Cis-Urocanic acid explained

cis-Urocanic acid (cis-UCA) is a chemical compound produced by ultraviolet irradiation of trans-urocanic acid, a metabolite naturally formed in the body from histidine. cis-Urocanic acid is suspected of involvement in the development of skin cancer. It acts as an immunosuppressant through action as an agonist of the 5-HT_2A receptor, and blocking this receptor has been shown to reduce cis-UCA mediated photocarcinogenesis.^{[1] [2] [3]} However the immunomodulatory effects of cis-UCA are complex and also involve other pathways, and at low levels it shows antiinflammatory actions and may be protective against UV damage in the cornea and retina.^{[4] [5] [6] [7] [8] [9]}

Notes and References

1. Walterscheid JP, Nghiem DX, Kazimi N, Nutt LK, McConkey DJ, Norval M, Ullrich SE . Cis-urocanic acid, a sunlight-induced immunosuppressive factor, activates immune suppression via the 5-HT2A receptor . Proceedings of the National Academy of Sciences of the United States of America . 103 . 46 . 17420–17425 . November 2006 . 10.1073/pnas.0603119103 . free . 17085585 . 1859944 .
2. Shen L, Ji HF . Molecular basis for cis-urocanic acid as a 5-HT(2A) receptor agonist . Bioorganic & Medicinal Chemistry Letters . 19 . 18 . 5307–5309 . September 2009 . 10.1016/j.bmcl.2009.07.143 . 19683920 .
3. Menezes AC, Raposo S, Simões S, Ribeiro H, Oliveira H, Ascenso A . Prevention of Photocarcinogenesis by Agonists of 5-HT1A and Antagonists of 5-HT2A Receptors . Molecular Neurobiology . 53 . 2 . 1145–1164 . March 2016 . 10.1007/s12035-014-9068-z . 25589005 . 14282500 .
4. Norval M, El-Ghorr AA . Studies to determine the immunomodulating effects of cis-urocanic acid . Methods . 28 . 1 . 63–70 . September 2002 . 10.1016/s1046-2023(02)00210-4 . 12231189 .
5. Schwarz T . Mechanisms of UV-induced immunosuppression . The Keio Journal of Medicine . 54 . 4 . 165–71 . December 2005 . 16452825 . 10.2302/kjm.54.165. free .
6. Ullrich SE . Sunlight and skin cancer: lessons from the immune system . Molecular Carcinogenesis . 46 . 8 . 629–633 . August 2007 . 10.1002/mc.20328 . 17443748 . 2661262 .
7. Lucas RM, Byrne SN, Correale J, Ilschner S, Hart PH . Ultraviolet radiation, vitamin D and multiple sclerosis . Neurodegenerative Disease Management . 5 . 5 . 413–424 . October 2015 . 10.2217/nmt.15.33 . 26477548 .
8. Korhonen E, Bisevac J, Hyttinen JM, Piippo N, Hytti M, Kaarniranta K, Petrovski G, Kauppinen A . 6 . UV-B-Induced Inflammasome Activation Can Be Prevented by Cis-Urocanic Acid in Human Corneal Epithelial Cells . Investigative Ophthalmology & Visual Science . 61 . 4 . 7 . April 2020 . 10.1167/iovs.61.4.7 . 32271889 . 7401861 .
9. Korhonen E, Piippo N, Hytti M, Kaarniranta K, Kauppinen A . Cis-urocanic acid improves cell viability and suppresses inflammasome activation in human retinal pigment epithelial cells . Biochemical Pharmacology . 216 . 115790 . October 2023 . 10.1016/j.bcp.2023.115790 . 37683842 . free .