2003 Fiscal Year Final Research Report Summary
Relationship between transport mode and molecular structure in Na-HCO3 cotransporter
| Project/Area Number |
14571013
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SEKI George The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (30206619)
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| Co-Investigator(Kenkyū-buntansha) |
NOIRI Eisei The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (00301820)
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| Project Period (FY) |
2002 – 2003
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| Keywords | NBC1 / pRTA / pancreatic secretion / bicarbonate absorption / electrophysiology / cancer metastasis |
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| Research Abstract |
We tried to clarify the physiological and pathological significance of Na-11C03 cotransporter, NBC-1 Firstly, we identified several new NBC-1 mutations by screening cDNAs of patients having proximal renal tubular acidosis (pRTA). The data incated that NBC1 mutations identified so far locate in different regions in the NBC1 gene, and did not accumulate in the particular hot spots. By functional analysis on Xenopus oocytes, we showed that NBC1 function should be severely reduced (at least less than half of the wild-type activity) in order to induce proximal type acidosis. By immunohistochemical analysis using the vaiant specific antibodies, we showed that pancreatic variant (pNBC1) mediates bicarbonate secretion from pancreatic duct cells in both human and rat pancreas. It is suggested that functional loss of pNTBC1 may, via a similar mechanism as in cystic fibrosis, lead to pancreatic dysfunction. This hypothesis may be supported by high serum amylase levels found I pRTA patients. We also showed that kidney type variant (kNBC1) is expressed not only in the basolateral membrane of normal human kidney proximal tubules, but also in renal carcinoma tissues. NBC1 may be involved in metastasis of renal cell carcinoma (RCC). Since the prognosis of metastatic RCC is very poor, the future studies will be required to further clarify the roles of NBC1 in RCC.
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