The enzymatic mechanisms in accumulation of AGEs and its regulation by flavonoids
| Project/Area Number |
14560090
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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 |
食品科学・栄養科学
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| Research Institution | Iwate University |
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Principal Investigator |
NAGSAWA Takashi Iwate University, Faculty of Agriculture, Associate professor, 農学部, 助教授 (80189117)
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| Co-Investigator(Kenkyū-buntansha) |
ITO Yosiaki Iwate University, Faculty of Agriculture, Assistant Professor, 農学部, 助手 (50312517)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | glycation / flavonoids / aldose reductase / glyoxalase / proteasome / diabetes / AGE / ユビキチン / ラット / α-ジカルボニル化合物 |
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| Research Abstract |
We investigated that flabonoids shows inhibition of glycation using rut in and flavonoids rich extract from wild grape. N_ε-fructoselysine contents of skeletal muscle, kidney and serum proteins markedly increased in streptozotocin-induced diabetic rats. 0.2% rutin supplemented diet suppressed these increases. Furthermore, the increased AGE contents in diabetic rats were also inhibited by dietary rutin. Dietary wild grape extract suppressed AGE content in kidney and serum protein in the same extent of dietary rutin. These results suggested that flavonoids have effects of inhibition in many steps in glycation reaction.
The increased α-dicarbonyl compounds content in liver of streptozotocin-induced diabetic rats was decreased by feeding of rutin and wild grape extract supplemented diet. The increased activity in aldose reductase, the rate-limiting enzyme in the production of α-dicarbonyl compounds in diabetic rats was attenuated by feeding of these flavonoids supplemented diet. In vitro experiment showed that rutin and quercetin inhibited the activity of aldose reductase. On the other hand, the activity of glyoxalase, a decomposing enzyme against α-dicarbonyl compounds reduced in diabetic rats. The activity of glyoxalase was inhibited by wild grape extract in vitro, but not in vivo.
Proteasome activity itself was more resistant against glycation than other enzymes. Oxidatively modified proteins are easily degraded by proteasome. Although AGE proteins were ubiquitinated, degradation of these proteins were not increased. These results suggested that highly aggregated proteins by glycation are not degraded by proteasome and the AGE accumulates in the cell.
Thus, the production of AGE is necessary in the action of enzymes, and these enzyme actions may regulate by dietary fravonoids.
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Report
(4 results)
Research Products
(5 results)
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[Publications] Nagasawa, T., Tabata, N., lto, Y., Aiba, Y., Nishizawa, N., Kitts, D.D.: "Dietary G-rutin suppresses glycation in tissue proteins of streptozotocin-induced diabetic rats"Molecular and Cellular Biochemistry. (発表予定). (2003)
