Dataset Information

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

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.

SUBMITTER: van Helden YG

PROVIDER: S-EPMC2877315 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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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 Yvonne G J YG Heil Sandra G SG van Schooten Frederik J FJ Kramer Evelien E Hessel Susanne S Amengual Jaume J Ribot Joan J Teerds Katja K Wyss Adrian A Lietz Georg G Bonet M Luisa ML von Lintig Johannes J Godschalk Roger W L RW Keijer Jaap J

Cellular and molecular life sciences : CMLS 20100406 12

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 ...[more]

PMID: 20372966

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Project description:Dairy farming in tropical climates is challenging as heat stress can impair reproduction in cows. Previous studies have demonstrated the beneficial effects of beta-carotene supplementation on bovine reproductive performance. This study was performed in Thailand, where the temperature-humidity index (THI) during the experimental periods was measured to range from 78.4 to 86.1. Lactating Holstein cows classified as repeat breeders (previous artificial insemination [AI] failures) were randomly assigned into two treatments, control treatment (T1; received placebo, n = 200) and test treatment (T2; received 400 mg/h/day of beta-carotene, n = 200). All cows were subjected to a protocol for synchronization of ovulation and timed artificial insemination (TAI). The day of the 1st ovulation synchronized protocol was defined as day 0, and the total experimental period was 160 days. Daily placebo or beta-carotene supplements were given orally on day 0 and each subsequent day of the experiment. Diagnosis of pregnancy was performed using ultrasound on day 30 after insemination. Non-pregnant cows were subjected to further ovulation synchronizations (maximum of four) and TAI over a period of 160 days. Milk samples were collected every ten days throughout the experiment. The samples were analyzed for beta-carotene concentration, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. The pregnancies per AI of the cows in T2 were significantly greater than that of T1 from the 2nd to 4th TAI. During the entire experimental period, the pregnancies in T2 were significantly greater than that of T1. Cox's proportional hazards regression model data indicated a 44% greater probability of pregnancy for cows receiving beta-carotene. The concentrations of milk beta-carotene in T2 were significantly greater than T1 from the 2nd to 4th TAI. Significantly greater SOD and GPx activities were observed in T2 than T1, suggesting a reduction of oxidative stress in cows treated with beta-carotene. Dietary supplementation with beta-carotene thus improves the reproductive performance of repeat breeders exposed to heat stress, possibly by reducing oxidative stress.

Project description:β-carotene is known to have pharmacological effects such as anti-inflammatory, antioxidant, and anti-tumor properties. However, its main mechanism and related signaling pathways in the treatment of inflammation are still unclear. In this study, component target prediction was performed by using literature retrieval and the SwissTargetPrediction database. Disease targets were collected from various databases, including DisGeNET, OMIM, Drug Bank, and GeneCards. A protein-protein interaction (PPI) network was constructed, and enrichment analysis of gene ontology and biological pathways was carried out for important targets. The analysis showed that there were 191 unique targets of β-carotene after removing repeat sites. A total of 2067 targets from the three databases were integrated, 58 duplicate targets were removed, and 2009 potential disease action targets were obtained. Biological function enrichment analysis revealed 284 biological process (BP) entries, 31 cellular component (CC) entries, 55 molecular function (MF) entries, and 84 cellular pathways. The biological processes were mostly associated with various pathways and their regulation, whereas the cell components were mainly membrane components. The main molecular functions included RNA polymerase II transcription factor activity, DNA binding specific to the ligand activation sequence, DNA binding, steroid binding sequence-specific DNA binding, enzyme binding, and steroid hormone receptors. The pathways involved in the process included the TNF signaling pathway, sphingomyelin signaling pathway, and some disease pathways. Lastly, the anti-inflammatory signaling pathway of β-carotene was systematically analyzed using network pharmacology, while the molecular mechanism of β-carotene was further explored by molecular docking. In this study, the anti-inflammatory mechanism of β-carotene was preliminarily explored and predicted by bioinformatics methods, and further experiments will be designed to verify and confirm the predicted results, in order to finally reveal the anti-inflammatory mechanism of β-carotene.

Dataset Information

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

Publications

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

Similar Datasets

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