GLUTATHIONE PROTECTS ASTROCYTES FROM PEROXYNITRITE-MEDIATED MITOCHONDRIAL DAMAGE - IMPLICATIONS FOR NEURONAL ASTROCYTIC TRAFFICKING AND NEURODEGENERATION

In this study we have examined the susceptibility of the mitochondrial respiratory chain of astrocytes and astrocytes depleted of glutathion e to peroxynitrite exposure, Astrocytes, as reported previously by us, appeared resistant to the actions of peroxynitrite. In contrast, depl etion (-94%) of astrocytic glutathione rendered the cells susceptible with mitochondrial complexes I and II/III being decreased in activity by 80 and 64%, respectively, after peroxynitrite exposure. Furthermore , cell death, as judged by lactate dehydrogenase release, was signific antly increased (+81%) in the glutathione-depleted astrocytes exposed to peroxynitrite. Glutathione depletion alone had no effect on any of the measured parameters. It is concluded that glutathione is an import ant intracellular defence against peroxynitrite and that when glutathi one levels are compromised the mitochondrial respiratory chain is a vu lnerable target and cell death ensues, In view of the relative paucity of neuronal glutathione, it is possible that astrocyte-derived peroxy nitrite may, in certain pathological conditions, be released and diffu se into neighboring neurones where mitochondrial damage may occur.