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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #229198
Title: DIFFERENTIAL EXPRESSION OF CAROTENE-15, 15'-OXYGENASE AND CAROTENE-9', 10'-OXYGENASE IN SELECTED FERRET TISSUES AFTER BETA-CRYPTOXANTHIN SUPPLEMENTATION

Author
item MEIN, JONATHAN - TUFTS UNIVERSITY
item Liu, Chun
item Wang, Xiang-Dong

Submitted to: Carotenoid Symposium
Publication Type: Abstract Only
Publication Acceptance Date: 4/1/2008
Publication Date: 6/22/2008
Citation: Mein, J.R., Liu, C., Wang, X. 2008. Differential expression of carotene-15, 15'-oxygenase and carotene-9', 10'-oxygenase in selected ferret tissues after beta-cryptoxanthin supplementation. In: Carotenoid Science-Abstracts of the Papers Presented at the 15th International Symposium on Carotenoids, June 22-27, 2008. 12:181.

Interpretive Summary:

Technical Abstract: Dietary intake of foods rich in carotenoids, including beta-carotene, beta-cryptoxanthin and lycopene, continue to be associated with a decreased risk of several chronic diseases. While this association continues to persist, the metabolic fate of many carotenoids continues to be elucidated. The carotenoid cleaving enzymes carotene-15, 15'-oxygenase (formally called beta,beta-carotene-15, 15'-monoxygenase, CMO1) and carotene-9', 10'-oxygenase (formally called carotene-9', 10'-monoxygenase, CMO2) have been cloned and characterized in several animal models. The CMO1 gene has been shown to be a PPAR-gamma and RXR responsive gene containing a peroxisome proliferator response element (PPRE) within the promoter region [1]. In contrast, previous studies have failed to identify a putative response element, such as PPRE or RARE, or other enhancer elements within the 5' promoter of the CMO2 gene [2]. Lycopene supplementation has been reported to both increase and decrease CMO2 expression in different animal models. We identified a 4-fold increase in lung CMO2 expression in ferrets [3] whereas a decrease in CMO2 expression in several tissues was reported in F355 rats after lycopene feeding for various time periods [2]. It has been suggested that carotenoid metabolites may regulate CMO2, similar to results seen with beta-carotene metabolites and CMO1. Other than the effects of lycopene feeding on CMO2 expression, which has been inconsistent, no studies have analyzed the mRNA expression of CMO1 and CMO2 in response to carotenoids other than beta-carotene and lycopene. Since the ferret represents a unique model for the investigation of carotenoid metabolism, we have investigated the effect of 9 weeks of beta-cryptoxanthin supplementation on the expression of CMO1 and CMO2 in selected ferret tissues. A total of 18 ferrets were divided into 3 groups: control, low-dose and high-dose beta-cryptoxanthin supplementation. Low-dose animals received 7.5 ug/day while high-dose animals received 37.5 ug/day, which is equivalent to 104 ug and 520 ug/day in humans, respectively. Tissue beta-cryptoxanthin concentrations were determined by HPLC using previously described methods [3]. 1653 base pairs of the ferret CMO1 gene were cloned using reverse transcription and RACE PCR of total ferret RNA. Both CMO1 and CMO2 mRNA expression were analyzed by RT-PCR using the comparative CT method in lung, intestinal mucosa, liver and adipose tissue. HPLC analysis revealed a dose-dependent increase in tissue accumulation of beta-cryptoxanthin. In addition, several unidentified polar compounds were evident upon analysis. Identification of these compounds is ongoing in this laboratory. Real-time analysis revealed differential changes in both CMO1 and CMO2 expression. In the lung, no significant changes in CMO1 expression were evidenced. However, CMO2 expression was significantly decreased in both low- and high-dose supplemented animals compared to controls. In the intestinal mucosa, CMO1 expression was significantly decreased in both low- and high-dose supplemented animals compared to controls; however, there were no changes in CMO2 expression. There were no significant changes in either CMO1 or CMO2 expression in both the liver and adipose tissue; however, a trend toward decreased CMO2 expression was seen in adipose tissue. In conclusion, beta-cryptoxanthin supplementation results in tissue-specific regulation of CMO1 and CMO2 expression. In addition, there was a dose-dependent increase in beta-cryptoxanthin tissue accumulation with putative evidence of metabolite formation.