Glutaredoxin 2 (human, recombinant)

Glutaredoxin 2 (Grx2) is a thiol-disulfide oxidoreductase and member of the thioredoxin family encoded by GLRX2 with a role in the maintenance of cellular thiol redox homeostasis.^1,2 Alternative splicing of GLRX2 produces three ubiquitously expressed isoforms, Grx2a, Grx2b, and Grx2c, with Grx2a localized to the mitochondria and Grx2b and Grx2c in the cytoplasm and nucleus. It is a dithiol Grx that contains two active site cysteine residues and catalyzes the glutathione-dependent reduction of disulfides, acting as an electron donor for ribonucleotide or sulfate reduction, and regulating protein levels of glutathione mixed disulfides.² In its inactive state, Grx2 is a homodimer linked by a single [2Fe-2S] cluster, which acts as a redox sensor that drives monomerization and activation of Grx2 under conditions of oxidative stress, such as free radical formation or oxidation of the glutathione (GSH) pool.^2,3,4 The oxidized active site in Grx2 is reduced by GSH and, unlike other eukaryotic Grxs, is also a substrate for thioredoxin reductase (TrxR). Grx2 catalyzes the reversible glutathionylation of mitochondrial complex I to regulate superoxide production and facilitates the reduction of protein disulfides, glutathionylated proteins, and other low molecular weight substrates under conditions of oxidative stress.⁵ Knockdown or overexpression of GLRX2 enhances and reduces, respectively, oxidative stress-induced apoptosis in HeLa cells. Glrx2 knockdown increases high-fat diet-induced insulin resistance, hippocampal inflammation, increases in body weight, and cognitive dysfunction in mice.⁶ Cayman’s Glutaredoxin 2 (human, recombinant) protein can be used for enzyme activity assays.

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1. Hanschmann, E.-M., Godoy, J.R., Berndt, C., et al. Thioredoxins, glutaredoxins, and peroxiredoxins—molecular mechanisms and health significance: From cofactors to antioxidants to redox signaling. Antioxid. Redox Signal. 19(13), 1539-1605 (2013).

2. Lillig, C.H., Berndt, C., Vergnolle, O., et al. Characterization of human glutaredoxin 2 as iron-sulfur protein: A possible role as redox sensor. Proc. Natl. Acad. Sci. USA 102(23), 8168-8173 (2005).

3. Beer, S.M., Taylor, E.R., Brown, S.E., et al. Glutaredoxin 2 catalyzes the reversible oxidation and glutathionylation of mitochondrial membrane thiol proteins: Implications for mitochondrial redox regulation and antioxidant defense. The Journal of Biological Chemisty 279(46), 47939-47951 (2004).

4. Berndt, C., Hudemann, C., Hanschmann, E.-M., et al. How does iron-sulfur cluster coordination regulate the activity of human glutaredoxin 2? Antioxid. Redox Signal. 9(1), 151-157 (2007).

5. Berndt, C., Lillig, C.H., and Holmgren, A. Thiol-based mechanisms of the thioredoxin and glutaredoxin systems: Implications for diseases in the cardiovascular system. Am. J. Physiol. Heart Circ. Physiol. 292(3), H1227-H1236 (2007).

6. Wohua, Z., and Weiming, X. Glutaredoxin 2 (GRX2) deficiency exacerbates high fat diet (HFD)-induced insulin resistance, inflammation and mitochondrial dysfunction in brain injury: A mechanism involving GSK-3β. Biomed. Pharmacother. 118, 108940 (2019).