Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan.
Biometals. 2010 Oct;23(5):941-50. doi: 10.1007/s10534-010-9296-2. Epub 2010 Feb 4.
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.
镉优先积聚在肾脏中，是与镉相关毒性的主要靶器官。有几种潜在的机制被假设，活性氧（ROS）被认为是组织损伤的关键介质。除了氧化应激外，我们最近还揭示内质网（ER）应激也起着关键作用。镉在体外和体内引起 ER 应激，并介导靶组织中细胞凋亡的诱导。在本文中，我们描述了 ER 应激的作用以及未折叠蛋白反应（UPR）的特定分支在镉引发的组织损伤，特别是肾毒性中的作用。我们还讨论了氧化应激和 ER 应激之间的关系，以及选择性 ROS 在诱导 UPR 的促凋亡分支中的作用。
