Abstract
We investigated whether endogenously or exogenously produced nitric oxide (NO) can inhibit cellular glutathione reductase (GR) via the formation of S-nitrosothiols to decrease cellular glutathione (GSH) and increase oxidative stress in RAW 264.7 cells. The specificity of this inhibition was demonstrated by addition of a NO-synthase inhibitor, and met- or oxyhemoglobin. Using isolated GR we found that only certain NO donors inhibit this enzyme via S-nitrosothiol. Furthermore, we found that cellular GSH decrease is paralleled by an increase of superoxide anion production. Our results show that the GR enzyme is a potential target of S-nitrosothiols to decrease cellular GSH levels and to induce oxidative stress in macrophages.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Cell Line
-
Cysteine / analogs & derivatives
-
Cysteine / metabolism
-
Cysteine / pharmacology
-
Glutathione / analogs & derivatives
-
Glutathione / metabolism
-
Glutathione / pharmacology
-
Glutathione Reductase / metabolism*
-
Macrophages / cytology
-
Macrophages / drug effects
-
Macrophages / metabolism*
-
Mercaptoethanol*
-
Mice
-
Nitric Oxide / metabolism
-
Nitroso Compounds / metabolism*
-
Nitroso Compounds / pharmacology
-
Oxidative Stress / physiology*
-
Reactive Oxygen Species / metabolism
-
S-Nitrosoglutathione
-
S-Nitrosothiols*
-
Superoxides / metabolism
Substances
-
Nitroso Compounds
-
Reactive Oxygen Species
-
S-Nitrosothiols
-
Superoxides
-
Nitric Oxide
-
S-Nitrosoglutathione
-
Mercaptoethanol
-
S-nitrosomercaptoethanol
-
S-nitrosocysteine
-
Glutathione Reductase
-
Glutathione
-
Cysteine