| Project/Area Number |
24659076
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Medical pharmacy
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
小田切 優樹 崇城大学, 薬学部, 教授 (80120145)
異島 優 熊本大学, 薬学部, 助教 (00457590)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | alpha-1酸性糖タンパク質 / 一酸化窒素 / 多剤耐性 / 抗菌活性 / α１－酸性糖タンパク質 |
|---|
| Research Abstract |
Treating infections with exogenous NO, with broad-spectrum antimicrobial activity, seems to be effective. Similar to NO biosynthesis, biosynthesis of alpha-1-acid glycoprotein variant A (AGPa), with a reduced cysteine, increases markedly during inflammation and infection. The purpose of this study was to determine whether S-nitrosated AGPa (SNO-AGPa) may be the first compound of this novel antibacterial class against multidrug-resistant bacteria. AGPa was incubated with activated RAW264.7 cells. Results indicated that endogenous NO generated by activated RAW264.7 cells caused S-nitrosation of AGPa at Cys149. SNO-AGPa strongly inhibited growth of Gram-positive, Gram-negative, and multidrug-resistant bacteria and was an extremely potent bacteriostatic compound. Treatment with SNO-AGPa markedly reduced bacterial counts in blood and liver in a mouse sepsis model. The sialyl residues of AGPa seem to suppress the antibacterial activity, since SNO-asialo AGPa was more potent than SNO-AGPa.
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