DSpace university logo mark
Japanese | English 

NAOSITE : Nagasaki University's Academic Output SITE > 030 医学部 > 030 紀要 > Acta Medica Nagasakiensia > Volume 50, No. supl.1 >

A Paradigm Shift in the Understanding of Oxidative Stress and its Implications to Exposure of Low-level Ionizing Radiation

ファイル 記述 サイズフォーマット
acta50_s1_63.pdf792.33 kBAdobe PDF本文ファイル

タイトル: A Paradigm Shift in the Understanding of Oxidative Stress and its Implications to Exposure of Low-level Ionizing Radiation
著者: L..Upham, Brad / E..Trosko, James
発行日: 2005年12月
引用: Acta medica Nagasakiensia. 2005, 50(supl.1), p.63-68
抄録: For many years, research on oxidative stress focused primarily on determining how reactive oxygen species (ROS) damage cells by indiscriminate reactions with its macromolecular machinery, particularly lipids, proteins and DNA. However, many chronic diseases affiliated with oxidative stress are not always a consequence of tissue necrosis, DNA, or protein damage but rather to altered gene expression. Gene expression is highly regulated by the coordination of extra-, intra- and inter-cellular communication systems that typically maintain tissue homeostasis by sustaining a balance between proliferation, differentiation and apoptosis. Therefore, much research has shifted to the understanding of how ROS reversibly controls gene expression at noncytotoxic doses through cell signaling mechanisms. Cell proliferation typically involves a transient inhibition of gap junctional intercellular communication (GJIC) and the activation of mitogen activated protein kinase pathways (MAPK). We demonstrate that epidermal growth factor (EGF) inhibited GJIC in normal rat liver epithelial cells in addition to activating extracellular signal regulatory kinase, a MAPK. Inhibition of NADPH oxidase, which reduces oxygen to H2O2 with the very selective inhibitor diphenyleneiodonium, prevented EGF from inhibiting GJIC, suggesting that the generation of H2O2 is an essential component of the intracellular pathway controlling GJIC. We previously demonstrated that reduced-glutathione (GSH) was also a necessary cofactor of H2O2-induced inhibition of GJIC. These results demonstrate that ROS and GSH play essential roles in controlling EGF-dependent control of GJIC. Therefore, the overly simplistic approach of either preventing the generation of ROS or accelerate the removal by antioxidants could deleteriously alter normal signaling functions.
キーワード: Oxidativestress / Gapjunctionalintercellularcommunication / Epigenetictoxicity / Cancer / NADPHoxidase / Signaltransduction
URI: http://hdl.handle.net/10069/9314
ISSN: 00016055
関連リンク : http://joi.jlc.jst.go.jp/JST.JSTAGE/amn/50.S63
資料タイプ: Departmental Bulletin Paper
原稿種類: publisher
出現コレクション:Volume 50, No. supl.1

引用URI : http://hdl.handle.net/10069/9314



Valid XHTML 1.0! Copyright © 2006-2015 長崎大学附属図書館 - お問い合わせ Powerd by DSpace