Cloning and Functional Studies of a Splice Variant of CYP26B1 Expressed in Vascular Cells

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Título

Cloning and Functional Studies of a Splice Variant of CYP26B1 Expressed in Vascular Cells

Tema

ACIDO TRANS-RETINOICO
CLONACION MOLECULAR
BIBLIOGRAFIA NACIONAL QUIMICA
2012
CELULAS VASCULARES

Abstract

Background: All-trans retinoic acid (atRA) plays an essential role in the regulation of gene expression, cell growth and differentiation and is also important for normal cardiovascular development but may in turn be involved in cardiovascular diseases, i.e. atherosclerosis and restenosis. The cellular atRA levels are under strict control involving several cytochromes P450 isoforms (CYPs). CYP26 may be the most important regulator of atRA catabolism in vascular cells. The present study describes the molecular cloning, characterization and function of atRA-induced expression of a spliced variant of the CYP26B1 gene.
Methodology/Principal Findings: The coding region of the spliced CYP26B1 lacking exon 2 was amplified from cDNA synthesized from atRA-treated human aortic smooth muscle cells and sequenced. Both the spliced variant and full length CYP26B1 was found to be expressed in cultured human endothelial and smooth muscle cells, and in normal and atherosclerotic vessel. atRA induced both variants of CYP26B1 in cultured vascular cells. Furthermore, the levels of spliced mRNA transcript were 4.5 times higher in the atherosclerotic lesion compared to normal arteries and the expression in the lesions was increased 20-fold upon atRA treatment. The spliced CYP26B1 still has the capability to degrade atRA, but at an initial rate one-third that of the corresponding full length enzyme. Transfection of COS-1 and THP-1 cells with the CYP26B1 spliced variant indicated either an increase or a decrease in the catabolism of atRA, probably depending on the expression
of other atRA catabolizing enzymes in the cells.
Conclusions/Significance: Vascular cells express the spliced variant of CYP26B1 lacking exon 2 and it is also increased in atherosclerotic lesions. The spliced variant displays a slower and reduced degradation of atRA as compared to the fulllength enzyme. Further studies are needed, however, to clarify the substrate specificity and role of the CYP26B1 splice variant in health and disease.

 

Autor

Elmabsout, A. A.
Kumawat, A.
Krivospitskaya, O
Savenstrand, H
Olofsson, P. S.
Eriksson, L. A.
Strid, A
Valen, G.
Torma,  H.
Sirsjo, A

Fuente

PloS One v. 7, no. 5, 2012. -- e36839

Editor

de Windt, Leon J.

Fecha

2012

Derechos

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PDF

Idioma

Inglés

Tipo

Artículo

Identificador

doi:10.1371/journal.pone.0036839

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Original Format

PDF
Fecha de agregación
August 10, 2012
Colección
Bibliografía Nacional Química
Tipo de Elemento
Document
Etiquetas
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Citación
Elmabsout, A. A., “Cloning and Functional Studies of a Splice Variant of CYP26B1 Expressed in Vascular Cells,” RIQUIM - Repositorio Institucional de la Facultad de Química - UdelaR, accessed August 21, 2019, http://riquim.fq.edu.uy/items/show/53.
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