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

Abstract:

: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.

journal_name

J Neurochem

authors

Chénais B,Morjani H,Drapier JC

doi

10.1046/j.1471-4159.2002.00864.x

keywords:

subject

Has Abstract

pub_date

2002-05-01 00:00:00

pages

615-23

issue

3

eissn

0022-3042

issn

1471-4159

journal_volume

81

pub_type

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