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  • Cadmium activates a programmed, lysosomal membrane permeabilization-dependent necrosis pathway.

Cadmium activates a programmed, lysosomal membrane permeabilization-dependent necrosis pathway.

Toxicology letters (2012-06-09)
Barbara Messner, Christian Ploner, Günther Laufer, David Bernhard
ABSTRACT

Cadmium is a highly toxic, carcinogenic, and atherogenic element. A central principle in many Cd-induced pathophysiologies is the induction of cell death. In past studies Cd was shown to cause apoptosis, necrosis, programmed necrosis, or autophagy. This study was conducted to precisely define the end stage processes and outcome of Cd-induced cell death in endothelial cells (ECs). We show that Cd leads to acidification and permeabilization of lysosomes, followed by the release of active DNAse II from lysosomes. The absence of nuclear DNA due to DNAse II activity may have lead to misinterpretations of the type of cell death outcome in previous studies. Further, Cd-induced cell death is characterized by a massive release of lactate dehydrogenase (LDH), a gold standard marker for the occurrence of plasma membrane rupture i.e. necrosis. Importantly, lentivirus-based over-expression of the anti-apoptotic protein BCL-XL abrogates lysosomal rupture, DNA degradation and LDH release, clearly indicating that Cd induces a programmed form of cell death with a necrotic endpoint.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-LC3 antibody produced in rabbit, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Deoxyribonuclease II from bovine spleen, Type V, essentially salt-free, lyophilized powder, ≥1,000 units/mg protein
Sigma-Aldrich
Deoxyribonuclease II from porcine spleen, Type IV, lyophilized powder, 2,000-6,000 Kunitz units/mg protein (biuret)