Effects of diverse intracellular thiol delivery agents on glutathione peroxidase activity, the ratio of reduced/oxidized glutathione, and ornithine decarboxylase induction in isolated mouse epidermal cells treated with 12-O-tetradecanoylphorbol-13-acetate

J Cell Physiol. 1987 Apr;131(1):64-73. doi: 10.1002/jcp.1041310111.

Abstract

Since the enhancement of the activity of the natural glutathione (GSH)-dependent antioxidant protective system of the epidermal cells appears to inhibit the oxidative challenge presumably linked to skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA), we have compared the effectiveness of diverse intracellular thiol delivery agents as inhibitors of the effects of TPA on GSH metabolism and ornithine decarboxylase (ODC; L-ornithine carboxylase, EC 4.1.1.17) induction in isolated mouse epidermal cells. Here we report at a 2-mM concentration, the monoethyl and monomethyl esters of GSH, N-acetyl-L-cysteine, and L-2-oxothiazolidine-4-carboxylate are all significantly more effective than GSH in inhibiting the sharp decline in the intracellular ratio of reduced GSH/oxidized glutathione (GSSG), the prolonged decrease in GSH peroxidase (GSH:H2O2 oxidoreductase, EC 1.11.1.9) activity, and the induction of ODC activity caused by 1 microM TPA. Moreover, diethyldithiocarbamate prevents totally the initial drop in the GSH/GSSG ratio of TPA-treated cells and is the most potent inhibitor of TPA-decreased GSH peroxidase activity in relation with its remarkable 98% inhibition of TPA-induced ODC activity, suggesting that the potential antitumor-promoting activity of this compound in mouse skin may be far superior to that previously demonstrated by GSH in the initiation-promotion protocol.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcysteine / pharmacology
  • Animals
  • Cells, Cultured
  • Ditiocarb / pharmacology
  • Epidermis / drug effects
  • Epidermis / enzymology*
  • Female
  • Glutathione / analogs & derivatives
  • Glutathione / metabolism*
  • Glutathione / pharmacology
  • Glutathione Peroxidase / metabolism*
  • Mice
  • Mice, Inbred Strains
  • Ornithine Decarboxylase / metabolism*
  • Oxidation-Reduction
  • Pyrrolidonecarboxylic Acid
  • Sulfhydryl Compounds / pharmacology*
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Thiazoles / pharmacology
  • Thiazolidines

Substances

  • Sulfhydryl Compounds
  • Thiazoles
  • Thiazolidines
  • S-ethyl glutathione
  • Ditiocarb
  • Glutathione Peroxidase
  • Ornithine Decarboxylase
  • Glutathione
  • Tetradecanoylphorbol Acetate
  • S-methyl glutathione
  • Pyrrolidonecarboxylic Acid
  • Acetylcysteine
  • 2-oxothiazolidine-4-carboxylic acid