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Knockout of the Bcmo1 gene results in an inflammatory response in female lung, which is suppressed by dietary beta-carotene.

van Helden YG, Heil SG, van Schooten FJ, Kramer E, Hessel S, Amengual J, Ribot J, Teerds K, Wyss A, Lietz G, Bonet ML, von Lintig J, Godschalk RW, Keijer J - Cell. Mol. Life Sci. (2010)

Bottom Line: Bcmo1 (-/-) mice are therefore suitable to investigate BC-induced alterations in gene expression in lung, assessed by microarray analysis.Supported by metabolite and gene-expression data, we hypothesize that the increased inflammatory response is due to an altered BC metabolism, resulting in an increased vitamin A requirement in Bcmo1 (-/-) mice.This suggests that effects of BC may depend on inter-individual variations in BC-metabolizing enzymes, such as the frequently occurring human polymorphisms in BCMO1.

View Article: PubMed Central - PubMed

Affiliation: Department of Human and Animal Physiology, Wageningen University, PO Box 338, 6700 AH, Wageningen, The Netherlands.

ABSTRACT
Beta-carotene 15,15'-monooxygenase 1 knockout (Bcmo1 (-/-)) mice accumulate beta-carotene (BC) similarly to humans, whereas wild-type (Bcmo1 (+/+)) mice efficiently cleave BC. Bcmo1 (-/-) mice are therefore suitable to investigate BC-induced alterations in gene expression in lung, assessed by microarray analysis. Bcmo1 (-/-) mice receiving control diet had increased expression of inflammatory genes as compared to BC-supplemented Bcmo1 (-/-) mice and Bcmo1 (+/+) mice that received either control or BC-supplemented diets. Differential gene expression in Bcmo1 (-/-) mice was confirmed by real-time quantitative PCR. Histochemical analysis indeed showed an increase in inflammatory cells in lungs of control Bcmo1 (-/-) mice. Supported by metabolite and gene-expression data, we hypothesize that the increased inflammatory response is due to an altered BC metabolism, resulting in an increased vitamin A requirement in Bcmo1 (-/-) mice. This suggests that effects of BC may depend on inter-individual variations in BC-metabolizing enzymes, such as the frequently occurring human polymorphisms in BCMO1.

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Correlation of BC and BC metabolite concentrations in lung. Correlation of a BC concentration and retinyl ester concentration (Bcmo1+/+: R = 0.90, p < 0.001; Bcmo1−/−: R = 0.87, p < 0.001) and b BC concentration and retinol concentration (Bcmo1+/+: R = 0.46, p = 0.13; Bcmo1−/−: R = 0.52, p = 0.10) in lungs of Bcmo1+/+ mice (open circles) and Bcmo1−/− mice (closed circles)
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Fig7: Correlation of BC and BC metabolite concentrations in lung. Correlation of a BC concentration and retinyl ester concentration (Bcmo1+/+: R = 0.90, p < 0.001; Bcmo1−/−: R = 0.87, p < 0.001) and b BC concentration and retinol concentration (Bcmo1+/+: R = 0.46, p = 0.13; Bcmo1−/−: R = 0.52, p = 0.10) in lungs of Bcmo1+/+ mice (open circles) and Bcmo1−/− mice (closed circles)

Mentions: To further investigate whether a lack of BC or BC metabolites could explain the transcriptional and histological increased inflammatory response in the Bcmo1−/− control mice, we investigated changes in downstream BC metabolism. First, we evaluated correlations between BC, retinol and retinyl ester concentrations in mouse lung. There was a significant positive correlation between retinyl ester and BC concentrations in lung tissue of Bcmo1+/+ mice (R = 0.90, p < 0.001) (Fig. 7a) with a much lower slope in the Bcmo1−/− mice (R = 0.87, p < 0.001). There was no significant correlation between retinol and BC concentrations in lung tissue of both Bcmo1+/+ as well as in Bcmo1−/− mice (R = 0.46, p = 0.13 and R = 0.52, p = 0.10) (Fig. 7b).Fig. 7


Knockout of the Bcmo1 gene results in an inflammatory response in female lung, which is suppressed by dietary beta-carotene.

van Helden YG, Heil SG, van Schooten FJ, Kramer E, Hessel S, Amengual J, Ribot J, Teerds K, Wyss A, Lietz G, Bonet ML, von Lintig J, Godschalk RW, Keijer J - Cell. Mol. Life Sci. (2010)

Correlation of BC and BC metabolite concentrations in lung. Correlation of a BC concentration and retinyl ester concentration (Bcmo1+/+: R = 0.90, p < 0.001; Bcmo1−/−: R = 0.87, p < 0.001) and b BC concentration and retinol concentration (Bcmo1+/+: R = 0.46, p = 0.13; Bcmo1−/−: R = 0.52, p = 0.10) in lungs of Bcmo1+/+ mice (open circles) and Bcmo1−/− mice (closed circles)
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2877315&req=5

Fig7: Correlation of BC and BC metabolite concentrations in lung. Correlation of a BC concentration and retinyl ester concentration (Bcmo1+/+: R = 0.90, p < 0.001; Bcmo1−/−: R = 0.87, p < 0.001) and b BC concentration and retinol concentration (Bcmo1+/+: R = 0.46, p = 0.13; Bcmo1−/−: R = 0.52, p = 0.10) in lungs of Bcmo1+/+ mice (open circles) and Bcmo1−/− mice (closed circles)
Mentions: To further investigate whether a lack of BC or BC metabolites could explain the transcriptional and histological increased inflammatory response in the Bcmo1−/− control mice, we investigated changes in downstream BC metabolism. First, we evaluated correlations between BC, retinol and retinyl ester concentrations in mouse lung. There was a significant positive correlation between retinyl ester and BC concentrations in lung tissue of Bcmo1+/+ mice (R = 0.90, p < 0.001) (Fig. 7a) with a much lower slope in the Bcmo1−/− mice (R = 0.87, p < 0.001). There was no significant correlation between retinol and BC concentrations in lung tissue of both Bcmo1+/+ as well as in Bcmo1−/− mice (R = 0.46, p = 0.13 and R = 0.52, p = 0.10) (Fig. 7b).Fig. 7

Bottom Line: Bcmo1 (-/-) mice are therefore suitable to investigate BC-induced alterations in gene expression in lung, assessed by microarray analysis.Supported by metabolite and gene-expression data, we hypothesize that the increased inflammatory response is due to an altered BC metabolism, resulting in an increased vitamin A requirement in Bcmo1 (-/-) mice.This suggests that effects of BC may depend on inter-individual variations in BC-metabolizing enzymes, such as the frequently occurring human polymorphisms in BCMO1.

View Article: PubMed Central - PubMed

Affiliation: Department of Human and Animal Physiology, Wageningen University, PO Box 338, 6700 AH, Wageningen, The Netherlands.

ABSTRACT
Beta-carotene 15,15'-monooxygenase 1 knockout (Bcmo1 (-/-)) mice accumulate beta-carotene (BC) similarly to humans, whereas wild-type (Bcmo1 (+/+)) mice efficiently cleave BC. Bcmo1 (-/-) mice are therefore suitable to investigate BC-induced alterations in gene expression in lung, assessed by microarray analysis. Bcmo1 (-/-) mice receiving control diet had increased expression of inflammatory genes as compared to BC-supplemented Bcmo1 (-/-) mice and Bcmo1 (+/+) mice that received either control or BC-supplemented diets. Differential gene expression in Bcmo1 (-/-) mice was confirmed by real-time quantitative PCR. Histochemical analysis indeed showed an increase in inflammatory cells in lungs of control Bcmo1 (-/-) mice. Supported by metabolite and gene-expression data, we hypothesize that the increased inflammatory response is due to an altered BC metabolism, resulting in an increased vitamin A requirement in Bcmo1 (-/-) mice. This suggests that effects of BC may depend on inter-individual variations in BC-metabolizing enzymes, such as the frequently occurring human polymorphisms in BCMO1.

Show MeSH
Related in: MedlinePlus