Carnosine Facilitates Nitric Oxide Production in Endothelial F-2 Cells
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- Takahashi Satoru
- First Department of Biochemistry, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare
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- Nakashima Yukiko
- First Department of Biochemistry, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare
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- Toda Ken-ichi
- Department of Dermatology, The Tazuke Kofukai Medical Institute, Kitano Hospital
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Abstract
We examined the effect of carnosine (β-alanyl-histidine) on nitric oxide (NO) production and endothelial NO synthase (eNOS) activation in endothelial F-2 cells. Carnosine enhanced NO production in a dose-dependent manner, and the stimulatory effect of carnosine was observed at concentrations exceeding 5 mM. The carnosine-stimulated NO production was inhibited by NG-nitro-L-arginine methyl ester, but not by NG-nitro-D-arginine methyl ester. In contrast, β-alanine, histidine (carnosine components) and anserine (N-methyl carnosine) failed to increase NO production. Carnosine had no effect on NO production for the initial 5 min, but thereafter resulted in a gradual increase in NO production up to 15 min. Carnosine did not induce phosphorylation of eNOS at Ser1177. The carnosine-induced increase in NO production was observed even when extracellular Ca2+ was depleted by ethylene glycol bis(2-aminoethyl ether)-N,N,N′-N′-tetraacetic acid however, the effect was abolished upon depletion of intracellular Ca2+ by BAPTA. After F-2 cells were incubated with carnosine for 4 min, intracellular Ca2+ concentration gradually increased. The carnosine-induced increase in intracellular Ca2+ concentration occurred even in the absence of extracellular Ca2+. These results indicate that carnosine facilitates NO production in endothelial F-2 cells. It is also suggested that eNOS is activated by Ca2+, which might be released from intracellular Ca2+ stores in response to carnosine.
Journal
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- Biological and Pharmaceutical Bulletin
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Biological and Pharmaceutical Bulletin 32 (11), 1836-1839, 2009
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390001204624485376
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- NII Article ID
- 130000116953
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- NII Book ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL BIB ID
- 10412757
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- PubMed
- 19881293
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed