The oxidative stress: endoplasmic reticulum stress axis in cadmium toxicity.
Cadmium preferentially accumulates in the kidney, the major target for cadmium-related toxicity. Several underlying mechanisms are postulated, and reactive oxygen species (ROS) have been considered as crucial mediators for tissue injuries. In addition to oxidative stress, we recently disclosed that endoplasmic reticulum (ER) stress also plays a critical role. Cadmium causes ER stress in vitro and in vivo and mediates induction of apoptosis in target tissues. In this article, we describe a role for ER stress and involvement of particular branches of the unfolded protein response (UPR) in cadmium-triggered tissue injury, especially nephrotoxicity. We also discuss relationship between oxidative stress and ER stress, and involvement of selective ROS in the induction of pro-apoptotic branches of the UPR.
Kitamura
Masanori
M
Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan. masanori@yamanashi.ac.jp
Hiramatsu
Nobuhiko
N
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002104:Cadmium / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism*; D004785:Environmental Pollutants / Q000633:toxicity; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D056811:Unfolded Protein Response / Q000187:drug effects
D004785:Environmental Pollutants; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D002104:Cadmium; D013481:Superoxides