Skip to Main content Skip to Navigation
Journal articles

Regulation of apoptosis/necrosis execution in cadmium-treated human promonocytic cells under different forms of oxidative stress.

Abstract : Pulse-treatment of U-937 human promonocytic cells with cadmium chloride followed by recovery caused caspase-9/caspase-3-dependent, caspase-8-independent apoptosis. However, pre-incubation with the glutathione (GSH)-suppressing agent DL-buthionine-(S,R)-sulfoximine (cadmium/BSO), or co-treatment with H2O2 (cadmium/H2O2), switched the mode of death to caspase-independent necrosis. The switch from apoptosis to necrosis did not involve gross alterations in Apaf-1 and pro-caspase-9 expression, nor inhibition of cytochrome c release from mitochondria. However, cadmium/H2O2-induced necrosis involved ATP depletion and was prevented by 3-aminobenzamide, while cadmium/BSO-induced necrosis was ATP independent. Pre-incubation with BSO increased the intracellular cadmium accumulation, while co-treatment with H2O2 did not. Both treatments caused intracellular peroxide over-accumulation and disruption of mitochondrial transmembrane potential (delta psi m). However, while post-treatment with N-acetyl-L-cysteine or butylated hydroxyanisole reduced the cadmium/BSO-mediated necrosis and delta psi m disruption, it did not reduce the effects of cadmium/H2O2. Bcl-2 over-expression, which reduced peroxide accumulation without affecting the intracellular GSH content, attenuated necrosis generation by cadmium/H2O2 but not by cadmium/BSO. By contrast, AIF suppression, which reduced peroxide accumulation and increased the GSH content, attenuated the toxicity of both treatments. These results unravel the existence of two different oxidation-mediated necrotic pathways in cadmium-treated cells, one of them resulting from ATP-dependent apoptosis blockade, and the other involving the concurrence of multiple regulatory factors.
Document type :
Journal articles
Complete list of metadatas

https://hal-pasteur.archives-ouvertes.fr/pasteur-00165714
Contributor : Marie-Dominique Aytac <>
Submitted on : Friday, July 27, 2007 - 12:04:58 PM
Last modification on : Monday, January 13, 2020 - 5:08:10 PM

Links full text

Identifiers

Collections

Citation

P. Sancho, C. Fernández, V. J. Yuste, D. Amrán, A. M. Ramos, et al.. Regulation of apoptosis/necrosis execution in cadmium-treated human promonocytic cells under different forms of oxidative stress.. Apoptosis, Springer Verlag, 2006, 11 (5), pp.673-86. ⟨10.1007/s10495-006-5879-3⟩. ⟨pasteur-00165714⟩

Share

Metrics

Record views

182