| Project/Area Number |
08044318
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | School of Medicine, Keio University |
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Principal Investigator |
SUEMATSU Makoto Associate Prof, Dept Biochem, Keio Univ., 医学部, 助教授 (00206385)
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| Co-Investigator(Kenkyū-buntansha) |
YONETANI Takashi Prof, Dept Biochem Biophys, Univ.Pennsylvania, 医学部, 教授
WILSON David F Prof, Dept Biochem Biophys, Univ.Pennsylvania, 医学部, 教授
ISHIMURA Yuzuru Prof & Head, Dept Biochem, Keio Univ., 医学部, 教授 (40025599)
EGAWA Tsuyoshi Instructor, Dept Biochem, Keio Univ, 医学部, 助手 (10232935)
WAKABAYASHI Yoshiyuki Instructor, Dept Biochem, Keio Univ, 医学部, 助手 (10276214)
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| Project Period (FY) |
1996
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| Keywords | Carbon monoxide / Nitric oxide / heme oxygenase / microcirculation / Liver / Bilirubin / Bile transport / oxidative stress |
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| Research Abstract |
Gaseous monoxides such as nitric oxide (NO) and carbon monoxide (CO) have recently attracted great interests as a regulator of cell and organ function. When exposed to endotoxin, cytokines or lschemia-reperfusion, the liver produces larger amounts of NO than those in the control via the activity of inducible NO synthase which can alter a variety of the organ function such as the sensitivity of vascular tone to catecholamine, mitochondrial membrane potential, biliary transport and tissue regeneration. On the other hand, the liver constitutively produces CO through the reaction of heme oxygenase. CO generated in the liver tissue can reach sinusoidal vessels and relax fat-storing Ito cells-the liver specific microvascular pericytes covering the sinusoidal wall-and thereby serves as an endogenous modulator of vascular tone. Two isoforms of the CO-generating enzyme have been characterized : heme oxygenase-1 which is inducible by a variety of stressors, and heme oxygenase-2 which constitutes the major enzyme activity under physiological conditions in the liver. Although it is still unknown whether excessive CO generation by the Inducible heme oxygenase activity may preserve or jeopardize the integrity of microvascular function in the liver, the potential importance of this double-edged molecule has just emerged much like nitric oxide, another gaseous molecule that was established as a neurovascular mediator inducing vascular cell relaxation. This manuscript provides an overview of the pathophysiological roles of these gaseous monoxides in regulation of microvascular function in the liver.
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