| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Research Abstract |
Folate plays an important role in the biosynthesis of nucleic acids and amino acids. It has been known that folate deficiency induces the inhibition of cell proliferation, and the increase of homocysteine, which one of the risk factor of vascular diseases. In this study, we investigated the effect on vascular function and the regulatory mechanism of homocysteine, which is increased during folate deficiency.
The folate-deficient rats received an amino acid-defined, and folate-deficient diet. The control rats were fed the same diet supplemented with 8 mg/kg diet. The rats were killed by collecting the blood at the 4, 6, 8 weeks, and the liver and vessel was excised.
The concentrations of folate derivatives in plasma and liver of folate-deficient rats were significantly decreased. On the other hand, the concentrations of homocysteine on plasma and liver during folate deficiency were significantly increased. In vessel, the content of TBARS was increased, and the contents of glutathione and vitamin C were decreased. In folate-deficient rats, the concentration of nitric oxide (NO) in plasma was significantly decreased, and the protein of endothelial NO synthase was decreased by detection of western blotting. These results suggest that the increase of homocysteine during folate deficiency induced oxidative stress in vessel following dysfunction, which NO synthesis is deceased.
Secondly, it was examined that the change in gene expression of homocysteine metabolic enzymes during folate deficiency by real time RT-PCR method. In the folate-deficient rats, the levels of mRNA were significantly decreased in 5,10-methylelnetetrabhydrofolate reductase (MTHFR), methionine synthase (MS) and cystathionine-β-synthase (CBS), which are involved in the metabolism of homocysteine, compared to the control rats. These results suggest that the increase of homocysteine during folate deficiency is regulated by gene expressions of MTHFR, MS and CBS.
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