Is FICZ a key molecule for fitness and longevity?

The biological roles of the aryl hydrocarbon receptor (AHR, earlier called the dioxin receptor) are finally being clarified. Ulf Rannug has published two new reviews, one of the articles summarizes the chemistry and properties of all known indolocarbazoles.The other review is focused on the endogenous functions of this receptor and its activation by the tryptophan-derived compound 6-formylindolo[3,2-b]carbazole, FICZ. This signal molecule, which Ulf and Agneta Rannug originally identified and described as the most potent AHR activator, seems to play a critical role in normal physiological processes. Also, its impact on the severity of immune diseases and cancer in animal models is remarkable.

The tryptophan derivative 6-formylindolo[3,2-b]carbazole, FICZ, a dynamic mediator of endogenous aryl hydrocarbon receptor signaling, balances cell growth and differentiation. Rannug A, Rannug U. Crit Rev Toxicol. 2018 Sep 18:1-20. doi: 10.1080/10408444.2018.1493086. [Epub ahead of print] PMID: 30226107

This paper has been recommended in F1000Prime as being of special significance in its field by F1000 Faculty

Chemistry and Properties of Indolocarbazoles. Janosik T, Rannug A, Rannug U, Wahlström N, Slätt J, Bergman J.Chem Rev. 2018 Sep 7. doi: 10.1021/acs.chemrev.8b00186. [Epub ahead of print] PMID: 30191712

 

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Selected publications

Smirnova A, Wincent E, Vikström Bergander L, Alsberg T, Bergman J, Rannug A, Rannug U. Evidence for New Light-Independent Pathways for Generation of the Endogenous Aryl Hydrocarbon Receptor Agonist FICZ. Chem Res Toxicol. 2016 Jan 19;29(1):75-86. doi: 10.1021/acs.chemrestox.5b00416. Epub 2015 Dec 30.

Mohammadi-Bardbori A, Vikström Bergander L, Rannug U, Rannug A. NADPH Oxidase-Dependent Mechanism Explains How Arsenic and Other Oxidants Can Activate Aryl Hydrocarbon Receptor Signaling. Chem Res Toxicol. 2015 Dec 21;28(12):2278-86. doi: 10.1021/acs.chemrestox.5b00415. Epub 2015 Nov 16.

Wincent E, Bengtsson J, Mohammadi Bardbori A, Alsberg T, Luecke S, Rannug U, Rannug A. Inhibition of cytochrome P4501-dependent clearance of the endogenous agonist FICZ as a mechanism for activation of the aryl hydrocarbon receptor. Proc Natl Acad Sci U S A. 2012 Mar 20;109(12):4479-84. doi: 10.1073/pnas.1118467109. Epub 2012 Mar 5.

Wincent E, Amini N, Luecke S, Glatt H, Bergman J, Crescenzi C, Rannug A, Rannug U. The suggested physiologic aryl hydrocarbon receptor activator and cytochrome P4501 substrate 6-formylindolo[3,2-b]carbazole is present in humans. J Biol Chem. 2009 Jan 30;284(5):2690-6. doi: 10.1074/jbc.M808321200. Epub 2008 Dec 2.

Rannug A, Rannug U, Rosenkranz HS, Winqvist L, Westerholm R, Agurell E, Grafström AK. Certain photooxidized derivatives of tryptophan bind with very high affinity to the Ah receptor and are likely to be endogenous signal substances. J Biol Chem. 1987 Nov 15;262(32):15422-7.

 

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