Glutathione regulates susceptibility to oxidant-induced mitochondrial DNA damage in human lymphocytes.

Published

Journal Article

Oxidative damage to mitochondrial DNA (mtDNA) interferes with the expression of mitochondrial-encoded subunits of the electron transport complexes of oxidative phosphorylation. MtDNA is protected by several mitochondrial antioxidant systems, but the specific importance of glutathione is unknown. We hypothesized that glutathione protects mtDNA from oxidative damage in human blood lymphocytes and that glutathione depletion increases susceptibility to mtDNA depletion, which increases vulnerability to apoptosis. MtDNA damage was measured in human blood lymphocytes exposed to tert-butyl-hydroperoxide (t-BOOH) or t-BOOH plus the glutathione analog, glutathione ethyl ester (GEE). Mitochondrial oxidative stress, mtDNA damage, and susceptibility to apoptosis were analyzed after glutathione depletion with buthionine sulfoximine (BSO). The data show selective damage to lymphocyte mtDNA at low concentrations of tBOOH that is attenuated by glutathione supplementation. Moreover, inhibition of glutathione synthesis led to lymphocyte ROS generation and mtDNA damage, and increased susceptibility to receptor-mediated apoptosis. These findings implicate the glutathione system in maintaining mtDNA integrity and resistance to apoptosis in lymphocytes and suggest that assessment of mtDNA damage in blood lymphocytes may be a useful marker of oxidative stress in humans.

Full Text

Duke Authors

Cited Authors

  • Hollins, DL; Suliman, HB; Piantadosi, CA; Carraway, MS

Published Date

  • April 1, 2006

Published In

Volume / Issue

  • 40 / 7

Start / End Page

  • 1220 - 1226

PubMed ID

  • 16545690

Pubmed Central ID

  • 16545690

International Standard Serial Number (ISSN)

  • 0891-5849

Digital Object Identifier (DOI)

  • 10.1016/j.freeradbiomed.2005.11.011

Language

  • eng

Conference Location

  • United States