Regulation of gamma-glutamylcysteine synthetase expression in response to oxidative stress.
Glutathione (GSH) is synthesized by the activity of two ATP-requiring GSH synthesizing enzymes. Gamma-glutamylcysteine synthetase (gamma-GCS) is the rate limiting enzyme for the GSH synthesis. Gamma-GCS is a heterodimer of heavy, catalytic subunit and light, regulatory subunit and responsive to many stresses, such as heat shock, oxidative stress or cytokines. To know the regulation of the expression of gamma-GCS gene, in the present study, we show evidences that gamma-GCS heavy subunit is upregulated by oxidative stress by ionizing radiation and TNF-alpha mediated by nuclear factor-kappaB (NF-kappaB), and impairment of the expression of gamma-GCS by TNF-alpha in diabetic condition. Furthermore we describe the importance of GSH in the regulation of NF-kappaB subunits.
Kondo
T
T
Department of Biochemistry and Molecular Biology in Disease, Nagasaki University School of Medicine, Japan.
Higashiyama
Y
Y
Goto
S
S
Iida
T
T
Cho
S
S
Iwanaga
M
M
Mori
K
K
Tani
M
M
Urata
Y
Y
D000818:Animals; D015971:Gene Expression Regulation, Enzymologic; D005721:Glutamate-Cysteine Ligase / Q000096:biosynthesis*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D005721:Glutamate-Cysteine Ligase