title: Oxidized redox state of glutathione in the endoplasmic reticulum.
abstract: The redox state of the endoplasmic reticulum (ER) was measured with the peptide N-Acetyl-Asn-Tyr-Thr-Cys-NH2. The peptide diffused across cellular membranes; some became glycosylated and thus trapped within the secretory pathway, and its cysteine residue underwent reversible thiol-disulfide exchanges with the surrounding redox buffer. Glycosylated peptides from cells were disulfide-linked to glutathione, indicating that glutathione is the major redox buffer in the secretory pathway. The redox state of the secretory pathway was more oxidative than that of the cytosol; the ratio of reduced glutathione to the disulfide form (GSH/GSSG) within the secretory pathway ranged from 1:1 to 3:1, whereas the overall cellular GSH/GSSG ratio ranged from 30:1 to 100:1. Cytosolic glutathione was also transported into the lumen of microsomes in a cell-free system. Although how the ER maintains an oxidative environment is not known, these results suggest that the demonstrated preferential transport of GSSG compared to GSH into the ER lumen may contribute to this redox compartmentation.
authors.affiliation: Department of Biology, Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142.
authors.forename: C
authors.initials: C
authors.lastname: Hwang
authors.forename: A J
authors.initials: AJ
authors.lastname: Sinskey
authors.forename: H F
authors.initials: HF
authors.lastname: Lodish
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004285:Dogs; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism*; D019803:Glutathione Disulfide; D007700:Kinetics; D008861:Microsomes / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000302:isolation & purification / Q000378:metabolism*; D010084:Oxidation-Reduction; D010179:Pancreas / Q000378:metabolism
chemical_list: D009842:Oligopeptides; D005978:Glutathione; D019803:Glutathione Disulfide