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.
Original language | English |
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Pages (from-to) | 2039-2056 |
Number of pages | 18 |
Journal | Cellular and Molecular Life Sciences |
Volume | 67 |
Issue number | 12 |
DOIs | |
Publication status | Published - Jun 2010 |
Keywords
- ATBC and CARET study
- Beta-carotene 15,15 '-monooxygenase 1
- Whole-mouse genome microarray gene expression
- Inflammation
- Vitamin A deficiency
- ADH7
- LRAT
- NONSTEROIDAL ANTIINFLAMMATORY DRUGS
- VITAMIN-A-DEFICIENCY
- TRANS-RETINOIC ACID
- ALCOHOL-DEHYDROGENASE
- DOUBLE-TRACER
- CANCER
- METABOLISM
- DISEASE
- SUPPLEMENTATION
- IDENTIFICATION