TY - JOUR
T1 - Knockout of the Bcmo1 gene results in an inflammatory response in female lung, which is suppressed by dietary beta-carotene
AU - Van Helden, Yvonne G.J.
AU - Heil, Sandra G.
AU - Van Schooten, Frederik J.
AU - Kramer, Evelien
AU - Hessel, Susanne
AU - Amengual, Jaume
AU - Ribot, Joan
AU - Teerds, Katja
AU - Wyss, Adrian
AU - Lietz, Georg
AU - Bonet, M. Luisa
AU - Von Lintig, Johannes
AU - Godschalk, Roger W.L.
AU - Keijer, Jaap
N1 - Yvonne van Helden was supported by a grant from NUTRIM/VLAG. This work is part of the research effort of the carotenoid focus team of the European Nutrigenomics Organization (Network of Excellence, EU Contract FOOD-CT-2004-506360) and has been sponsored in part by NuGO. We thank Sophie Alders for her contribution to the histological analysis. Jaap Keijer is a member of Mitofood (COST FA0602). CIBERobn is an initiative of the ISCIII (Spanish government). Adrian Wyss is employed by DSM neutraceuticals and facilitated the use of Bcmo1 mice, BC beadlets, and helped in design of the study. None of the other authors declares any commercial interest. The study results and conclusions were derived independently of any commercial party (in particular DSM Nutritional Products) and were not amended. −/−
PY - 2010/6
Y1 - 2010/6
N2 - 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.
AB - 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.
KW - ADH7
KW - ATBC and CARET study
KW - Beta-carotene 15,15′-monooxygenase 1
KW - Inflammation
KW - LRAT
KW - Vitamin A deficiency
KW - Whole-mouse genome microarray gene expression
UR - https://www.scopus.com/pages/publications/77953028405
UR - https://www.scopus.com/pages/publications/77953028405#tab=citedBy
U2 - 10.1007/s00018-010-0341-7
DO - 10.1007/s00018-010-0341-7
M3 - Article
C2 - 20372966
AN - SCOPUS:77953028405
SN - 1420-682X
VL - 67
SP - 2039
EP - 2056
JO - Cellular and Molecular Life Sciences
JF - Cellular and Molecular Life Sciences
IS - 12
ER -