15-Lipoxygenase-2 (human, recombinant)

Two types of 15-lipoxygenase (15-LO) have been discovered and characterized, both of which metabolize arachidonic acid (AA) to produce 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE). 15-LO-1 oxygenates AA at both C-15 and C-12, whereas 15-LO-2 exclusively oxygenates C-15 of AA.^1,2 Human 15-LO-2 has a molecular mass of approximately 76 kDa and exhibits approximately 40% identity to the reticulocyte 15-LO-1.^2,3 Expression of 15-LO-2 appears to be restricted to prostate, lung, skin, and cornea and may play a role in the normal development of these tissues.⁴ The protein levels and enzymatic activity of 15-LO-2 are both down-regulated in prostate cancer compared with normal and benign prostate tissues, implicating a possible protective role for 15-LO-2 against tumor formation.^4,5,6 Cayman's 15-LO-2 (human, recombinant) is expressed and purified from E. coli. The purity was determined using gel electrophoresis followed by coomassie staining. 15-LO-2 specific activity was established using arachidonic acid as the substrate and monitoring diene formation by measuring absorbance 236 nm.

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1. Kuhn, H., Barnett, J., Grunberger, D., et al. Overexpression, purification and characterization of human recombinant 15-lipoxygenase. Biochim. Biophys. Acta 1169(1), 80-89 (1993).

2. Brash, A.R., Chang, M.S., and Boeglin, W.E. Discovery of a second 15S-lipoxygenase in humans. Proc. Natl. Acad. Sci. USA 94(12), 6148-6152 (1997).

3. Kilty, I., Logan, A., and Vickers, P.J. Differential characteristics of human 15-lipoxygenase isozymes and novel splice variant of 15S-lipoxygenase. Eur. J. Biochem. 266(1), 83-93 (1999).

4. Tang, S., Bhatia, B., Maldonado, C.J., et al. Evidence that arachidonate 15-lipoxygenase 2 is a negative cell cycle regulator in normal prostate epithelial cells. The Journal of Biological Chemisty 277(18), 16189-16201 (2002).

5. Shappell, S.B., Boeglin, W.E., Olson, S.J., et al. 15-lipoxygenase-2 (15-LOX-2) is expressed in benign prostatic epithelium and reduced in prostate adenocarcinoma. Am. J. Pathol. 155(1), 235-245 (1999).

6. Jack, G.S., Brash, A.R., Olson, S.J., et al. Reduced 15-lipoxygenase-2 immunostaining in prostate adenocarcinoma: Correlation with grade and expression in high-grade prostatic intraepithelial neoplasia. Hum. Pathol. 31(9), 1146-1154 (2000).

Anthonymuthu, T.S., Kenny, E.M., Shrivastava, I., et al. Empowerment of 15-lipoxygenase catalytic competence in selective oxidation of membrane ETE-PE to ferroptotic death signals, HpETE-PE. J. Am. Chem. Soc. 140(51), 17835-17839 (2018).

Kagan, V.E., Mao, G., Qu, F., et al. Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis. Nat. Chem. Biol. 13(1), 81-90 (2017).