| Project/Area Number |
11671229
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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 |
Digestive surgery
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| Research Institution | AICHI MEDICAL UNIVERSITY |
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Principal Investigator |
NONAMI Toshiaki Faculty of medicine, Aichi Medical University, Associate Professor, 医学部, 助教授 (80189422)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMOMURA Yoshiharu Department Bioscience, Nagoya Institute of Technology, Professor, 工学部, 教授 (30162738)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Human liver / Mitochondoria / Pyruvate dehydrogenase / PDH kinase / Methacrylyl-CoA hydratase / β-hydroxyisobutyryl-CoA hydralase / Liver disease / Mito chondria / Pyruvate dehycrogenase / Methacrylyl-CoA hyclratase / β-hyctronyisobutyryl-CoA hyclrolase / Liver diseases / Liver / mitochondria |
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| Research Abstract |
Pyruvate dehydrogenase kinase (PDK) inactivates pyruvate dehydrogenase complex (PDC) by phosphorylation of one of the subunits of the complex and therefore plays an important role in regulation of glucose oxidation. Recent studies have demonstrated the existence of four isoenzymes of PDK, PDK1-4. In the present study, we examined the abundance of mRNAs for four isoenzymes of PDK in apparently normal human liver, and human livers with cirrhosis and hepatocellular carcinoma (HCC). We also studied the activities and mRNA expression levels of the enzymes related to valine catabolism Methacrylyl-coenzyme A (MC-CoA) hydratase and β-hydroxyisobutyryl-coenzyme A (HIB-CoA) in these livers.
The mRNAs were determined by quantitative polymerase chain reaction coupled with reverse transcription (RT-PCR). The mRNAs for PDK1, PDK2, and PDK4, but not PDK3, were detected in the human livers by the RT-PCR method. The abundance of PDK mRNAs in the normal liver was in order of PDK1<PDK2<PDK4. The level of
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PDK1 mRNA was significantly lower than that of PDK4 mRNA in the normal liver (p<0.01). In the livers with cirrhosis and HCC, the abundance of mRNAs for the PDK isozymes showed the same patterns as in the normal liver, and that for PDK2 and PDK4 tended to be decreased by chrhosis and HCC.The activities of both enzymes related to valine catabolism were significantly lower by 36-46% in the livers with cirrhosis and hepatocellular carcinoma than in the normal liver, suggesting that the decrease in capability to detoxify MC-CoA may be associated with the diseases. The mRNA levels for these enzymes measured by quantitative polymerase chain reaction were significantly increased in the cirrhotic liver, but were not altered in the livers with chronic hepatitis and hepatocellular carcinoma compared with those in the normal liver.
The decrease of PDK2 and PDK4 may be one of the causes of abnormal metabolism of glucose in the liver with cirrhosis and HCC.We also concluded that the low level of valine enzyme activities in the livers with cirrhosis and HCC are the results from post-transcriptional regulation of the enzymes in the damaged tissue. Less
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