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疾患生命工学センター及びCNBI 共同セミナーのご案内です。

『Dioxin-Induced Hypoplastic Heart Failure and AHR Signaling in Zebrafish』

講師:Richard E. Peterson&s_comma; Ph.D.
School of Pharmacy and Molecular and Environmental Toxicology Center
University of Wisconsin&s_comma; Madison&s_comma; Wisconsin&s_comma; USA
疾患生命工学センター 客員教授

日時:2007年 9月13日(木)14:30 ~ 17:30

場所:医学部一号館 3階 講堂(NC307)

Hypoplastic left heart syndrome is a congenital cardiovascular malformation in liveborn
human infants that is lethal in untreated form. It is similar to dioxin-induced
hypoplastic heart failure in zebrafish larvae. The incidence of this disorder in human infants
is excessive in certain areas of the U.S.&s_comma; however&s_comma; its etiology is poorly understood. We are
using hypoplastic heart failure in dioxin-exposed zebrafish larvae to gain insight into the
molecular and cellular basis of this birth defect involving the heart. Dioxin developmental
toxicity is manifested in zebrafish larvae by edema&s_comma; anemia&s_comma; hemorrhage and ischemia
associated with arrested growth and development. Heart development and function are
severely impaired. AHR/ARNT signaling pathway that mediates dioxin toxicity has been
characterized in zebrafish larvae and induction of CYP1A by dioxin is not required for toxicity.
Thus&s_comma; the zebrafish larval heart stands out as being highly responsive to dioxin at both the
level of toxicity and gene expression. Ongoing research is aimed at identifying AHR target
genes and signaling pathways required for hypoplastic heart failure&s_comma; findings of interest to
toxicologists&s_comma; pediatric cardiologists and epidemiologists.

Antkiewicz et al.&s_comma; Blocking expression of AHR2 and ARNT1 in zebrafish larvae protects against cardiac
toxicity of 2&s_comma;3&s_comma;7&s_comma;8-tetrachlorodibenzo-p-dioxin. Toxicol Sci 94:175-82&s_comma; 2006.
Carney et al.&s_comma; AHR activation produces heart-specific transcriptional and toxic responses in developing
zebrafish. Molec. Pharmacol. 70: 1-13&s_comma; 2006.
Prasch et al.&s_comma; Identification of zebrafish ARNT1 homologs: 2&s_comma;3&s_comma;7&s_comma;8-Tetrachlorodibenzo-p-dioxin toxicity
in the developing zebrafish requires ARNT1. Mol. Pharmacol. 69: 776-87&s_comma; 2006.


URL http://env-health.m.u-tokyo.ac.jp/seminar0913.pdf

医学系研究科 疾患生命工学センター 健康・環境医工学部門 遠山千春
E-mail: ctohyama@m.u-tokyo.ac.jp
Tel: 03-5841-1917 (内21917)