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1.
Curr Issues Mol Biol ; 46(2): 1078-1090, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38392186

RESUMEN

Diabetes is caused by abnormal glucose metabolism, and muscle, the largest tissue in the human body, is largely involved. Urolithin A (UroA) is a major intestinal and microbial metabolite of ellagic acid and ellagitannins and is found in fruits such as strawberry and pomegranate. In this present study, we investigated the antidiabetic effects of UroA in L6 myotubes and in KK-Ay/Ta, a mouse model of type 2 diabetes (T2D). UroA treatment elevated the glucose uptake (GU) of L6 myotubes in the absence of insulin. This elevation in GU by UroA treatment was partially inhibited by the concurrent addition of LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K) which activates Akt (PKB: protein kinase B) or Compound C, an inhibitor of 5'-adenosine monophosphate-activated protein kinase (AMPK). Moreover, UroA was found to activate both pathways of Akt and AMPK, and then to promote translocation of glucose transporter 4 (GLUT4) from the cytosol to the plasma membrane in L6 myotubes. Based on these in vitro findings, an intraperitoneal glucose tolerance test (IPGTT) was performed after the oral administration of UroA for 3 weeks to KK-Ay/Ta mice with glucose intolerance. UroA was demonstrated to alleviate glucose intolerance. These results suggest that UroA is a biofactor with antihyperglycemic effects in the T2D state.

2.
Biosci Biotechnol Biochem ; 88(8): 966-978, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-38772744

RESUMEN

The NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome triggers the maturation of interleukin-1ß (IL-1ß) and is implicated in the pathogenesis of various inflammatory diseases. Urolithin A, a gut microbial metabolite of ellagic acid, reportedly exerts antiinflammatory effects in vitro and in vivo. However, whether urolithin A suppresses NLRP3 inflammasome activation is unclear. In this study, urolithin A inhibited the cleavage of NLRP3 inflammasome agonist-induced caspase-1, maturation of IL-1ß, and activation of pyroptosis in lipopolysaccharide-primed mouse bone marrow-derived macrophages. Urolithin A reduced generation of intracellular and mitochondrial reactive oxygen species (ROS) and restricted the interaction between thioredoxin-interacting protein and NLRP3, which attenuated NLRP3 inflammasome activation. Urolithin A administration prevented monosodium urate-induced peritonitis in mice. Collectively, these findings indicate that urolithin A suppresses NLRP3 inflammasome activation, at least partially, by repressing the generation of intracellular and mitochondrial ROS.


Asunto(s)
Cumarinas , Inflamasomas , Interleucina-1beta , Proteína con Dominio Pirina 3 de la Familia NLR , Peritonitis , Especies Reactivas de Oxígeno , Ácido Úrico , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Cumarinas/farmacología , Cumarinas/química , Especies Reactivas de Oxígeno/metabolismo , Peritonitis/tratamiento farmacológico , Peritonitis/metabolismo , Peritonitis/inducido químicamente , Ácido Úrico/metabolismo , Inflamasomas/metabolismo , Ratones , Interleucina-1beta/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones Endogámicos C57BL , Caspasa 1/metabolismo , Masculino , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Lipopolisacáridos , Piroptosis/efectos de los fármacos , Proteínas Portadoras , Tiorredoxinas
3.
Molecules ; 25(21)2020 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-33158257

RESUMEN

Hyperuricemia is defined as a disease with high uric acid (UA) levels in the blood and a strong risk factor for gout. Urolithin A (UroA) is a main microbial metabolite derived from ellagic acid (EA), which occurs in strawberries and pomegranates. In this study, we evaluated antihyperuricemic effect of UroA in both cultured hepatocytes and hyperuricemic model mice. In cultured hepatocytes, UroA significantly and dose-dependently reduced UA production. In model mice with purine bodies-induced hyperuricemia, oral administration of UroA significantly inhibited the increase in plasma UA levels and hepatic xanthine oxidase (XO) activity. In addition, DNA microarray results exhibited that UroA, as well as allopurinol, a strong XO inhibitor, induced downregulation of the expression of genes associated with hepatic purine metabolism. Thus, hypouricemic effect of UroA could be, at least partly, attributed to inhibition of purine metabolism and UA production by suppressing XO activity in the liver. These results indicate UroA possesses a potent antihyperuricemic effect and it could be a potential candidate for a molecule capable of preventing and improving hyperuricemia and gout.


Asunto(s)
Cumarinas/farmacología , Supresores de la Gota/farmacología , Hepatocitos/metabolismo , Hiperuricemia , Hígado/metabolismo , Ácido Úrico/metabolismo , Animales , Línea Celular , Modelos Animales de Enfermedad , Hiperuricemia/sangre , Hiperuricemia/tratamiento farmacológico , Masculino , Ratones , Ratones Endogámicos ICR
4.
Biosci Biotechnol Biochem ; 81(10): 1956-1966, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28812425

RESUMEN

Nasunin is a major anthocyanin in eggplant peel. The purpose of this study was to examine the anti-inflammatory effects of nasunin in lipopolysaccharide (LPS)-stimulated RAW264 macrophages and to identify the molecular mechanisms underlying these effects. We found that nasunin reduced the LPS-induced secretion of tumor necrosis factor-α, interleukin-6 and nitric oxide, and expression of inducible nitric oxide synthase in a dose-dependent manner. Nasunin diminished LPS-induced nuclear factor-κB (NF-κB) activation by suppressing the degradation of inhibitor of κB-α and nuclear translocation of p65 subunit of NF-κB. Nasunin also attenuated the phosphorylation of Akt and p38, signaling molecules involved in pro-inflammatory mediator production. Moreover, nasunin inhibited the intracellular accumulation of ROS, leading to the suppression of NF-κB activation, Akt and p38 phosphorylation, and subsequent pro-inflammatory mediator production. These findings suggest that nasunin exerts an anti-inflammatory effect and this effect is mediated, at least in part, by its antioxidant activity.


Asunto(s)
Antocianinas/farmacología , Mediadores de Inflamación/metabolismo , Lipopolisacáridos/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Macrófagos/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Animales , Activación Enzimática/efectos de los fármacos , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Lipopolisacáridos/antagonistas & inhibidores , Macrófagos/citología , Macrófagos/metabolismo , Ratones , FN-kappa B/metabolismo , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa de Tipo II/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Células RAW 264.7 , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
5.
Genes Cells ; 19(4): 273-86, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24495227

RESUMEN

Ribosome biogenesis is an essential process for cell growth and proliferation and is enhanced in cancer and embryonic stem cells. Mouse Ly-1 antibody reactive clone product (Lyar) is expressed at very high levels in many tumor, leukemia or embryonic stem cells; is a novel nucleolar protein with zinc-finger DNA-binding motifs and is involved in cell growth regulation. However, cellular function of Lyar remains unexplored. Here, we show that human homologue of Lyar (LYAR) accelerates ribosome biogenesis at the level of processing of preribosomal RNA (pre-rRNA). We show that LYAR is excluded from the nucleolus after actinomycin D treatment and is present in preribosomal fraction of the nuclear extract as well as in the fractions with 40S, 60S and 90S sedimentation coefficients. LYAR is required for processing of 47S/45S, 32S, 30S and 21S pre-rRNAs. In addition, we show that over-expression of LYAR increases cell proliferation without affecting the expression of c-Myc or p53. Combined, these results suggest that some rapidly growing cells enhance ribosome biogenesis by increasing the expression of LYAR.


Asunto(s)
Proteínas de Unión al ADN/metabolismo , Proteínas Nucleares/metabolismo , Precursores del ARN/metabolismo , ARN Ribosómico/metabolismo , Animales , Proliferación Celular , Proteínas de Unión al ADN/genética , Dactinomicina/farmacología , Células HEK293 , Células HeLa , Humanos , Ratones , Proteínas Nucleares/genética , Inhibidores de la Síntesis del Ácido Nucleico/farmacología , Procesamiento Postranscripcional del ARN , Homología Estructural de Proteína
6.
Mol Cell Proteomics ; 10(8): M110.006148, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21536856

RESUMEN

Ribosome biogenesis starts with transcription of the large ribosomal RNA precursor (47S pre-rRNA), which soon combines with numerous factors to form the 90S pre-ribosome in the nucleolus. Although the subsequent separation of the pre-90S particle into pre-40S and pre-60S particles is critical for the production process of mature small and large ribosomal subunits, its molecular mechanisms remain undetermined. Here, we present evidence that p32, fibrillarin (FBL), and Nop52 play key roles in this separation step. Mass-based analyses combined with immunoblotting showed that p32 associated with 155 proteins including 31 rRNA-processing factors (of which nine were components of small subunit processome, and six were those of RIX1 complex), 13 chromatin remodeling components, and six general transcription factors required for RNA polymerase III-mediated transcription. Of these, a late rRNA-processing factor Nop52 interacted directly with p32. Immunocytochemical analyses demonstrated that p32 colocalized with an early rRNA-processing factor FBL or Nop52 in the nucleolus and Cajal bodies, but was excluded from the nucleolus after actinomycin D treatment. p32 was present in the pre-ribosomal fractions prepared by cell fractionation or separated by ultracentrifugation of the nuclear extract. p32 also associated with pre-rRNAs including 47S/45S and 32S pre-rRNAs. Furthermore, knockdown of p32 with a small interfering RNA slowed the early processing from 47S/45S pre-rRNAs to 18S rRNA and 32S pre-rRNA. Finally, Nop52 was found to compete with FBL for binding to p32 probably in the nucleolus. Given the fact that FBL and Nop52 are associated with pre-ribosome particles distinctly different from each other, we suggest that p32 is a new rRNA maturation factor involved in the remodeling from pre-90S particles to pre-40S and pre-60S particles that requires the exchange of FBL for Nop52.


Asunto(s)
Proteínas Portadoras/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , Proteínas Mitocondriales/metabolismo , Proteínas Nucleares/metabolismo , Ribosomas/metabolismo , Unión Competitiva , Línea Celular , Nucléolo Celular/metabolismo , Cuerpos Enrollados/metabolismo , Humanos , Inmunoprecipitación , Unión Proteica , Mapeo de Interacción de Proteínas , Transporte de Proteínas , Precursores del ARN/metabolismo , Procesamiento Postranscripcional del ARN , Proteínas de Unión al ARN/metabolismo , Fracciones Subcelulares/metabolismo
7.
Anim Sci J ; 94(1): e13804, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36617429

RESUMEN

We investigated VEGF expression in the uterus during the estrous cycle in the golden hamster (Mesocricetus auratus). Reverse transcription polymerase chain reaction of genes expressed in the uterus revealed the presence of at least three different VEGF isoforms (hamster VEGF188, VEGF164, and VEGF120). They were highly homologous to the respective mouse and human isoforms. Furthermore, VEGF164 and VEGF120 were predominantly expressed in the hamster uterus during the estrous cycle. In situ hybridization revealed that VEGF is expressed only in the luminal and glandular epithelium of the endometrium but not in the stromal cells or myometrium. The positive reaction of luminal and glandular epithelial cells on day 4 of the estrous cycle (day 1 = day of ovulation) was a little stronger than that of other days of the cycle. These findings suggest that VEGF molecules are secreted by endometrial epithelial cells and play an important role in the maintenance of blood vessels in the endometrial stroma. These results also suggest that uterine changes, such as edema, observed from day 4 to day 1 of the estrous cycle, are expected to occur primarily through the action of VEGF secreted by the uterine endometrial epithelium in preparation for subsequent embryo implantation.


Asunto(s)
Útero , Factor A de Crecimiento Endotelial Vascular , Cricetinae , Femenino , Humanos , Animales , Ratones , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Mesocricetus , Útero/metabolismo , Factores de Crecimiento Endotelial Vascular/metabolismo , Endometrio/metabolismo , Ciclo Estral , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo
8.
Biosci Biotechnol Biochem ; 74(12): 2490-3, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-21150101

RESUMEN

The anti-diabetic effect of perilla (shiso) tea was evaluated in vivo. When shiso tea was given to model rats that spontaneously developed diabetes mellitus (DM), the development of DM was decelerated. In oral glucose tolerance tests, the disappearance of blood glucose in rats administered shiso tea was reinforced. These results suggest that habitual drinking of shiso tea is effective in preventing the onset of diabetes.


Asunto(s)
Bebidas , Diabetes Mellitus/prevención & control , Conducta de Ingestión de Líquido , Perilla/química , Animales , Peso Corporal/efectos de los fármacos , Diabetes Mellitus/sangre , Diabetes Mellitus/patología , Diabetes Mellitus/fisiopatología , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/patología , Masculino , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Factores de Tiempo
9.
Mol Cell Biol ; 26(13): 5131-45, 2006 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16782897

RESUMEN

We have investigated the possible involvement of the ubiquitin-proteasome system (UPS) in ribosome biogenesis. We find by immunofluorescence that ubiquitin is present within nucleoli and also demonstrate by immunoprecipitation that complexes associated with pre-rRNA processing factors are ubiquitinated. Using short proteasome inhibition treatments, we show by fluorescence microscopy that nucleolar morphology is disrupted for some but not all factors involved in ribosome biogenesis. Interference with proteasome degradation also induces the accumulation of 90S preribosomes, alters the dynamic properties of a number of processing factors, slows the release of mature rRNA from the nucleolus, and leads to the depletion of 18S and 28S rRNAs. Together, these results suggest that the UPS is probably involved at many steps during ribosome biogenesis, including the maturation of the 90S preribosome.


Asunto(s)
Nucléolo Celular/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Precursores del ARN/metabolismo , Ribosomas/metabolismo , Ubiquitina/metabolismo , Línea Celular , Nucléolo Celular/química , Nucléolo Celular/ultraestructura , Humanos , Proteínas Nucleares/metabolismo , Inhibidores de Proteasoma , Precursores del ARN/análisis , Precursores del ARN/genética , ARN Ribosómico 18S/genética , ARN Ribosómico 18S/metabolismo , ARN Ribosómico 28S/genética , ARN Ribosómico 28S/metabolismo , Ribosomas/genética , Transcripción Genética , Ubiquitina/análisis
10.
Biochem J ; 413(3): 505-16, 2008 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-18419580

RESUMEN

Although RecQ5beta is a ssDNA (single-stranded DNA)-stimulated ATPase and an ATP-dependent DNA helicase with strand-annealing activities, its cellular function remains to be explored. In the present paper, we used immunopurification and MS-based analyses to show that human DNA helicase RecQ5beta is associated with at least four RNAP II (RNA polymerase II) subunits. RecQ5beta was also present in complexes immunoprecipitated using three different antibodies against the large subunit of RNAP II, or in complexes immunoprecipitated using an anti-FLAG antibody against either FLAG-RNAP II 33 kDa subunit or FLAG-Pin1. Different regions of the non-helicase domain of the RecQ5beta molecule were associated with hypophosphorylated and hyperphosphorylated forms of the RNAP II large subunit independently of DNA and RNA. RecQ5beta was also found in nuclear chromatin fractions and associated with the coding regions of the LDL (low-density lipoprotein) receptor and beta-actin genes. Knockdown of the RecQ5beta transcript increased the transcription of those genes. The results of the present study suggest that RecQ5beta has suppressive roles in events associated with RNAP II-dependent transcription.


Asunto(s)
ARN Polimerasa II/metabolismo , RecQ Helicasas/metabolismo , Transcripción Genética , Línea Celular , Inmunoprecipitación de Cromatina , Células HeLa , Humanos , Immunoblotting , Inmunohistoquímica , Inmunoprecipitación , Reacción en Cadena de la Polimerasa , Unión Proteica , Estructura Terciaria de Proteína , ARN Polimerasa II/química , RecQ Helicasas/química , RecQ Helicasas/genética , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Ultracentrifugación
11.
J Nutr Sci Vitaminol (Tokyo) ; 54(6): 435-9, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19155580

RESUMEN

The present study investigated the effect of dietary soy protein isolate (SPI) on tumor necrosis factor-alpha (TNF) productivity in peritoneal macrophages from nephritic and hepatoma-bearing rats. Dietary SPI significantly inhibited the elevated production of TNF by lipopolysaccharide-stimulated macrophages in nephritic and hepatoma-bearing rats compared with dietary casein, while it exerted no influence on the TNF productivity in normal rats. Removal of the minor components contained in SPI by ethanol extraction could significantly or partially restore the reduced TNF production caused by SPI in nephritic and hepatoma-bearing rats, respectively. These results suggest that dietary SPI could suppress the enhanced productivity of TNF associated with the progression of nephritis and hepatoma, and some factors existing in the ethanol extract of SPI are suggested to be involved in suppressing TNF productivity by macrophages.


Asunto(s)
Caseínas/farmacología , Glútenes/farmacología , Neoplasias Hepáticas Experimentales/dietoterapia , Macrófagos Peritoneales/efectos de los fármacos , Nefritis/dietoterapia , Proteínas de Soja/farmacología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Animales , Caseínas/uso terapéutico , Glútenes/uso terapéutico , Lipopolisacáridos , Macrófagos Peritoneales/metabolismo , Masculino , Ratas , Ratas Wistar , Proteínas de Soja/uso terapéutico , Glycine max , Triticum , Factor de Necrosis Tumoral alfa/biosíntesis
12.
Eur J Pharmacol ; 833: 411-424, 2018 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-29932926

RESUMEN

Urolithin A, a gut microbial metabolite of ellagic acid, is reported to exert anti-inflammatory effects in vitro and in vivo. However, complete mechanisms underlying the regulation of inflammatory responses by urolithin A remain unclear. This study aimed to evaluate the anti-inflammatory potential of urolithin A and its underlying mechanisms in lipopolysaccharide (LPS)-stimulated RAW264 macrophages. Urolithin A significantly attenuated the pro-inflammatory mediator production in LPS-stimulated RAW264 and mouse peritoneal macrophages. This compound significantly suppressed the LPS-elicited nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) activation. The phosphorylation of Akt and c-Jun N-terminal kinase (JNK) was also inhibited by the treatment with urolithin A. Through experiments using kinase inhibitors, urolithin A abolished the LPS-induced phosphatidylinositol 3-kinase (PI3-K)/Akt/NF-κB and JNK/AP-1 signaling pathways, resulting in suppression of pro-inflammatory mediator production. Furthermore, treatment with this compound significantly reduced the intracellular accumulation of reactive oxygen species, which are known to act as secondary messengers in the activation of redox-sensitive transcription factors NF-κB and AP-1. Urolithin A treatment also diminished the LPS-evoked activation of NADPH oxidase (NOX), which is the main source of reactive oxygen species in activated macrophages. The inhibition of this activity by urolithin A led to the prevention of LPS-elicited NF-κB and AP-1 activation as well as Akt and JNK phosphorylation, resulting in the reduction of pro-inflammatory mediator production. Collectively, these results indicate that urolithin A treatment attenuates pro-inflammatory mediator production by suppressing NOX-derived reactive oxygen species-mediated PI3-K/Akt/NF-κB and JNK/AP-1 signaling pathways in LPS-stimulated macrophages.


Asunto(s)
Antiinflamatorios/farmacología , Cumarinas/farmacología , Inflamación/tratamiento farmacológico , NADPH Oxidasas/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Animales , Antiinflamatorios/uso terapéutico , Cumarinas/uso terapéutico , Inflamación/inmunología , Mediadores de Inflamación/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Lipopolisacáridos/inmunología , Masculino , Ratones , Ratones Endogámicos ICR , Modelos Animales , NADPH Oxidasas/metabolismo , FN-kappa B/metabolismo , Peritoneo/citología , Fosfatidilinositol 3-Quinasa/metabolismo , Fosforilación/efectos de los fármacos , Cultivo Primario de Células , Proteínas Proto-Oncogénicas c-akt/metabolismo , Células RAW 264.7 , Especies Reactivas de Oxígeno/inmunología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/inmunología , Factor de Transcripción AP-1/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
13.
J Immunol Res ; 2018: 7270486, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30402511

RESUMEN

Crohn's disease is one of the systemic autoimmune diseases. It commonly affects the small intestine and colon but may involve any portion of the gastrointestinal tract from the mouth to the anus. The most affected area by Crohn's disease is the distal part of the small intestine, in which the bile acid molecules are most efficiently reabsorbed. Bile acids form mixed micelles together with fatty acids, which function as a transport vehicle to deliver fatty acids to the apical membrane of enterocytes for absorption. Therefore, if the terminal ileum is impaired, bile acid malabsorption may occur, which may cause congenital diarrhoea in Crohn's disease. Similarly, the impairment of the terminal ileum also induces fatty acid malabsorption, which may influence the role of fatty acids in Crohn's disease. In contrast, a recent study reported that multidrug resistance protein 1 (MDR1) regulated effector T-cell function in the ileum from bile acid-driven oxidative stress and MDR1 loss of function in a subset of patients with Crohn's disease. However, the role of consumption of fatty acids in Crohn's disease remains to be fully elucidated. This review is aimed at providing an overview of some recent developments in research of Crohn's disease from comprehensive perspective with a focus on the connection between disease location and behaviour, lipid diets, and bile acid malabsorption.


Asunto(s)
Ácidos y Sales Biliares/metabolismo , Enfermedad de Crohn/metabolismo , Enterocitos/fisiología , Ácidos Grasos/metabolismo , Tracto Gastrointestinal/metabolismo , Metabolismo de los Lípidos , Linfocitos T/fisiología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Animales , Enfermedad de Crohn/genética , Dieta , Tracto Gastrointestinal/patología , Humanos , Estrés Oxidativo
14.
Free Radic Biol Med ; 34(8): 1006-16, 2003 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-12684085

RESUMEN

N-3 polyunsaturated fatty acids (PUFAs) are known to have anti-inflammatory effects. Excess production of nitric oxide (NO) is associated with inflammation. Therefore, we examined the effects of PUFAs on NO production and inducible NO synthase (iNOS) expression by stimulated murine macrophages. One typical n-3 PUFA docosahexaenoic acid (DHA) strongly inhibited NO production and iNOS expression in RAW264 macrophages and mouse peritoneal macrophages in a dose-dependent manner. This inhibition was accompanied by inhibiting the oxidative stress-sensitive transcription factor nuclear factor (NF)-kappaB activation. In stimulated macrophages, intracellular peroxides level was enhanced, but pretreatment of DHA dose-dependently inhibited this enhancement. These results suggest that DHA has an antioxidative effect based on the inhibition of the accumulation of intracellular peroxides, and this inhibition caused the suppression of the activation of NF-kappaB, resulting in the inhibition of NO production and iNOS expression. On the other hand, DHA treatment enhanced the level of intracellular glutathione (GSH), and this enhancement is thought to mediate the activity of DHA because lowering the GSH level by inhibiting GSH biosynthesis reversed the DHA-induced suppression of NO production, NF-kappaB activation, and the accumulation of intracellular peroxides. Our results demonstrate that DHA inhibits NO production in macrophages and this inhibition is, in part, mediated by upregulation of GSH.


Asunto(s)
Ácidos Docosahexaenoicos/farmacología , Interferón gamma/farmacología , Lipopolisacáridos/farmacología , Macrófagos/metabolismo , Óxido Nítrico Sintasa/biosíntesis , Óxido Nítrico/metabolismo , Animales , Sitios de Unión , Western Blotting , Línea Celular , Relación Dosis-Respuesta a Droga , Ácidos Grasos/metabolismo , Glutatión/metabolismo , Inflamación , Interferón gamma/metabolismo , Ratones , Ratones Endogámicos BALB C , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II , Estrés Oxidativo , Peróxidos/metabolismo , Unión Proteica , ARN/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Tiempo , Regulación hacia Arriba
15.
Lipids ; 37(5): 481-6, 2002 May.
Artículo en Inglés | MEDLINE | ID: mdl-12056590

RESUMEN

The effects of dietary stearidonic acid (18:4n-3) on inflammatory mediator release in whole blood and splenocytes was investigated in Balb/c mice, and the effects were compared with those of two other n-3 PUFA: alpha-linolenic acid (18:3n-3) and EPA (20:5n-3). TAG mixtures containing 10% of 18:4n-3, 18:3n-3, or 20:5n-3 as the respective sole n-3 PUFA were enzymatically synthesized. Diets containing synthesized TAG mixtures were fed to Balb/c mice for 3 wk. The release of prostaglandin F2 (PGE2) and tumor necrosis factor (TNF) were measured in whole blood and splenocytes stimulated with lipopolysaccharide. In whole blood, the production of TNF was suppressed by all dietary n-3 PUFA (18:3n-3, 18:4n-3, and 20:5n-3) as compared with the control diet, which contained TAG prepared from safflower oil. PGF2 production was not significantly changed. Differences among the n-3 PUFA (18:3n-3, 18:4n-3, and 20:5n-3) were not observed. In splenocytes, PGE2 production was suppressed by dietary n-3 PUFA, but TNF production was not. GC analysis of plasma and splenocyte FA profiles showed an increase in the levels of 20:4n-3, 20:5n-3, and 22:6n-3 in mice fed the diet containing 18:4n-3.


Asunto(s)
Grasas de la Dieta/farmacología , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Insaturados/farmacología , Mediadores de Inflamación/metabolismo , Ácido alfa-Linolénico/farmacología , Animales , Grasas de la Dieta/análisis , Grasas de la Dieta/sangre , Dinoprostona/análisis , Dinoprostona/sangre , Ingestión de Alimentos/efectos de los fármacos , Ácido Eicosapentaenoico , Ácidos Grasos Omega-3/análisis , Ácidos Grasos Omega-3/sangre , Ácidos Grasos Insaturados/análisis , Ácidos Grasos Insaturados/sangre , Crecimiento/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Tamaño de los Órganos/efectos de los fármacos , Bazo/citología , Bazo/efectos de los fármacos , Bazo/metabolismo , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/biosíntesis , Ácido alfa-Linolénico/análisis , Ácido alfa-Linolénico/sangre
16.
Biosci Biotechnol Biochem ; 71(2): 352-7, 2007 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17284860

RESUMEN

Tumor necrosis factor-alpha (TNF) production by peritoneal macrophages and its dietary modification were investigated by using rats fed on a low-protein diet. The rats were given a 20% casein (control) diet or a 3% casein diet for 21 days, and TNF production was measured in activated macrophages of these animals. TNF production was significantly lower in macrophages from rats fed on the low-protein diet than that in macrophages from rats fed on the control diet. Oral administration of a cabbage extract, a known modulator of TNF production, to the low-protein-diet-fed rats significantly enhanced TNF production by macrophages. Glutamine supplementation to the low-protein diet significantly enhanced TNF production as well as TNF mRNA expression. These results indicate that the 3%-casein-diet-fed rat would be useful as a model for reduced TNF production in protein malnutrition. These results also suggest that glutamine administration restored the reduced TNF production associated with protein malnutrition.


Asunto(s)
Dieta , Glutamina/farmacología , Deficiencia de Proteína/metabolismo , Factores de Necrosis Tumoral/biosíntesis , Aminoácidos/sangre , Animales , Proteínas Sanguíneas/metabolismo , Brassica/química , Células Cultivadas , Fibroblastos/metabolismo , Lípidos/sangre , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/metabolismo , Ratones , Tamaño de los Órganos/efectos de los fármacos , Extractos Vegetales/farmacología , Ratas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
17.
Nutr Cancer ; 43(1): 82-9, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-12467139

RESUMEN

The effect of cabbage extract on the production of tumor necrosis factor and its implication in the antitumor effect were examined in vitro and in vivo. Cabbage extract stimulated the production of tumor necrosis factor by rat spleen cells and showed cytotoxic activity in a rat ascites hepatoma cell line (AH109A) when hepatoma cells were cultured with cabbage-stimulated spleen cells. When the extract was adminstered orally to AH109A-bearing rats in combination with lipopolysaccharide injection, the hepatoma weights were reduced to one-half of the vehicle control. The cytotoxic activity of tumor-infiltrating macrophages was induced by simultaneous treatment with cabbage extract and lipopolysaccharide. These results indicate that cabbage extract contains macrophage-stimulating component(s) and can implement the antitumor effect by stimulating the cytotoxicity of tumor-infiltrating macrophages.


Asunto(s)
Antineoplásicos/metabolismo , Brassica , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas Experimentales/metabolismo , Fitoterapia , Extractos Vegetales/farmacología , Factor de Necrosis Tumoral alfa/biosíntesis , Animales , Carcinoma Hepatocelular/inducido químicamente , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Neoplasias Hepáticas Experimentales/inducido químicamente , Macrófagos/metabolismo , Masculino , Ratas , Bazo/metabolismo , Factores de Tiempo , Células Tumorales Cultivadas/trasplante
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