RESUMEN
We investigated the effects of road transportation and administration of the vitamin E and selenium (ESe) on circulating cortisol, haptoglobin, blood metabolites, oxidative biomarkers, white blood cell profiles, and behaviors in pregnant dairy heifers. Forty pregnant Holstein heifers were randomly assigned to one of 4 treatments: no transportation and no ESe administration, no transportation and ESe administration, transportation and no administration, and transportation and ESe administration. The ESe (70 IU/kg dry matter feed of dl-α-tocopheryl acetate and 0.3 mg/kg dry matter feed of sodium selenite) was orally delivered once a day from 7 d before transportation to 3 d after transportation. The heifers were transported in trucks designed for cattle transportation. Blood was collected 1 h before transportation, immediately after transportation (IAT), and at 6, 24, and 48 h after transportation. Behaviors were recorded using a video camera for 2 consecutive days after transportation. Transported/non-ESe-administered heifers had greater cortisol at IAT, haptoglobin at 6 and 24 h after transportation, total oxidative status at 6 h after transportation, and nonesterified fatty acid levels, white blood cell numbers, and neutrophil percentages at IAT and 6 h after transportation in the blood than nontransported heifers. Transported/non-ESe-administered heifers had lower total antioxidative status levels at 48 h after transportation and lymphocyte percentages at IAT and 6 h after transportation than nontransported heifers. Lying time was shorter in transported heifers than nontransported/non-ESe-administered heifers. Transported/ESe-administered heifers had lower cortisol, total oxidative status, nonesterified fatty acid levels at IAT, and haptoglobin concentrations at 6 and 24 h after transportation than transported/non-ESe-administered heifers. Transported/ESe-administered heifers had greater total antioxidative status levels at 48 h after transportation than transported/non-ESe-administered heifers. No ESe administration effects were observed for white blood cell number and neutrophil and lymphocyte percentages and lying time. In conclusion, road transportation caused temporary oxidative stress. Administrating ESe partially alleviated the stress, suggesting that ESe administration could be a viable strategy to reduce stress in transported pregnant heifers, providing a novel role of vitamin E and selenium for improving animal welfare.
Asunto(s)
Selenio , Embarazo , Animales , Bovinos , Femenino , Selenio/farmacología , Hidrocortisona , Haptoglobinas , Vitamina E/farmacología , Antioxidantes/farmacología , Transportes , Ácidos GrasosRESUMEN
"Genome-based precision feeding" is a concept that involves the application of customised diets to different genetic groups of cattle. We investigated the effects of the genomic estimated breeding value (gEBV) and dietary energy to protein ratio (DEP) on growth performance, carcass traits, and lipogenic gene expression in Hanwoo (Korean cattle) steers. Forty-four Hanwoo steers (BWâ¯=â¯636â¯kg, ageâ¯=â¯26.9â¯months) were genotyped using the Illumina Bovine 50â¯K BeadChip. The gEBV was calculated using genomic best linear unbiased prediction. Animals were separated into high gEBV of marbling score or low-gMS groups based on the upper and lower 50% groupings of the reference population, respectively. Animals were assigned to one of four groups in a 2â¯×â¯2 factorial arrangement: high gMS/high DEP (0.084â¯MJ/g), high gMS/low DEP (0.079â¯MJ/g), low gMS/high DEP, and low gMS/low DEP. Steers were fed concentrate with a high or low DEP for 31â¯weeks. The BW tended to be higher (0.05â¯<â¯Pâ¯<â¯0.1) in the high-gMS groups compared to the low-gMS groups at 0, 4, 8, 12, and 20â¯weeks. The average daily gain (ADG) tended to be lower (Pâ¯=â¯0.08) in the high-gMS group than in the low-gMS group. Final BW and measured carcass weight (CW) were positively correlated with the gEBV of carcass weight (gCW). The DEP did not affect ADG. Neither the gMS nor the DEP affected the MS and beef quality grade. The intramuscular fat (IMF) content in the longissimus thoracis (LT) tended to be higher (Pâ¯=â¯0.08) in the high-gMS groups than in the low-gMS groups. The mRNA levels of lipogenic acetyl-CoA carboxylase and fatty acid binding protein 4 genes in the LT were higher (Pâ¯<â¯0.05) in the high-gMS group than in the low-gMS group. Overall, the IMF content tended to be affected by the gMS, and the genetic potential (i.e., gMS) was associated with the functional activity of lipogenic gene expression. The gCW was associated with the measured BW and CW. The results demonstrated that the gMS and the gCW may be used as early prediction indexes for meat quality and growth potential of beef cattle.
Asunto(s)
Genoma , Genómica , Bovinos/genética , Animales , Genómica/métodos , Fenotipo , Genotipo , Carne/análisis , Expresión Génica , Alimentación Animal/análisis , Dieta/veterinaria , Composición Corporal/genéticaRESUMEN
The downstream events and target genes of p53 in the process of senescence are not fully understood. Here, we report a novel function of the forkhead transcription factor Foxp3, which is a key player in mediating T-cell inhibitory functions, in p53-mediated cellular senescence. The overexpression of Foxp3 in mouse embryonic fibroblasts (MEFs) accelerates senescence, whereas Foxp3 knockdown leads to escape from p53-mediated senescence in p53-expressing MEFs. Consistent with these results, Foxp3 expression resulted in the induction of senescence in epithelial cancer cells, including MCF7 and HCT116 cells. Foxp3 overexpression also increased the intracellular levels of reactive oxygen species (ROS). The ROS inhibitor N-acetyl-l-cysteine rescued cells from Foxp3-expression-induced senescence. Furthermore, the elevated ROS levels that accompanied Foxp3 overexpression were paralleled by an increase in p21 expression. Knockdown of p21 in Foxp3-expressing MEFs abrogated the Foxp3-dependent increase in ROS levels, indicating that Foxp3 acts through the induction of p21 and the subsequent ROS elevation to trigger senescence. Collectively, these results suggest that Foxp3 is a downstream target of p53 that is sufficient to induce p21 expression, ROS production and p53-mediated senescence.
Asunto(s)
Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Fibroblastos/citología , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Animales , Línea Celular , Senescencia Celular , Fibroblastos/metabolismo , Regulación de la Expresión Génica , Células HCT116 , Humanos , Células MCF-7 , Ratones , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Transcriptional coactivators SRC-1 and p300 specifically interact with liganded-nuclear receptors and also modulate other transcription factors, including serum response factor (SRF). Here, we report that retinoids repress transactivation by SRF and specific interactions exist between the DNA binding domains of SRF and retinoic acid and retinoid X receptors. We further demonstrate that the repression may involve retinoid-dependent competition for a limiting amount of SRC-1 and p300 between SRF and retinoid receptors. We propose that the well-defined anti-proliferative action of retinoids could, at least in part, result from this novel transrepressive action on the mitogenic transcription factor SRF.
Asunto(s)
Proteínas de Unión al ADN/antagonistas & inhibidores , Proteínas Nucleares/antagonistas & inhibidores , Proteínas Nucleares/fisiología , Transactivadores/fisiología , Factores de Transcripción/fisiología , Activación Transcripcional , Tretinoina/farmacología , Alitretinoína , Animales , División Celular , Células Cultivadas , Proteínas de Unión al ADN/metabolismo , Proteína p300 Asociada a E1A , Células HeLa , Histona Acetiltransferasas , Humanos , Modelos Genéticos , Proteínas Nucleares/metabolismo , Coactivador 1 de Receptor Nuclear , Ratas , Receptores de Ácido Retinoico/metabolismo , Factor de Respuesta SéricaRESUMEN
L-ascorbate (L-ascorbic acid, vitamin C) clearly has an inhibitory effect on cancer cells. However, the mechanism underlying differential sensitivity of cancer cells from same tissue to L-ascorbate is yet to be clarified. Here, we demonstrate that L-ascorbate has a selective killing effect, which is influenced by sodium-dependent vitamin C transporter 2 (SVCT-2) in human breast cancer cells. Treatment of human breast cancer cells with L-ascorbate differentially induced cell death, dependent on the SVCT-2 protein level. Moreover, knockdown of endogenous SVCT-2 via RNA interference in breast cancer cells expressing high levels of the protein induced resistance to L-ascorbate treatment, whereas transfection with SVCT-2 expression plasmids led to enhanced L-ascorbate chemosensitivity. Surprisingly, tumor regression by L-ascorbate administration in mice bearing tumor cell xenograft also corresponded to the SVCT-2 protein level. Interestingly, SVCT-2 expression was absent or weak in normal tissues, but strongly detected in tumor samples obtained from breast cancer patients. In addition, enhanced chemosensitivity to L-ascorbate occurred as a result of caspase-independent autophagy, which was mediated by beclin-1 and LC3 II. In addition, treatment with N-acetyl-L-cysteine, a reactive oxygen species (ROS) scavenger, suppressed the induction of beclin-1 and LC3 II, implying that the differential SVCT-2 protein-dependent L-ascorbate uptake was attributable to intracellular ROS induced by L-ascorbate, subsequently leading to autophagy. These results suggest that functional SVCT-2 sensitizes breast cancer cells to autophagic damage by increasing the L-ascorbate concentration and intracellular ROS production and furthermore, SVCT-2 in breast cancer may act as an indicator for commencing L-ascorbate treatment.
Asunto(s)
Ácido Ascórbico/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Transportadores de Sodio Acoplados a la Vitamina C/fisiología , Acetilcisteína/farmacología , Animales , Ácido Ascórbico/farmacocinética , Autofagia/efectos de los fármacos , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Especies Reactivas de Oxígeno/metabolismo , Transportadores de Sodio Acoplados a la Vitamina C/análisisRESUMEN
Nuclear receptor corepressor (N-CoR) and silencing mediator of retinoid and thyroid hormone receptors (SMRT) form heterogeneous complexes with various histone deacetylases (HDACs). In this report, we found that ER alpha-Delta AF2, a mutant estrogen receptor alpha (ER alpha) deleted for the C-terminal activation function 2 (AF2) core domain, directs estradiol (E(2))-dependent repression and impairs E(2)-induced transactivation by wild type ER alpha. This repression required coexpressed BRG1 in SW-13 cells that lack BRG1, the ATPase constituent of the chromatin-remodeling SWI.SNF complex, and was abolished by HDAC inhibitor trichostatin A. We further demonstrated that ER alpha-Delta AF2 constitutively associates with SMRT but binds DNA in an E(2)-dependent manner in vivo. These results suggest that ER alpha-Delta AF2 and similar mutant receptors recently found associated with certain tumors may actively perturb the normal E(2) signaling via SWI/SNF, N-CoR/SMRT, and HDAC.
Asunto(s)
Silenciador del Gen/fisiología , Receptores de Estrógenos/fisiología , Animales , Células Cultivadas , Chlorocebus aethiops , ADN/efectos de los fármacos , ADN/metabolismo , ADN Helicasas , Proteínas de Unión al ADN/metabolismo , Estradiol/farmacología , Receptor alfa de Estrógeno , Eliminación de Gen , Histona Desacetilasas/fisiología , Humanos , Mutación , Proteínas Nucleares/metabolismo , Proteínas Nucleares/fisiología , Co-Represor 1 de Receptor Nuclear , Co-Represor 2 de Receptor Nuclear , Estructura Terciaria de Proteína , Receptores de Estrógenos/genética , Proteínas Represoras/metabolismo , Transducción de Señal , Factores de Transcripción/fisiología , Células Tumorales CultivadasRESUMEN
Nuclear receptors, many of which undergo a major conformational change upon binding specific ligand, belong to a superfamily of proteins that bind to specific DNA sequences and control gene transcription. They regulate the assembly of a transcriptional preinitiation complex at the promoter of target genes and modulate their expression in response to ligand. In particular, nuclear receptors repress or stimulate transcription by recruiting corepressor or coactivator proteins, in addition to directly contacting the basal transcription machinery. In this review, we discuss recent progress in studies of these transcriptional coregulators of nuclear receptors.
Asunto(s)
Receptores Citoplasmáticos y Nucleares/genética , Receptores Citoplasmáticos y Nucleares/metabolismo , Acetiltransferasas/metabolismo , Animales , Proteínas Portadoras/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Unión al ADN , Histona Acetiltransferasas , Humanos , Complejo Mediador , Modelos Biológicos , Proteínas Nucleares/metabolismo , Co-Represor 1 de Receptor Nuclear , Proteínas de Transporte Nucleocitoplasmático , Proteínas de Unión al ARN , Receptores Citoplasmáticos y Nucleares/química , Proteínas Represoras/metabolismo , Transducción de Señal , Transactivadores/metabolismo , Factores de Transcripción , Transcripción Genética , Factores de Transcripción p300-CBPRESUMEN
Small heterodimer partner (SHP), specifically expressed in liver and a limited number of other tissues, is an unusual orphan nuclear receptor that lacks the conventional DNA binding domain. In this work, we found that SHP expression is abundant in murine macrophage cell line RAW 264.7 but was suppressed by oxidized low density lipoprotein (oxLDL) and its constituent 13-hydroxyoctadecadienoic acid, a ligand for peroxisome proliferator-activated receptor gamma. Furthermore, SHP acted as a transcription coactivator of nuclear factor-kappa B (NF kappa B) and was essential for the previously described NF kappa B transactivation by palmitoyl lysophosphatidylcholine, one of the oxLDL constituents. Accordingly NF kappa B, which was transcriptionally active in the beginning, became progressively inert in oxLDL-treated RAW 264.7 cells as oxLDL decreased the SHP expression. Thus, SHP appears to be an important modulatory component to regulate the transcriptional activities of NF kappa B in oxLDL-treated, resting macrophage cells.