Protective effects of the glutathione redox cycle and vitamin E on cultured
fibroblasts infected by Mycoplasma pneumoniae.
Infect Immun 1986 Apr;52(1):240-4 (ISSN: 0019-9567)
Almagor M; Kahane I; Gilon C; Yatziv S
The role of the glutathione (GSH) redox cycle and vitamin E as antioxidant
defense systems was studied in normal human cultured skin fibroblasts
infected by virulent Mycoplasma pneumoniae. In cells infected for 20 h,
catalase activity was inhibited by 75% and the intracellular GSH decreased
to 32% of its normal values. GSH peroxidase and oxidized glutathione (reductase
activities in the infected cells were unaffected.) GSSG glutathione in
the medium of the infected cells rose in accordance with the intracellular
GSH decrease. The observed elevation in GSSG/GSH ratio was attributed
to the increase in intracellular H2O2 content in M. pneumoniae-infected
cells due to the marked inhibition in their catalase activity. The protective
effect of the GSH redox cycle in infected cells was studied by depletion
of cellular GSH, prior to their infection with M. pneumoniae, using buthionine
sulfoximine (BSO), a selective inhibitor of gamma-glutamyl cysteine synthetase.
After 16 h of incubation with BSO, the GSH levels were reduced to 38%
of their normal value and recovered to 55% during 24 h after removal of
the inhibitor. BSO had no effect on GSH peroxidase and catalase activities
in either infected or noninfected cells. The level of malonyldialdehyde
(an indicator of membrane lipid peroxidation) in BSO-treated cells infected
by M. pneumoniae was 1.8 times higher than in infected controls. Cells
enriched with 0.25 and 2.25 micrograms of vitamin E per mg of protein
prior to their infection by M. pneumoniae revealed the following: a lesser
degree of catalase inhibition, 46 and 30%, respectively, versus 64% in
infected control cells that were not supplemented with vitamin E; lower
levels of malonyldialdehyde, 55 and 20% increments, respectively, versus
a 140% increment in infected controls; higher residual activity of lactate
dehydrogenase, 76 and 96%, respectively, versus 58% in infected controls.
Our data indicate that the oxidative damage induced in M. pneumoniae-infected
cells due to the increase in intracellular levels of H2O2 and O2- is limited
by the host cell GSH redox cycle and by supplementation with vitamin E.