2013 Fiscal Year Final Research Report
S-Nitrosated Alpha-1-acid Glycoprotein Kills Drug-resistant Bacteria and Aids Survival in Sepsis
| 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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| Project Period (FY) |
2012-04-01 – 2014-03-31
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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 |
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| 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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[Journal Article] S-nitrosatedα-1-acid glycoprotein kills drug-resistant bacteria and aids survival in sepsis2013
Author(s)
Watanabe K, Ishima Y, Akaike T, Sawa T, Kuroda T, Ogawa W, Watanabe H, Suenaga A, Kai T, Otagiri M, Maruyama T
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Journal Title
FASEB J
Volume: 27(1)
Pages: 391-8
DOI
Peer Reviewed
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[Journal Article] S-guanylation of human serum albumin is a unique posttranslational modification and results in a novel class of antibacterial agents2012
Author(s)
Ishima Y, Hoshino H, Shinagawa T, Watanabe K, Akaike T, Sawa T, Kragh-Hansen U, Kai T, Watanabe H, Maruyama T, Otagiri M
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Journal Title
J Pharm Sci
Volume: 101(9)
Pages: 3222-9
DOI
Peer Reviewed
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[Journal Article] Characterization of the hepatic cellular uptake ofα(1) -acid glycoprotein (AGP), part 1 : a peptide moiety of human AGP is recognized by the hemoglobinβ-chain on mouse liver parenchymal cells2012
Author(s)
Nishi K, Komori H, Kikuchi M, Uehara N, Fukunaga N, Matsumoto K, Watanabe H, Nakajou K, Misumi S, Suenaga A, Maruyama T, Otagiri M
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Journal Title
J Pharm Sci
Volume: 101(4)
Pages: 1599-606
DOI
Peer Reviewed
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[Presentation] S-nitrosated a-1-acid glycoprotein kills drug-resistant bacteria and aids survival in sepsis2013
Author(s)
Kaori Watanabe, Yu Ishima, Teruo Kuroda, Wakano Ogawa, Hiroshi Watanabe, Ayaka Suenaga, Toshiya Kai, Masaki Otagiri, and Toru Maruyama
Organizer
Asian Federation for Pharmaceutical Sciences 2013
Place of Presentation
Ramada Plaza Jeju Hotel, Jeju, Korea
Year and Date
20131121-22
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[Presentation] A human serum albumin–thioredoxin fusion protein prevents experimental contrast-induced nephropathy2013
Author(s)
Hiroshi Watanabe, Azusa Kodama, Ryota Tanaka, Hisae Tanaka, Victor Tuan Giam Chuang, Yu Ishima, Masafumi Fukagawa, Masaki Otagiri, Toru Maruyama
Organizer
Asian Federation for Pharmaceutical Sciences 2013
Place of Presentation
Ramada Plaza Jeju Hotel, Jeju, Korea
Year and Date
20131121-22
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