Retinol up-regulates the receptor for advanced glycation endproducts (RAGE) by increasing intracellular reactive species.
Retinol (vitamin A) and other retinoids have been suggested to exert an important antioxidant function in biological systems, besides their more established role as regulators of cell growth and differentiation. On the other hand, many authors have recently observed pro-oxidant activities of vitamin A and other retinoids in vitro and in vivo, resulting in cell death and/or transformation associated to increased oxidative damage. However, the mechanisms by which retinol causes oxidative stress are still not fully understood. Receptors for advanced glycation endproducts (RAGE) have been recently implied as promoters and/or amplifiers of oxidant-mediated cell death induced by diverse agents, and increased RAGE expression is observed in conditions related to unbalanced production of reactive species, such as in atherosclerosis and neurodegeneration. In the present work, we observed that retinol supplementation increases RAGE protein expression in cultured Sertoli cells, and antioxidant co-treatment reversed this effect. Retinol-increased RAGE expression was observed only at concentrations that induce intracellular reactive species production, as assessed by the DCFH assay. These results indicate that retinol is able to increase RAGE expression by an oxidant-dependent mechanism, and suggest that RAGE signaling may be involved in some of the deleterious effects observed in some retinol-supplementation therapies.
Gelain
Daniel Pens
DP
Centro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Laboratório 32, Rua Ramiro Barcelos 2600 anexo, CEP 90035-003, Porto Alegre, RS, Brazil. dgelain@yahoo.com.br
de Bittencourt Pasquali
Matheus Augusto
MA
Caregnato
Fernanda Freitas
FF
Zanotto-Filho
Alfeu
A
Moreira
José Cláudio Fonseca
JC
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005452:Fluoresceins / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D005609:Free Radicals / Q000032:analysis; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D012708:Sertoli Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation; D014801:Vitamin A / Q000494:pharmacology*; D014815:Vitamins / Q000494:pharmacology*
D000975:Antioxidants; D002839:Chromans; D004338:Drug Combinations; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005609:Free Radicals; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014815:Vitamins; D014801:Vitamin A; C029569:diacetyldichlorofluorescein; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid