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Cadmium and cellular signaling cascades: interactions between cell death and survival pathways.

Archives of toxicology (2013-08-29)
Frank Thévenod, Wing-Kee Lee
ABSTRACT

Cellular stress elicited by the toxic metal Cd(2+) does not coerce the cell into committing to die from the onset. Rather, detoxification and adaptive processes are triggered concurrently, allowing survival until normal function is restored. With high Cd(2+), death pathways predominate. However, if sublethal stress levels affect cells for prolonged periods, as in chronic low Cd(2+) exposure, adaptive and survival mechanisms may deregulate, such that tumorigenesis ensues. Hence, death and malignancy are the two ends of a continuum of cellular responses to Cd(2+), determined by magnitude and duration of Cd(2+) stress. Signaling cascades are the key factors affecting cellular reactions to Cd(2+). This review critically surveys recent literature to outline major features of death and survival signaling pathways as well as their activation, interactions and cross talk in cells exposed to Cd(2+). Under physiological conditions, receptor activation generates 2nd messengers, which are short-lived and act specifically on effectors through their spatial and temporal dynamics to transiently alter effector activity. Cd(2+) recruits physiological 2nd messenger systems, in particular Ca(2+) and reactive oxygen species (ROS), which control key Ca(2+)- and redox-sensitive molecular switches dictating cell function and fate. Severe ROS/Ca(2+) signals activate cell death effectors (ceramides, ASK1-JNK/p38, calpains, caspases) and/or cause irreversible damage to vital organelles, such as mitochondria and endoplasmic reticulum (ER), whereas low localized ROS/Ca(2+) levels act as 2nd messengers promoting cellular adaptation and survival through signal transduction (ERK1/2, PI3K/Akt-PKB) and transcriptional regulators (Ref1-Nrf2, NF-κB, Wnt, AP-1, bestrophin-3). Other cellular proteins and processes targeted by ROS/Ca(2+) (metallothioneins, Bcl-2 proteins, ubiquitin-proteasome system, ER stress-associated unfolded protein response, autophagy, cell cycle) can evoke death or survival. Hence, temporary or permanent disruptions of ROS/Ca(2+) induced by Cd(2+) play a crucial role in eliciting, modulating and linking downstream cell death and adaptive and survival signaling cascades.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Cadmium, powder, −100 mesh, 99.5% trace metals basis
Sigma-Aldrich
Cadmium, granular, 30-80 mesh, ≥99%
Sigma-Aldrich
Cadmium, granular, ≥99%, 5-20 mesh
Cadmium, foil, 100x100mm, thickness 1.0mm, as rolled, 99.99%
Cadmium, wire reel, 0.1m, diameter 0.70mm, as drawn, 99.99+%
Cadmium, wire reel, 0.1m, diameter 1.2mm, as drawn, 99.99+%
Cadmium, wire reel, 0.1m, diameter 2.0mm, hard, 99.99+%
Cadmium, wire reel, 0.1m, diameter 1.0mm, hard, 99.999%
Cadmium, wire reel, 0.2m, diameter 0.25mm, hard, 99.99+%
Cadmium, wire reel, 0.2m, diameter 0.5mm, hard, 99.95+%
Cadmium, wire reel, 0.2m, diameter 0.5mm, hard, 99.99+%
Cadmium, wire reel, 0.2m, diameter 0.70mm, as drawn, 99.99+%
Cadmium, wire reel, 0.2m, diameter 1.2mm, as drawn, 99.99+%
Cadmium, wire reel, 0.2m, diameter 2.0mm, hard, 99.99+%
Cadmium, wire reel, 0.2m, diameter 0.125mm, as drawn, 99.9%
Cadmium, wire reel, 0.2m, diameter 1.0mm, hard, 99.999%
Cadmium, wire reel, 0.5m, diameter 0.25mm, hard, 99.99+%
Cadmium, wire reel, 0.5m, diameter 0.5mm, hard, 99.95+%
Cadmium, wire reel, 0.5m, diameter 0.5mm, hard, 99.99+%
Cadmium, wire reel, 0.5m, diameter 0.70mm, as drawn, 99.99+%
Cadmium, wire reel, 0.5m, diameter 1.2mm, as drawn, 99.99+%
Cadmium, wire reel, 0.5m, diameter 2.0mm, hard, 99.99+%
Cadmium, wire reel, 0.5m, diameter 0.125mm, as drawn, 99.9%
Cadmium, wire reel, 0.5m, diameter 1.0mm, hard, 99.999%
Cadmium, wire reel, 10m, diameter 0.25mm, hard, 99.99+%
Cadmium, wire reel, 1m, diameter 0.25mm, hard, 99.99+%
Cadmium, foil, 100x100mm, thickness 0.125mm, as rolled, 99.95%
Cadmium, foil, 100x100mm, thickness 0.125mm, as rolled, 99.99+%
Cadmium, foil, 100x100mm, thickness 0.25mm, as rolled, 99.99+%
Cadmium, foil, 100x100mm, thickness 2.0mm, as rolled, 99.99%