Human glutamate cysteine ligase gene regulation through the electrophile response element
Free Radical Biology and Medicine, 2004•Elsevier
Glutathione (GSH) is the primary nonprotein thiol in the cell. It has many important roles in
cell function, including regulating redox-dependent signal transduction pathways. The
content of GSH within the cell varies with stress. In many cases, a process involving GSH
synthesis results in adaptation to subsequent stressors. Sustained increases in GSH content
are controlled primarily through induction of two genes, Gclc and Gclm, leading to the
synthesis of the rate-limiting enzyme for GSH synthesis, glutamate cysteine ligase. Each of …
cell function, including regulating redox-dependent signal transduction pathways. The
content of GSH within the cell varies with stress. In many cases, a process involving GSH
synthesis results in adaptation to subsequent stressors. Sustained increases in GSH content
are controlled primarily through induction of two genes, Gclc and Gclm, leading to the
synthesis of the rate-limiting enzyme for GSH synthesis, glutamate cysteine ligase. Each of …
Glutathione (GSH) is the primary nonprotein thiol in the cell. It has many important roles in cell function, including regulating redox-dependent signal transduction pathways. The content of GSH within the cell varies with stress. In many cases, a process involving GSH synthesis results in adaptation to subsequent stressors. Sustained increases in GSH content are controlled primarily through induction of two genes, Gclc and Gclm, leading to the synthesis of the rate-limiting enzyme for GSH synthesis, glutamate cysteine ligase. Each of these genes in humans has a number of putative enhancer elements in their promoters. Overall, the most important element in both Gclc and Gclm expression is the electrophile response element. We review the evidence that has led to this conclusion and the implications for the redox-dependent regulation of this critical intracellular antioxidant.
Elsevier