title: The cadmium-induced death of mesangial cells results in nephrotoxicity.
abstract: This study summarizes our most recent findings on the mechanisms underlying the cadmium-induced death of mesangial cells, which leads to nephrotoxicity. Multiple pathways participate in cadmium-induced nephrotoxicity. In the ROS-GSK-3beta autophagy pathway, cadmium induces ROS most likely from the mitochondria, and the ROS consequently activate GSK-3beta leading to autophagic cell death. In the calcium-ERK autophagy and apoptosis pathway, cadmium stimulates calcium release from the endoplasmic reticulum, which activates ERK leading to predominantly autophagic cell death and a minor level of apoptotic cell death. In the calcium-mitochondria-caspase apoptosis pathway, cadmium-induced elevation of calcium depolarizes the mitochondrial membrane potential and then activates caspase signaling leading to apoptosis. A proposed model for cadmium-induced autophagy and apoptosis leading to nephrotoxicity is summarized in Figure 1.
authors.affiliation: Department of Physiology, College of Medicine and Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan.
authors.forename: Liang-Yo
authors.initials: LY
authors.lastname: Yang
authors.forename: Kuan-Hsun
authors.initials: KH
authors.lastname: Wu
authors.forename: Wen-Ta
authors.initials: WT
authors.lastname: Chiu
authors.forename: Sheng-Hao
authors.initials: SH
authors.lastname: Wang
authors.forename: Chwen-Ming
authors.initials: CM
authors.lastname: Shih