| Project/Area Number |
63470108
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
応用生物化学・栄養化学
|
|---|
| Research Institution | Nagoya University |
|---|
Principal Investigator |
YOSHIDA Akira Dept. of Agricultural Chemistry Nagoya University, Professor, 農学部, 教授 (70035377)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ODA Hiroaki Dept. of Agricultural Chemistry Nagoya University, Assistant, 農学部, 助手 (20204208)
HORIO Fumihiko Dept. of Agricultural Chemistry Nagoya University, Assistant, 農学部, 助手 (20165591)
|
|---|
| Project Period (FY) |
1989 – 1990
|
| Project Status |
Completed (Fiscal Year 1990)
|
| Budget Amount *help |
¥8,800,000 (Direct Cost: ¥8,800,000)
Fiscal Year 1990: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1989: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1988: ¥4,700,000 (Direct Cost: ¥4,700,000)
|
|---|
| Keywords | xenobiotics / cytochrome P450 / ascorbic acid / cholesterol / apo P450 mRNA / 変異原物質 / ゼノバイオティクス(生体異物) / 血清コレステロ-ル / ビタミンC / 培養肝細胞 / アポリポタンパクA-I / HDL-コレステロ-ル / PCB / 血小板凝集 / フラビン含有モノオキシゲナーゼ / コレステロール |
|---|
| Research Abstract |
In our industrialized society, we have many chances to take synthetic organic chemicals as the environmental chemicals and drugs. The use of drugs would be increased in the high aged society as in Japan. These fat soluble synthetic organic chemicals are generally metabolized in Cytochrome P450 system in liver microsomes and called "xenobiotics".
Nutritional conditions affect significantly the metabolic systems of xenobiotics. Conversely, xenobiotics also affect the metabolism of nutrients. We have already reported that the various xenobiotics induced hypercholesterolemia. This hypercholesterolemia is characteristic for its elevation of serum level of High Density Lipoprotein (HDL) cholesterol. We investigated the changes in the pattern of apolipoprotein in detail and indicated the significant increase in apo A-I, which is a major apoprotein of HDL. Xenobiotics also increased the mRNA of apo A-I indicating the elevation of synthesis of apo A-I. Secretion of HDL from the liver was also increased by the treatment of xenobiotics. We also reported the HMG CoA reductase which is a rate limiting enzyme of cholesterol synthesis. These results indicate that xenobiotics increase the synthesis both cholesterol and apolipoproteins leading the increase in the serum level HDL-cholesterol.
Liver cytochrome P450 decreases in ascorbic acid deficient guinea pigs. We found the similar effect in ascorbic acid deficient ODS-rats which genetically can not synthesize ascorbic acid. Ascorbic acid deficiency didn't affect the heme synthesis but decreased the mRNA of apoproteins b and e of Cyt. P450, indicating apo cytochrome P450 synthesis is involved in the decrease in Cyt. P450 in ascorbic acid deficient ODS rat.
We also indicated the elevation of ascorbic acid synthesis due to xenobiotics in the primary cultured hepatocytes.
|
