title: Dissipation of mitochondrial membrane potential by exogenous phospholipid monohydroperoxide and protection against this effect by transfection of cells with phospholipid hydroperoxide glutathione peroxidase gene.
abstract: Two hours after its addition to cultures of a guinea pig cell line, 104C1, dilinoleoyl phosphatidylcholine monohydroperoxide (PCOOH) at concentrations of 5-160 microM induced a dissipation of the mitochondrial inner membrane potential (delta psi m), without any apparent morphological changes, in the cells. The PCOOH-induced loss of delta psi m was restored 4 hr after the replacement of the medium with PCOOH-free fresh medium. In contrast, 104C1/O4C cells, a stable clone from 104C1 cells transfected with the human phospholipid hydroperoxide glutathione peroxidase (PHGPx) gene encoding a sequence including a signal peptide towards mitochondria, were resistant to the loss of delta psi m after a 2-hr exposure to PCOOH at concentrations up to 160 microM. Even after an 8-hr exposure to 80 microM PCOOH, the transfected cells retained their delta psi m intact, though the parent cells were killed by the same treatment. The present results strongly suggest that the expression of PHGPx protected the host cells from PCOOH-mediated injury at least by protecting their mitochondria from lipid hydroperoxide-induced loss of delta psi m.
authors.affiliation: Gifu International Institute of Biotechnology, Japan. yagiab@po.infosphere.or.jp
authors.forename: K
authors.initials: K
authors.lastname: Yagi
authors.forename: Y
authors.initials: Y
authors.lastname: Shidoji
authors.forename: S
authors.initials: S
authors.lastname: Komura
authors.forename: H
authors.initials: H
authors.lastname: Kojima
authors.forename: N
authors.initials: N
authors.lastname: Ohishi
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006168:Guinea Pigs; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology; D008054:Lipid Peroxides / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects*; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology; D010713:Phosphatidylcholines / Q000378:metabolism / Q000494:pharmacology; D021382:Protein Sorting Signals / Q000235:genetics; D014162:Transfection / Q000235:genetics
chemical_list: D008054:Lipid Peroxides; D010713:Phosphatidylcholines; D021382:Protein Sorting Signals; C002448:1,2-linoleoylphosphatidylcholine; D005979:Glutathione Peroxidase