Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 배옥남 | - |
dc.date.accessioned | 2018-11-08T02:11:47Z | - |
dc.date.available | 2018-11-08T02:11:47Z | - |
dc.date.issued | 2008-04 | - |
dc.identifier.citation | TOXICOLOGICAL SCIENCES, v. 103, No. 1, Page. 181-190 | en_US |
dc.identifier.issn | 1096-6080 | - |
dc.identifier.uri | https://academic.oup.com/toxsci/article/103/1/181/1695187 | - |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/80292 | - |
dc.description.abstract | U-shaped response has been frequently encountered in various biological areas including epidemiology, toxicology, and oncology. Despite its frequent observation, the theory of U-shaped response has been crippled by the lack of a robust mechanism underlying and incomplete in vitro and in vivo correlation. In the present study, a novel mechanism is provided for a U-shaped response, based on the findings of agonist-induced vasomotor tone change affected by menadione (MEN) (synthetic vitamin K-3), a reactive oxygen species generator, and arsenic, an environmental pollutant, which showed typical U-shaped responses in both in vitro aortic contractile response and in vivo blood pressure. U-shaped responses by MEN and arsenic were a combined result from heterogenic susceptibilities and responses of multiple target cells composing blood vessels, that is, endothelium and smooth muscle. Notably, endothelium, a regulator of vasomotor tone, was primarily affected by low-dose stimuli, whereas smooth muscle, an effector of vascular contraction, was affected later by high-dose. The dysfunction of smooth muscle was produced by high-dose MEN-induced hydrogen peroxide, resulting in the attenuation of vascular contractile reactivity, whereas low-dose MEN-induced superoxide led to the quenching of vasodilatory nitric oxide in endothelial cells, resulting in the enhancement of vasoconstriction. This mechanistic theory, the difference in susceptibilities and responses to a common stimulus between regulator and effector components of a system, could give a new insight into the explanation of various U-shaped responses and provide a new evidence for the need of the risk assessment of toxicants with a wider dose range. | en_US |
dc.description.sponsorship | Eco-Technopia 21 project of the Ministry of Environment; and National Institute of Toxicological Research project from Korea Food Drug Administration. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | OXFORD UNIV PRESS | en_US |
dc.subject | U-shaped dose response | en_US |
dc.subject | vasoconstriction | en_US |
dc.subject | arsenic | en_US |
dc.subject | menadione | en_US |
dc.subject | endothelial cells | en_US |
dc.subject | smooth muscle cells | en_US |
dc.subject | heterogenic responses | en_US |
dc.subject | risk assessment | en_US |
dc.title | U-shaped dose response in vasomotor tone: A mixed result of heterogenic response of multiple cells to xenobiotics | en_US |
dc.type | Article | en_US |
dc.relation.volume | 103 | - |
dc.identifier.doi | 10.1093/toxsci/kfn023 | - |
dc.relation.page | 181-190 | - |
dc.relation.journal | TOXICOLOGICAL SCIENCES | - |
dc.contributor.googleauthor | Bae, Ok-Nam | - |
dc.contributor.googleauthor | Lim, Kyung-Min | - |
dc.contributor.googleauthor | Han, Jee-Yeon | - |
dc.contributor.googleauthor | Jung, Byoung-In | - |
dc.contributor.googleauthor | Lee, Jin-Young | - |
dc.contributor.googleauthor | Noh, Ji-Yoon | - |
dc.contributor.googleauthor | Chung, Seung-Min | - |
dc.contributor.googleauthor | Lee, Moo-Yeol | - |
dc.contributor.googleauthor | Lee, Joo-Young | - |
dc.contributor.googleauthor | Chung, Jin-Ho | - |
dc.relation.code | 2008209517 | - |
dc.sector.campus | E | - |
dc.sector.daehak | COLLEGE OF PHARMACY[E] | - |
dc.sector.department | DEPARTMENT OF PHARMACY | - |
dc.identifier.pid | onbae | - |
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