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1.
Nutr Res ; 33(9): 733-42, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24034573

RESUMEN

Carotene-15,15'-monooxygenase (CMO-I) cleaves ß-carotene to form vitamin A, whereas carotene-9',10'-monooxygenase (CMO-II) preferentially cleaves non-provitamin A carotenoids. Recent reports indicate that ß-carotene metabolites regulate dietary lipid uptake, whereas lycopene regulates peroxisome proliferator-activated receptor expression. To determine the physiologic consequences of carotenoids and their interactions with CMO-I and CMO-II, we characterized mammalian carotenoid metabolism, metabolic perturbations, and lipid metabolism in female CMO-I(-/-) and CMO-II(-/-) mice fed lycopene or tomato-containing diets for 30 days. We hypothesized that there would be significant interactions between diet and genotype on carotenoid accumulation and lipid parameters. CMO-I(-/-) mice had higher levels of leptin, insulin, and hepatic lipidosis but lower levels of serum cholesterol. CMO-II(-/-) mice had increased tissue lycopene and phytofluene accumulation, reduced insulin-like growth factor 1 levels and cholesterol levels, but elevated liver lipids and cholesterol compared with wild-type mice. The diets did not modulate these genotypic perturbations, but lycopene and tomato powder significantly decreased serum insulin-like growth factor 1. Tomato powder also increased hepatic peroxisome proliferator-activated receptor expression, independent of genotype. These data point to the pleiotropic actions of CMO-I and CMO-II supporting a strong role of these proteins in regulating tissue carotenoid accumulation and the lipid metabolic phenotype as well as tomato carotenoid-independent regulation of lipid metabolism.


Asunto(s)
Carotenoides/administración & dosificación , Dieta , Ácido Graso Desaturasas/genética , Metabolismo de los Lípidos/efectos de los fármacos , Solanum lycopersicum/química , beta-Caroteno 15,15'-Monooxigenasa/genética , Tejido Adiposo/metabolismo , Animales , Carotenoides/sangre , Colesterol/sangre , Ácido Graso Desaturasas/metabolismo , Femenino , Genotipo , Hormonas/sangre , Inflamación/patología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Licopeno , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Tamaño de los Órganos , Fenotipo , Polvos/química , ARN Mensajero/genética , ARN Mensajero/metabolismo , beta Caroteno/administración & dosificación , beta Caroteno/sangre , beta-Caroteno 15,15'-Monooxigenasa/metabolismo
2.
Nutr Cancer ; 63(2): 256-63, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21207319

RESUMEN

Lycopene is associated with a reduced risk of prostate cancer. However, lycopene may not be wholly responsible for the effects seen in vivo or in cell culture systems. Apo-lycopenals or other lycopene metabolites, whether produced by cleavage enzymes within the body or consumed with tomato products, can be found in tissues at concentrations equivalent to physiological retinoid concentrations. Therefore, it is plausible that lycopenoids, like retinoids, are bioactive within tissues. Androgen-independent DU145 prostate cancer cells were treated with lycopene, apo-8'-lycopenal, or apo-12'-lycopenal. DU145 cell proliferation was significantly reduced by supra-physiological levels of lycopene and apo-12'-lycopenal, in part, through alteration of the normal cell cycle. Levels of the gap junction protein, connexin 43, were unaltered by lycopene or apo-lycopenal treatment while cell apoptosis rates significantly decreased. We further confirmed that connexin 43 protein levels were unaltered by lycopene treatment in mouse embryonic fibroblasts, or in Dunning R3327-H rat prostate tumor. The present data indicate that lycopene and apo-12'-lycopenal reduce the proliferation of prostate cancer cells, in part, by inhibiting normal cell cycle progression.


Asunto(s)
Aldehídos/farmacología , Anticarcinógenos/farmacología , Carotenoides/farmacología , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Neoplasias de la Próstata/patología , Terpenos/farmacología , Análisis de Varianza , Animales , Apoptosis , Células Cultivadas , Progresión de la Enfermedad , Fibroblastos/efectos de los fármacos , Humanos , Licopeno , Solanum lycopersicum/química , Masculino , Ratones , Ratas , Retinoides/química
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