RESUMEN
We examined effects of a major lipotrope, myo-inositol, on the expression of primary glycolytic (glucokinase and phosphofructokinase) and fructolytic enzyme (ketohexokinase [KHK] and aldolase B) genes in the livers of rats fed a control diet, high-sucrose diet, or high-sucrose diet supplemented with 0.5% myo-inositol for 14 d. Supplementation with myo-inositol decreased the hepatic expression of fructolytic enzyme genes, but not that of glycolytic enzyme genes, and the levels of triglycerides, fatty acid synthase, and KHK proteins in high-sucrose diet-induced fatty liver. The study results suggest that myo-inositol represses primary fructlysis, but not glycolysis, in high-sucrose diet-induced fatty liver.
Asunto(s)
Metabolismo de los Hidratos de Carbono/efectos de los fármacos , Sacarosa en la Dieta/efectos adversos , Suplementos Dietéticos , Fructoquinasas/genética , Fructoquinasas/metabolismo , Fructosa-Bifosfato Aldolasa/genética , Fructosa-Bifosfato Aldolasa/metabolismo , Expresión Génica/efectos de los fármacos , Glucoquinasa/genética , Glucoquinasa/metabolismo , Inositol/administración & dosificación , Inositol/farmacología , Hígado/enzimología , Fosfofructoquinasas/genética , Fosfofructoquinasas/metabolismo , Animales , Hígado/metabolismo , Masculino , Ratas WistarAsunto(s)
Neoplasias de la Mama/enzimología , Medicamentos Herbarios Chinos/administración & dosificación , Hexoquinasa/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Glándulas Mamarias Humanas/efectos de los fármacos , Fosfofructoquinasas/genética , Piruvato Quinasa/genética , Animales , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Femenino , Glucólisis/efectos de los fármacos , Hexoquinasa/metabolismo , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Glándulas Mamarias Humanas/enzimología , Glándulas Mamarias Humanas/patología , Fosfofructoquinasas/metabolismo , Piruvato Quinasa/metabolismo , Ratas , Ratas Sprague-Dawley , Crema para la Piel/administración & dosificaciónRESUMEN
This study is to investigate the inhibitory effect and mechanism of prosapogenin A (PSA) on MCF7. MTT assay was performed to determine the inhibitory effect of PSA on MCF7 cells. PI/Hoechst 33342 double staining was used to detect cell apoptosis. RT-PCR was used to test the mRNA levels of STAT3, GLUT1, HK and PFKL. Western blotting was performed to determine the expression of STAT3 and pSTAT3 protein in MCF7 cells. The results showed that PSA could dose-dependently inhibit cell growth of MCF7 followed by IC50 of 9.65 micrmol x L(-1) and promote cell apoptosis of MCF7. Reduced mRNA levels of STAT3, HK and PFKL were observed in MCF7 cells treated with 5 micromol x L(-1) of PSA. PSA also decreased the level of pSTAT3 protein. STAT3 siRNA caused decrease of mRNA of GLUT1, HK and PFKL which indicated STAT3 could regulate the expressions of GLUT1, HK and PFKL. The results suggested that PSA could inhibit cell growth and promote cell apoptosis of MCF7 via inhibition of STAT3 and glycometabolism-related gene.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Proliferación Celular/efectos de los fármacos , Saponinas/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Apoptosis/efectos de los fármacos , Transportador de Glucosa de Tipo 1/genética , Transportador de Glucosa de Tipo 1/metabolismo , Hexoquinasa/genética , Hexoquinasa/metabolismo , Humanos , Células MCF-7 , Fosfofructoquinasas/genética , Fosfofructoquinasas/metabolismo , Plantas Medicinales/química , ARN Mensajero/metabolismo , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Saponinas/aislamiento & purificación , Veratrum/químicaRESUMEN
Plants possess two different types of phosphofructokinases, an ATP-dependent (PFK) and a pyrophosphate-dependent form (PFP). While plant PFPs have been investigated in detail, cDNA clones coding for PFK have not been identified in Arabidopsis thaliana. Searching the A. thaliana genome revealed 11 putative members of a phosphofructokinase gene family. Among those, four sequences showed high homology to the alpha- or beta-subunits of plant PFPs. Seven cDNAs resulted in elevated PFK, but not PFP activity after transient expression in tobacco leaves suggesting that they encode Arabidopsis PFKs. RT-PCR revealed different tissue-specific expression of the individual forms. Furthermore, analysis of GFP fusion proteins indicated their presence in different sub-cellular compartments.