Aldehyde oxidase 1 activity and protein expression in human, rabbit, and pig ocular tissues.

Autor: Hammid A; School of Pharmacy, University of Eastern Finland, Yliopistonranta 1 C, FI-70210 Kuopio, Finland. Electronic address: anam.hammid@uef.fi., Fallon JK; Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Campus Box 7355, Chapel Hill, NC 27599-7355, United States., Vellonen KS; School of Pharmacy, University of Eastern Finland, Yliopistonranta 1 C, FI-70210 Kuopio, Finland., Lassila T; Admescope Ltd, Typpitie 1, FI-90620 Oulu, Finland., Reinisalo M; School of Pharmacy, University of Eastern Finland, Yliopistonranta 1 C, FI-70210 Kuopio, Finland., Urtti A; School of Pharmacy, University of Eastern Finland, Yliopistonranta 1 C, FI-70210 Kuopio, Finland; Faculty of Pharmacy, University of Helsinki, Viikinkaari 5 E, FI-00790 Helsinki, Finland., Gonzalez F; Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; Service of Ophthalmology, University Hospital of Santiago de Compostela, and Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela (FIDIS), 15706 Santiago de Compostela, Spain., Tolonen A; Admescope Ltd, Typpitie 1, FI-90620 Oulu, Finland., Smith PC; Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Campus Box 7355, Chapel Hill, NC 27599-7355, United States., Honkakoski P; School of Pharmacy, University of Eastern Finland, Yliopistonranta 1 C, FI-70210 Kuopio, Finland.
Jazyk: angličtina
Zdroj: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2023 Dec 01; Vol. 191, pp. 106603. Date of Electronic Publication: 2023 Oct 11.
DOI: 10.1016/j.ejps.2023.106603
Abstrakt: Aldehyde oxidase (AOX) is a cytosolic drug-metabolizing enzyme which has attracted increasing attention in drug development due to its high hepatic expression, broad substrate profile and species differences. In contrast, there is limited information on the presence and activity of AOX in extrahepatic tissues including ocular tissues. Because several ocular drugs are potential substrates for AOX, we performed a comprehensive analysis of the AOX1 expression and activity profile in seven ocular tissues from humans, rabbits, and pigs. AOX activities were determined using optimized assays for the established human AOX1 probe substrates 4-dimethylamino-cinnamaldehyde (DMAC) and phthalazine. Inhibition studies were undertaken in conjunctival and retinal homogenates using well-established human AOX1 inhibitors menadione and chlorpromazine. AOX1 protein contents were quantitated with targeted proteomics and confirmed by immunoblotting. Overall, DMAC oxidation rates varied over 10-fold between species (human ˃˃ rabbit ˃ pig) and showed 2- to 6-fold differences between tissues from the same species. Menadione seemed a more potent inhibitor of DMAC oxidation across species than chlorpromazine. Human AOX1 protein levels were highest in the conjunctiva, followed by most posterior tissues, whereas anterior tissues showed low levels. The rabbit AOX1 expression was high in the conjunctiva, retinal pigment epithelial (RPE), and choroid while lower in the anterior tissues. Quantification of pig AOX1 was not successful but immunoblotting confirmed the presence of AOX1 in all species. DMAC oxidation rates and AOX1 contents correlated quite well in humans and rabbits. This study provides, for the first time, insights into the ocular expression and activity of AOX1 among multiple species.
Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest.
(Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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