Metabolism of Natural Retinoids in Psoriatic Epidermis

Siegenthaler, Georges; Gumowski‐Sunek, D.; Saurat, J.‐H.

doi:10.1111/1523-1747.ep12505769

Cited by 26 publications

(15 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…5], corresponds to the increase of the C R A B P -II iso form and is accounted for by the preferential overexpres sion of the C R A B P -II gene. We have previously found that in LPS there is an increase in the enzymatic activity that transforms retinol into retinoic acid [16]; this should result in a higher production of retinoic acid in L P S. thus to a higher amount of available retinoic acid in the cell. It is likely that the two phenomena -i.e.…”

Section: R a B P -Ii Is Overexpressed In Lesional Psoriatic Skinmentioning

confidence: 97%

Overexpression of Cellular Retinoic Acid-Binding Protein Type II (CRABP-II) and Down-Regulation of CRABP-I in Psoriatic Skin

et al. 1992

View full text Add to dashboard Cite

Cellular retinoic acid-binding proteins (CRABPs) might exert a physiological function by controlling the intracellular levels of free retinoic acid. The aim of this study was to analyze the relative expression of CRABP-I and CRABP-II in lesional (LPS) and nonlesional (NLPS) psoriatic skin. CRABP-I and -II proteins were analyzed by a PAGE-autoradioblotting technique, and their respective mRNA were studied by RNA blot and in situ hybridization. We found that CRABP-II levels were 6-fold higher in LPS and 2-fold in NLPS as compared to normal skin, whereas CRABP-I levels were decreased in NLPS and LPS. CRABP-II mRNA were grossly overexpressed in all LPS and some NLPS specimens. These results indicate a switch to the overexpression of CRABP-II mRNA in psoriasis which induces high levels of the protein mainly in LPS; these observations may be relevant to the pathophysiology and therapy of psoriasis as CRABP-I and -II have different ligand-binding affinities.

show abstract

Section: R a B P -Ii Is Overexpressed In Lesional Psoriatic Skinmentioning

confidence: 97%

Overexpression of Cellular Retinoic Acid-Binding Protein Type II (CRABP-II) and Down-Regulation of CRABP-I in Psoriatic Skin

et al. 1992

View full text Add to dashboard Cite

show abstract

“…However, the physiological roles of these enzymes are still unknown. Possible roles include homeostatic control of vitamins such as retinoids and other biologically active molecules, and elimination of biogenic wastes or breakdown products generated by ultraviolet radiation and other environmental stresses (Kishore and Boutwell, 1980;Siegenthaler et al, 1990;Beedham et al, 1995;Garattini et al, 2003). The present study has demonstrated that nitroreductase activities toward some nitro-PAHs in skin of various mammalian species are due to both aldehyde oxidase and xanthine oxidoreductase, and the species differences reflect differences of relative aldehyde oxidase and xanthine oxidoreductase activities.…”

Section: Discussionmentioning

confidence: 50%

Involvement of Molybdenum Hydroxylases in Reductive Metabolism of Nitro Polycyclic Aromatic Hydrocarbons in Mammalian Skin

Ueda

Sugihara²,

Ohta³

et al. 2005

Drug Metab Dispos

View full text Add to dashboard Cite

ABSTRACT:Molybdenum hydroxylases, aldehyde oxidase and xanthine oxidoreductase, were shown to be involved in the nitroreduction of 2-nitrofluorene (NF), 1-nitropyrene, and 4-nitrobiphenyl, environmental pollutants, in the skin of various mammalian species. NF was reduced to 2-aminofluorene by hamster skin cytosol in the presence of 2-hydroxypyrimidine, 4-hydroxypyrimidine, N 1 -methylnicotinamide, or benzaldehyde, but not hypoxanthine or xanthine. Inhibitors of aldehyde oxidase markedly inhibited these nitroreductase activities, but oxypurinol, an inhibitor of xanthine oxidoreductase, had little effect. In DEAE column chromatography of hamster skin cytosol, the major fraction exhibiting nitroreductase activity also showed aldehyde oxidase activity. 2-Hydroxypyrimidine-linked nitroreductase activities of skin cytosol from rabbits and guinea pigs were also inhibited by an inhibitor of aldehyde oxidase. In contrast, nitroreductase activities of skin cytosols of rats and mice were markedly inhibited by oxypurinol. When aldehyde oxidase activity was estimated in skin cytosol of various mammals using benzaldehyde oxidase activity as a marker, considerable variability of the activity was found. The highest activity was observed with hamsters, and the lowest activity with rats. On the other hand, the highest xanthine oxidoreductase activity was observed with rats, and the lowest activity with rabbits. These skin cytosols of various mammals also exhibited significant 2-hydroxypyrimidine-linked nitroreductase activities toward 1-nitropyrene and 4-nitrobiphenyl catalyzed by aldehyde oxidase and xanthine oxidoreductase. Thus, NF was mainly reduced by aldehyde oxidase and xanthine oxidoreductase in skins of animals. However, the contributions of these two molybdenum hydroxylases were considerably different among animal species.

show abstract

“…Psoriasis involves altered vitamin A metabolism resulting in high levels of retinoic acid in psoriatic plaques compared to normal skin . Thus the fact that retinoid therapy is effective for psoriasis treatment appears to represent a paradox.…”

Section: Pharmacologymentioning

confidence: 99%

“…Psoriasis involves altered vitamin A metabolism resulting in high levels of retinoic acid in psoriatic plaques compared to normal skin. 12 Thus the fact that retinoid therapy is effective for psoriasis treatment appears to represent a paradox. Acitretin has multiple effects on epidermal cell growth and differentiation possibly responsible for its therapeutic action in psoriasis.…”

Section: Pharmacologymentioning

confidence: 99%

Acitretin in psoriasis: an evolving scenario

Dogra

Yadav

2014

Int J Dermatology

View full text Add to dashboard Cite

Acitretin, an active metabolite of etretinate, is the most widely used systemic retinoid in the treatment of psoriasis. There are several unique characteristics of this drug, which set it apart from other options in the therapeutic armamentarium of psoriasis. It is highly efficacious as monotherapy in some specific clinical subtypes of psoriasis. It has dose-sparing effects when used as combination therapy with conventional systemic drugs as well as the biologics. It is a good option for long-term maintenance therapy. Side effects are common but usually mild and can be managed by its proper dosing and monitoring. With appropriate patient selection, gradual dose escalation, and patient counseling, we can deliver good results in psoriasis with this useful drug. This review gives a comprehensive recount of acitretin use in the present era of biologics in psoriasis.

show abstract

Metabolism of Natural Retinoids in Psoriatic Epidermis

Cited by 26 publications

References 11 publications

Overexpression of Cellular Retinoic Acid-Binding Protein Type II (CRABP-II) and Down-Regulation of CRABP-I in Psoriatic Skin

Overexpression of Cellular Retinoic Acid-Binding Protein Type II (CRABP-II) and Down-Regulation of CRABP-I in Psoriatic Skin

Involvement of Molybdenum Hydroxylases in Reductive Metabolism of Nitro Polycyclic Aromatic Hydrocarbons in Mammalian Skin

Acitretin in psoriasis: an evolving scenario

Contact Info

Product

Resources

About