Nitric oxide protects the mitochondria of anterior pituitary cells and prevents cadmium-induced cell death by reducing oxidative stress

Cadmium (Cd 2+) is a highly toxic metal that affects the endocrine system. We have previously shown that Cd 2+ induces caspase-3 activation and apoptosis of anterior pituitary cells and that endogenous nitric oxide (NO) protects these cells from Cd 2+. Here we investigate the mechanisms by which NO...

Full description

Saved in:
Bibliographic Details
Published in:Free radical biology & medicine 2006-02, Vol.40 (4), p.679-688
Main Authors: Poliandri, Ariel H.B., Machiavelli, Leticia I., Quinteros, Alnilan F., Cabilla, Jimena P., Duvilanski, Beatriz H.
Format: Article
Language:English
Subjects:
Animals
Anterior pituitary
Apoptosis - drug effects
Cadmium
Cadmium - toxicity
Cells, Cultured
Cyclosporine - pharmacology
Endocrine disruptors
Flow Cytometry
Free radicals
Immunosuppressive Agents - pharmacology
Male
Membrane Potentials - drug effects
Mitochondria
Mitochondria - drug effects
Mitochondrial membrane potential
Nitric oxide
Nitric Oxide - pharmacology
Oxidative stress
Oxidative Stress - drug effects
Pituitary Gland, Anterior - cytology
Pituitary Gland, Anterior - drug effects
Rats
Rats, Wistar
Reactive Oxygen Species - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Cadmium (Cd 2+) is a highly toxic metal that affects the endocrine system. We have previously shown that Cd 2+ induces caspase-3 activation and apoptosis of anterior pituitary cells and that endogenous nitric oxide (NO) protects these cells from Cd 2+. Here we investigate the mechanisms by which NO exerts this protective role. Cd 2+ (25 μM) reduced the mitochondrial membrane potential (MMP) as measured by flow cytometry. Cd 2+-induced apoptosis was mitochondrial dependent since cyclosporin A protected the cells from this metal. Inhibition of NO synthesis with 0.5 mM l-NAME increased the effect of Cd 2+ on MMP, whereas the NO donor DETANONOate (0.1 mM) reduced it. Cd 2+ increased the production of reactive oxygen species (ROS) as measured by flow cytometry. This effect was electron-transfer-chain-dependent since it was inhibited by rotenone. In fact, rotenone reduced the cytotoxic effect of the metal. The action of Cd 2+ on mitochondrial integrity was ROS dependent. Trolox, an antioxidant, inhibited the effect of the metal on the MMP. Cd 2+-induced increase in ROS generation was reduced by DETANONOate. There are discrepancies concerning the role of NO in Cd 2+ toxicity. Here we show that NO reduces Cd 2+ toxicity by protecting the mitochondria from oxidative stress in a system where NO plays a regulatory role.
ISSN:0891-5849
1873-4596
DOI:10.1016/j.freeradbiomed.2005.09.021