期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 67, 期 12, 页码 2039-2056出版社
SPRINGER BASEL AG
DOI: 10.1007/s00018-010-0341-7
关键词
ATBC and CARET study; Beta-carotene 15,15 '-monooxygenase 1; Whole-mouse genome microarray gene expression; Inflammation; Vitamin A deficiency; ADH7; LRAT
资金
- NUTRIM/VLAG
- EU [FOOD-CT-2004-506360]
- NuGO
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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