novel retinoic acid analogue, 7-hydroxy retinoic acid, isolated from cyanobacteria

• Published in: Biochimica et biophysica acta Vol. 1810; no. 4; pp. 414 - 419
• Main Authors: Kaya, Kunimitsu, Shiraishi, Fujio, Uchida, Hideaki, Sano, Tomoharu
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2011
• Subjects: animal tissues; cells; chromatography; fluorescent lighting; high performance liquid chromatography; Humans; isolation techniques; isomerization; isomers; mass spectrometry; metabolites; Microcystis - chemistry; Microcystis aeruginosa; Receptors, Retinoic Acid - agonists; Receptors, Retinoic Acid - metabolism; retinoic acid; Spirulina; Spirulina - chemistry; Tretinoin - analogs & derivatives; Tretinoin - isolation & purification; Tretinoin - pharmacology; Two-Hybrid System Techniques; ultraviolet radiation; vitamin A
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2010.11.009

BACKGROUND: All-trans retinoic acid (RA) is a low-molecular compound derived from vitamin A. It induces events in various ways by binding with the retinoic acid receptor (RAR), a nuclear receptor, in animal cells. RA and its metabolites have been found in animal tissues. In this paper, we report a novel RA analogue found in cyanobacterial cells, describe the method for its isolation, and compare its photo-stability with that of all-trans RA. METHODS: The new A analogue was extracted from cells of Microcystis aeruginosa and Spirulina sp. and fractionated by high-performance liquid chromatography. The analogue was analysed using a yeast two-hybrid assay method to measure in vitro RAR-agonistic activity. Liquid chromatography–mass spectrometry/mass spectrometry analyses was performed to elucidate the chemical structure of this RA analogue. RESULTS: The results of the analysis of the fragments revealed that the novel RA analogue was 7-hydroxy RA. The yields from 3.5μg (4.5% of the total RAR-agonistic activity of Spirulina sp. cells) of 7-hydroxy RA was a mixture of 4 isomers due to cis–trans isomerisation coupled with keto–enol tautomerism; its relative RAR agonistic activity was 0.49±0.01 (n=3) when the activity of all trans RA was set up to 1.00. Under fluorescent light, the mixture of 7-hydroxy RA isomers was more stable than all- trans RA. CONCLUSIONS: We isolated a novel RAR-activating compound, 7-hydroxy RA, from cyanobacteria. GENERAL SIGNIFICANCE: 7-hydroxy RA is more stable than all-trans RA under UV-A.