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- Elmabsout, Ali Ateia, et al.
(author)
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Cloning and Functional Studies of a Splice Variant of CYP26B1 Expressed in Vascular Cells
- 2012
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In: Plos One. - San Francisco, USA : Public Library of Science (PLoS). - 1932-6203. ; 7:5
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Journal article (peer-reviewed)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 full-length enzyme. Further studies are needed, however, to clarify the substrate specificity and role of the CYP26B1 splice variant in health and disease.
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- Fagan, V., et al.
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COMPARE analysis of the toxicity of an iminoquinone derivative of the imidazo[5,4-f]benzimidazoles with NAD(P)H:quinone Oxidoreductase 1 (NQO1) activity and computational docking of quinones as NQO1 substrates
- 2012
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In: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 20:10, s. 3223-3232
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Journal article (peer-reviewed)abstract
- Synthesis and cytotoxicity of imidazo[5,4-f]benzimidazolequinones and iminoquinone derivatives is described, enabling structure-activity relationships to be obtained. The most promising compound (an iminoquinone derivative) has undergone National Cancer Institute (NCI) 60 cell line (single and five dose) screening, and using the NCI COMPARE program, has shown correlation to NQO1 activity and to other NQO1 substrates. Common structural features suggest that the iminoquinone moiety is significant with regard to NQO1 specificity. Computational docking into the active site of NQO1 was performed, and the first comprehensive mitomycin C (MMC)-NQO1 docking study is presented. Small distances for hydride reduction and high binding affinities are characteristic of MMC and of iminoquinones showing correlations with NQO1 via COMPARE analysis. Docking also indicated that the presence of a substituent capable of hydrogen bonding to the His194 residue is important in influencing the orientation of the substrate in the NQO1 active site, leading to more efficient reduction. (C) 2012 Elsevier Ltd. All rights reserved.
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- Haque, M. Atiqul, et al.
(author)
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Bangladeshi school-age children's experiences and perceptions on child maltreatment : A qualitative interview study
- 2017
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In: Child Care Health and Development. - : John Wiley & Sons. - 0305-1862 .- 1365-2214. ; 43:6, s. 876-883
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Journal article (peer-reviewed)abstract
- BackgroundChild maltreatment (CM) is a public health problem and is recognized as a huge barrier for child development. Most of the research and definitions on CM are from the perspective of high-income western countries. Because no major studies have been conducted on CM in Bangladesh, the aim of the current study was to explore the experiences of and perceptions on CM in school-age children in rural and urban Bangladesh in order to understand maltreatment in a local context and from a child perspective. MethodsSemistructured individual interviews with 24 children (13 boys and 11 girls), between the ages of 9 and 13years of which 11 were schoolgoing and 13 non-schoolgoing, were conducted during July 2013 and analysed according to qualitative content analysis. ResultsCM was a common and painful experience with serious physical and emotional consequences but highly accepted by the society. Vulnerable groups were especially young children, girls, and poor children. The children's voices were not heard due to their low status and low position in their families, schools, and working places. The main theme that emerged in the analysis was children's subordination, which permeated the five categories: (a) perception of children's situation in society, (b) understanding children's development and needs, (c) CM associated to school achievement, (d) negative impact of CM, and (e) emotional responses. ConclusionsDifferent kinds of abuse are obviously common in Bangladesh, and the schools do not follow the law from 2011 prohibiting corporal punishment at school. The society has to take further steps to live up to the UN Convention on the Rights of the Child, which was ratified already in 1990, to protect the Bangladeshi children from CM.
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