| Project/Area Number |
15087212
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Science and Engineering
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| Research Institution | Yamagata Promotional Organization for Industrial Technology (2004-2006)
Yamagata Public Corporation For the Development Of Industry, Institute Life Support Technology (2003) |
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Principal Investigator |
YOSHIMURA Tetsuhiko (2005-2006) Yamagata Promotional Organization for Industrial Thchnology, Director General of Research and Development, 研究開発部, 部長 (70271517)
大矢 博昭 (2003-2004) 財団法人山形県産業技術振興機構, 生物ラジカル研究所, 副所長 (00025389)
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| Co-Investigator(Kenkyū-buntansha) |
OGATA Tateaki Yamagata University, Faculty of Engineering, Professor, 工学部, 教授 (50091830)
YOKOYAMA Hidekatsu Advanced Industrial Science and Technology Res. Inst. Instrumentation Frontier, Senior Research Scientist, 主任研究員 (10281619)
吉村 哲彦 (財)山形県産業技術振興機構, 生物ラジカル研究所, 副所長 (70271517)
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| Project Period (FY) |
2003 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥26,000,000 (Direct Cost: ¥26,000,000)
Fiscal Year 2006: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 2005: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2004: ¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 2003: ¥9,200,000 (Direct Cost: ¥9,200,000)
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| Keywords | nitric oxide (NO) / nitric oxide synthase (NOS) / lipopolysaccharide (LPS) / Helicobacter pylori / nitrate / gastro-esophageal junction / gastric mucosa / ESR / スピンプローブ法 / 植物 / ストレス応答機構 / オキシデイティブバースト / ジニトロシルジチオラト鉄錯体 / in vivo / サクラマス魚卵 / ストレス / 酸化還元状態 / in vivo ESR / 携帯型 / フリーラジカル / ストレス応答 / 植物用 / 誘導型NO合成酵素 / VCO / ダブルヘルムホルツコイル |
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| Research Abstract |
It is now recognized that nitric oxide (NO) is an endogenous mediator of vascular tone, a neurotransmitter in both the peripheral and central nervous systems, and an effector molecule in the immune system. NO is endogenously synthesized from L-arginine by NO synthases (NOSs), which exist in various organs and tissues in mammals. In the gastric mucosa, two types of constitutive NO synthases have been discovered and inducible NO synthase (iNOS), which is expressed in states of inflammation and immune activation, has not been detected in normal rat stomach. Additionally, a non-enzymatic NO production pathway appears to be active in the stomach, in which dietary nitrate is reduced to nitrite by the tongue surface bacteria and the nitrite is then carried into the stomach and reduced to NO under luminal acidic conditions. Endogenous NO, produced through these enzymatic and non-enzymatic pathways, has been demonstrated to be involved not only in the regulation of gastric mucosal blood flow, b
… More
ut also in the modulation of acid secretion, mucus secretion and gastric motility. In the present study, to elucidate physiological or pathophysiological roles of NO in stomach, we were carried out in vivo study by employing an animal model in which high concentration of NO were generated luminally at the gastro-esophageal junction by administration of nitrite plus acidic ascorbic acid, in vivo study on cross talk between iNOS and cyclooxygenase (COX) in rat gastric mucosa, and in vitro study on the effect of Helicobacter pylori (H. pylori)・lipopolysaccharide (LPS) on the expression of Toll-like receptor (TLR)2 and TLR4 using a mouse normal gastric epithelial cell line (GSM06). Consequently, we obtained following findings : 1) NO generated by nitrite administration on the lumen diffuses into the adjacent gastric tissue to a substantial degree, leading to localized consumption of glutathione in the tissue; 2) the effect of COX activity on iNOS-NO pathway can be important in the regulation of gastric mucosal integrity in inflammation states; 3) H. pylori-LPS stimulation induces TLR2 through TLR4 signaling in normal mouse gastric epithelial GSMO6 cells. This induced TLR2 cooperatively with TLR4 work for iNOS induction by H pylori-LPS simulation. Less
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