Inactivation of mitochondrial NADP+-dependent isocitrate dehydrogenase by hypochlorous acid.

Abstract:

:Myeoloperoxidase catalyses the formation of hypochlorous acid (HOCl) via reaction of H(2)O(2) with Cl(-) ion. Although HOCl is known to play a major role in the human immune system by killing bacteria and other invading pathogens, excessive generation of this oxidant is known to cause damage to tissue. Recently, it was demonstrated that the control of mitochondrial redox balance and oxidative damage is one of the primary functions of mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm) to supply NADPH for antioxidant systems. This study investigated whether the IDPm would be a vulnerable target of HOCl as a purified enzyme and in intact cells. Loss of enzyme activity was observed and the inactivation of IDPm was reversed by thiols. Transfection of HeLa cells with an IDPm small interfering RNA (siRNA) markedly enhanced HOCl-induced oxidative damage to cells. The HOCl-mediated damage to IDPm may result in the perturbation of the cellular antioxidant defense mechanisms and subsequently lead to a pro-oxidant condition.

journal_name

Free Radic Res

journal_title

Free radical research

authors

Park SY,Lee SM,Shin SW,Park JW

doi

10.1080/10715760802098834

subject

Has Abstract

pub_date

2008-05-01 00:00:00

pages

467-73

issue

5

eissn

1071-5762

issn

1029-2470

pii

793185422

journal_volume

42

pub_type

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