Target Genes
Activation of Nrf2 results in the induction of many cytoprotective proteins. These include, but are not limited to, the following:
- NAD(P)H quinone oxidoreductase 1 (Nqo1) is a prototypical Nrf2 target gene that catalyzes the reduction and detoxification of highly reactive quinones that can cause redox cycling and oxidative stress.
- Glutamate-cysteine ligase, catalytic (Gclc) and glutamate-cysteine ligase, modifier (GCLM) subunits form a heterodimer, which is the rate-limiting step in the synthesis of glutathione (GSH), a very powerful endogenous antioxidant. Both Gclc and Gclm are characteristic Nrf2 target genes, which establish Nrf2 as a regulator of glutathione, one of the most important antioxidants in the body.
- Heme oxygenase-1 (HMOX1, HO-1) is an enzyme that catalyzes the breakdown of heme into the antioxidant biliverdin, the anti-inflammatory agent carbon monoxide, and iron. HO-1 is a Nrf2 target gene that has been shown to protect from a variety of pathologies, including sepsis, hypertension, atherosclerosis, acute lung injury, kidney injury, and pain. In a recent study, however, induction of HO-1 has been shown to exacerbate early brain injury after intracerebral hemorrhage.
- The glutathione S-transferase (GST) family includes cytosolic, mitochondrial, and microsomal enzymes that catalyze the conjugation of GSH with endogenous and xenobiotic electrophiles. After detoxification by GSH conjugation catalyzed by GSTs, the body can eliminate potentially harmful and toxic compounds. GSTs are induced by Nrf2 activation and represent an important route of detoxification.
- The UDP-glucuronosyltransferase (UGT) family catalyze the conjugation of a glucuronic acid moiety to a variety of endogenous and exogenous substances, making them more water soluble and readily excreted. Important substrates for glucuronidation include bilirubin and acetaminophen. Nrf2 has been shown to induce UGT1A1 and UGT1A6.
- Multidrug resistance-associated proteins (Mrps) are important membrane transporters that efflux various compounds from various organs and into bile or plasma, with subsequent excretion in the feces or urine, respectively. Mrps have been shown to be upregulated by Nrf2 and alteration in their expression can dramatically alter the pharmacokinetics and toxicity of compounds.
Read more about this topic: NFE2L2
Famous quotes containing the words target and/or genes:
“Well gentlemen, this is it. This is what weve been waiting for. Tonight your target is Tokyo. And youre gonna play em the Star Spangled Banner with two-ton bombs. All youve got to do is to remember what youve learned and follow your squadron leaders. Theyll get you in, and theyll get you out. Any questions? All right thats all. Good luck to you. Give em hell.”
—Dudley Nichols (18951960)
“Whether you want it or not,
your genes have a political past,
your skin a political tone.
your eyes a political color.
...
you walk with political steps
on political ground.”
—Wislawa Szymborska (b. 1923)