Impact of endogenous nitric oxide on microglial cell energy metabolism and labile iron pool.

Benoît Chénais (1) , Hamid Morjani (1) , Jean-Claude Drapier (2)

1 MéDIAN - Médicaments : Dynamique Intracellulaire et Architecture Nucléaire
2 ICSN - Institut de Chimie des Substances Naturelles

Microglial activation is common in several neurodegenerative disorders. In the present study, we used the murine BV-2 microglial cell line stimulated with gamma-interferon and lipopolysaccharide to gain new insights into the effects of endogenously produced NO on mitochondrial respiratory capacity, iron regulatory protein activity, and redox-active iron level. Using polarographic measurement of respiration of both intact and digitonin-permeabilized cells, and spectrophotometric determination of individual respiratory chain complex activity, we showed that in addition to the reversible inhibition of cytochrome-c oxidase, long-term endogenous NO production reduced complex-I and complex-II activities in an irreversible manner. As a consequence, the cellular ATP level was decreased in NO-producing cells, whereas ATPase activity was unaffected. We show that NO up-regulates RNA-binding of iron regulatory protein 1 in microglial cells, and strongly reduces the labile iron pool. Together these results point to a contribution of NO derived from inflammatory microglia to the misregulation of energy-producing reactions and iron metabolism, often associated with the pathogenesis of neurodegenerative disorders.

Domaines: Biochimie, Biologie Moléculaire

Benoît Chénais, Hamid Morjani, Jean-Claude Drapier. Impact of endogenous nitric oxide on microglial cell energy metabolism and labile iron pool.. Journal of Neurochemistry, 2002, 81 (3), pp.615-23. ⟨hal-00422911⟩