field |
Dermatology
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Research Institution | Okayama University Medical School (1988) Kochi Medical School (1987) |
Principal Investigator |
ARATA Jiro Department of Dermatology, 医学部, 教授 (70033082)
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Project Period (FY) |
1987 – 1988
|
Project Status |
Completed (Fiscal Year 1988)
|
Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1988: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1987: ¥1,200,000 (Direct Cost: ¥1,200,000)
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Keywords | Prolidase deficiency / Prolidase isozyme / Fibroblast / Wound healing / Mouse epidermis / 基質特異性 / 2価イオン / アイソザイム / 症状発現 / 遊離アミノ酸 / プロリダーゼ / プロリールハイドロキシレース |
Research Abstract |
1) The prolidase(PD) activities of cultured skin fibroblasts derived from prolidase deficient sisters, the elder with typical clinical manifestations and the younger with only slight clinical manifestations were examined biochemically. 2) Isozymes of prolidase(PD-I,II) from cultured human skin fibroblasts were separated by DESE-5PW column HPLC. 3) PD activities in rat skin during wound healing were studied. 4) PD activities in an extract of newborn mouse epidermis were examined. Results 1) PD activities against several substrates other than Gly-Pro were present to some degree in both sisters. There were no detectable differences in PD activity between symptom(+) patients and the symptom(-) sister with respect to the effect of divalent cations and the substrate specificity. 2) In control, activities of PD-1 were decreased in the descending order of activities against Gly-Pro, Ala-Pro, Met-Pro. However, activities of PD-II were decreased in the descending order of activities against Met-
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Pro, Gly-Pro, Ala-Pro. In prolidase deficient sisters, the activities of PD-I could not be detected, while the activities of PD-II were present. No remarkable differences were seen between the substrate specificities of the PD-II from symptom(+) patient and symptom(-) sister. 3) PD activities in rat skin adjacent to the wound were decreased at day 1 and gradually increased to about three times those of controls at day 14. 4) PD activities were detected in newdorn mouse epidermis. Mn^<2+> had a potent activating effect. Discussion 1) In this study, we estimated PD activity in cultured skin fibroblasts derived from a symptom(+) patient, her symptom(-) sister and controls. PD activities against substrates other than Gly-Pro were present to some degree in both patients in crude fibroblas extract. This indicates that PD was not absent but altered. 2) Recently, two forms of PD have been separated from human cells and various tissues. In our patients, activity of PD-I could not be determined in both sisters,while activity of PD-II present. The studies of substrate specificity using partially purified PD-II showed on differences between symptom(+) patient and symptom(-) sister. 3) The activities of PD adjacent to the wound were elevated at 14 days after injury. The local supply of amino acids produced by increased PD activity may compensate to some extent for amino acids used for synthesis of new collagen in wound healing. The relation of the dysfunction of the PD to the pathogenesis of the wound healing is unclear. However, insufficient recycling of endogenous free proline might cause delay in wound healing. 4) The existence of PD activities in the epidermis may suggest a possible involvement of PD in epitheilialization. In these contexts effect of iminodipeptides on collagen metabolism will be investigated. Less
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Report
(3 results)
Research Products
(2 results)