RESUMEN
Periodontitis is a chronic inflammatory and immune reactive disease induced by the subgingival biofilm. The therapeutic effect for susceptible patients is often unsatisfactory due to excessive inflammatory response and oxidative stress. Sinensetin (Sin) is a nature polymethoxylated flavonoid with anti-inflammatory and antioxidant activities. Our study aimed to explore the beneficial effect of Sin on periodontitis and the specific molecular mechanisms. We found that Sin attenuated oxidative stress and inflammatory levels of periodontal ligament cells (PDLCs) under inflammatory conditions. Administered Sin to rats with ligation-induced periodontitis models exhibited a protective effect against periodontitis in vivo. By molecular docking, we identified Bach1 as a strong binding target of Sin, and this binding was further verified by cellular thermal displacement assay and immunofluorescence assays. Chromatin immunoprecipitation-quantitative polymerase chain reaction results also revealed that Sin obstructed the binding of Bach1 to the HMOX1 promoter, subsequently upregulating the expression of the key antioxidant factor HO-1. Further functional experiments with Bach1 knocked down and overexpressed verified Bach1 as a key target for Sin to exert its antioxidant effects. Additionally, we demonstrated that Sin prompted the reduction of Bach1 by potentiating the ubiquitination degradation of Bach1, thereby inducing HO-1 expression and inhibiting oxidative stress. Overall, Sin could be a promising drug candidate for the treatment of periodontitis by targeting binding to Bach1.
Asunto(s)
Factores de Transcripción con Cremalleras de Leucina de Carácter Básico , Flavonoides , Estrés Oxidativo , Periodontitis , Ubiquitinación , Animales , Humanos , Masculino , Ratas , Antioxidantes/farmacología , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/efectos de los fármacos , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Western Blotting , Inmunoprecipitación de Cromatina , Modelos Animales de Enfermedad , Simulación del Acoplamiento Molecular , Estrés Oxidativo/efectos de los fármacos , Ligamento Periodontal/efectos de los fármacos , Ligamento Periodontal/metabolismo , Ligamento Periodontal/citología , Periodontitis/tratamiento farmacológico , Periodontitis/prevención & control , Periodontitis/metabolismo , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Ubiquitinación/efectos de los fármacos , Flavonoides/farmacologíaRESUMEN
BACKGROUND: Uvaria chamae (UC) and Olax subscorpioidea (OS) roots are included in traditional anti-cancer remedies and some studies have identified their chemopreventive/chemotherapeutic potential. This study aimed to identify some cellular/molecular mechanisms underlying such potential and the associated chemical constituents. METHODS: Effect on the viability of cancer cells was assessed using the Alamar Blue assay; ability to modulate oxidative stress was assessed using the 2',7'-dichlorofluorescein diacetate (DCFDA) assay; potential to modulate Nuclear factor erythroid 2-related factor like-2 (Nrf2) activity was assessed in the AREc32 luciferase reporter cell line; and anti-inflammatory effect was assessed using lipopolysaccharide-induced nitric oxide release model in the RAW264.7 cells (Griess Assay). Chemical constituents were identified through liquid chromatography-mass spectrometry (LC-MS). RESULTS: Extracts up to 100 µg/ml were non-toxic or mildly toxic to HeLa, AREc32, PC3 and A549 cells (IC50 > 200 µg/ml). Each extract reduced basal and peroxide-induced levels of reactive oxygen species (ROS) in HeLa cells. OS and UC activated Nrf2, with UC producing nearly four-fold induction. Both extracts demonstrated anti-inflammatory effects. Chamanetin, isochamanetin, isouvaretin, uvaricin I and other compounds were found in U. chamae root extract. CONCLUSION: As Nrf-2 induction, antioxidant and anti-inflammatory activities are closely linked with chemoprevention and chemotherapy of cancers, the roles of these plants in traditional anti-cancer remedies are further highlighted, as is their potential as sources of drug leads.
Asunto(s)
Antineoplásicos/farmacología , Doxorrubicina/farmacología , Neoplasias/tratamiento farmacológico , Olacaceae/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Uvaria/química , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antineoplásicos/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas/efectos de los fármacos , Doxorrubicina/uso terapéutico , Humanos , Extractos Vegetales/química , Raíces de Plantas/química , Plantas Medicinales/química , Streptomyces/químicaRESUMEN
Gene silencing in S. pombe occurs by heterochromatin formation at the centromere (cen), mating-type (mat) and telomere loci. It is mediated by silencing factors including Swi6, Clr1-4, Rhp6 and Pola. RNAi pathway also plays a role in establishment of silencing at the mat and cen loci. Recently, the stress response factors, Atf1 and Pcr1were shown to play an RNAi-independent role in silencing at the mat3 locus through a cis-acting Atf1-binding site located within the repression element REIII and recruitment of the silencing factors Clr3 and Clr6. Another cis-acting site, named repression element REII abutting the mat2 locus, also establishes heterochromatin structure through Clr5 and histone deacetylases but independently of H3-Lys9-methylation and RNAi. Here, we report the occurrence of binding sites for another oxidative response factor, the pombe AP1- like factor Pap1, at the mating-type, centromere and telomere loci. By genetic studies we show that these sites play a role in silencing at the outer repeats of centromeres as well as mating-type locus and this effect is mediated through Pap1 binding site and interaction with and recruitment of the HP1/Swi6. Importantly, pap1Δ cells display a silencing defect even in absence of the oxidative stress. Such a role of Pap1 in heterochromatin formation may be evolutionarily conserved.
Asunto(s)
Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/fisiología , Centrómero , Interferencia de ARN/fisiología , Proteínas Represoras/fisiología , Proteínas de Schizosaccharomyces pombe/fisiología , Schizosaccharomyces/fisiología , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/efectos de los fármacos , Inhibidores de Histona Desacetilasas/farmacología , Ácidos Hidroxámicos/farmacología , Estrés Oxidativo , Schizosaccharomyces/genética , Schizosaccharomyces/metabolismo , Proteínas de Schizosaccharomyces pombe/efectos de los fármacosRESUMEN
The Arabidopsis thaliana R2R3-MYB transcription factor AtMYB32 and its homologs AtMYB4 and AtMYB7 play crucial roles in the regulation of phenylpropanoid metabolism. In addition, AtMYB4 and AtMYB7 are involved in the response to abiotic stress. However, the function of AtMYB32 remains unclear. In this study, we found that AtMYB32 is induced by abscisic acid (ABA) and repressed by drought stress. AtMYB32 positively regulates ABA-mediated seed germination and early seedling development. The expression of ABSCISIC ACID-INSENSITIVE 3 (ABI3), ABI4 and ABI5, which encode key positive regulators of ABA signaling, was upregulated in response to ABA in AtMYB32-overexpressing plants and downregulated in the atmyb32-1 mutant. In addition, we found that the atmyb32-1 mutant was drought resistant. Consistent with the drought-resistant phenotype, the transcript levels of C-repeat binding factor 4 (CBF4) were higher in the atmyb32-1 mutant in response to drought stress. Electrophoretic mobility shift assays (EMSAs) and chromatin immunoprecipitation (ChIP) assays revealed that AtMYB32 binds directly to the ABI3, ABI4, ABI5 and CBF4 promoters both in vitro and in vivo. Genetically, ABI4 was found to be epistatic to AtMYB32 for ABA-induced inhibition of seed germination and early seedling development. Taken together, our findings revealed that AtMYB32 regulates the ABA response by directly promoting ABI3, ABI4 and ABI5 expression and that the drought stress response likely occurs because of repression of CBF4 expression.
Asunto(s)
Ácido Abscísico/farmacología , Proteínas de Arabidopsis/metabolismo , Arabidopsis/efectos de los fármacos , Arabidopsis/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Transactivadores/metabolismo , Factores de Transcripción/metabolismo , Proteínas de Arabidopsis/efectos de los fármacos , Proteínas de Arabidopsis/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/efectos de los fármacos , Sequías , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas/genética , Transactivadores/efectos de los fármacos , Factores de Transcripción/efectos de los fármacosRESUMEN
Cerebral ischemia-reperfusion injury is a common complication that occurs during stroke treatment. Increasingly, microRNAs have been found to participate in the modulation of neuron function; however, the role of microRNAs in cerebral ischemia-reperfusion injury remains unclear. We developed a mechanism of cerebral ischemia-reperfusion injury using a cellular model of oxygen-glucose deprivation and reoxygenation-induced injury in human neuroblastoma SH-SY5Y cells. We found that treatment of oxygen-glucose deprivation and reoxygenation promoted the apoptosis of SH-SY5Y cells. Analysis of microRNAs sequencing revealed that the expression of microRNA-27a-5p was induced, and microRNA-29b-3p expression was inhibited in neuroblastoma cells exposed to oxygen-glucose deprivation and reoxygenation. Either inhibition of microRNA-27a-5p or overexpression of microRNA-29b-3p mitigated oxygen-glucose deprivation and reoxygenation-induced cellular apoptosis. Bach1 was authenticated as a target gene of microRNA-27a-5p. Also, microRNA-27a-5p mediated the expression of Bach 1 along with its downstream signaling. N-hydroxy-N'-(4-butyl-2-methylphenyl)-formamidine protected against oxygen-glucose deprivation and reoxygenation-induced apoptosis while decreasing miR-27a-5p expression and increasing microRNA-29b-3p expression. These results suggested that microRNA-27a-5p and microRNA-29b-3p may contribute to oxygen-glucose deprivation and reoxygenation-induced cellular injury. At the same time, N-hydroxy-N'-(4-butyl-2-methylphenyl)-formamidine protects SH-SY5Y cells against oxygen-glucose deprivation and reoxygenation-induced injury partly through the inhibition of microRNA-27-a-5p and promotion of the Bach1/HO-1 signaling pathway.
Asunto(s)
Amidinas/farmacología , Apoptosis , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico , Glucosa/metabolismo , Hipoxia/metabolismo , MicroARNs , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/efectos de los fármacos , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Línea Celular Tumoral , Humanos , MicroARNs/efectos de los fármacos , MicroARNs/metabolismoRESUMEN
OBJECTIVE: The basic leucine zipper transcription factor, ATF-like (BATF), a member of the Activator protein-1 family, promotes transcriptional activation or repression, depending on the interacting partners (JUN-B or C-JUN). Here, we investigated whether the BATF/JUN complex exerts regulatory effects on catabolic and anabolic gene expression in chondrocytes and contributes to the pathogenesis of osteoarthritis (OA). METHODS: Primary cultured mouse chondrocytes were treated with proinflammatory cytokines (interleukin-1ß, IL-6 or tumour necrosis factor-α) or infected with adenoviruses carrying the Batf gene (Ad-Batf). Expression of BATF and JUN was examined in human and mouse experimental OA cartilage samples. Experimental OA in mice was induced by destabilisation of the medial meniscus or intra-articular injection of Ad-Batf. The chromatin immunoprecipitation assay was used to examine the binding of BATF and JUN to the promoter regions of candidate genes. RESULTS: Overexpression of BATF, which forms a heterodimeric complex with JUN-B and C-JUN, induced upregulation of matrix-degrading enzymes and downregulation of cartilage matrix molecules in chondrocytes. BATF expression in mouse joint tissues promoted OA cartilage destruction, and conversely, knockout of Batf in mice suppressed experimental OA. Pharmacological inhibition of BATF/JUN transcriptional activity reduced the expression of matrix-degrading enzymes and protected against experimental OA in mice. CONCLUSIONS: BATF/JUN-B and BATF/C-JUN complexes play important roles in OA cartilage destruction through regulating anabolic and catabolic gene expression in chondrocytes. Our findings collectively support the utility of BATF as a therapeutic target for OA.
Asunto(s)
Artritis Experimental/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Cartílago Articular/metabolismo , Condrocitos/metabolismo , Osteoartritis/genética , Proteínas Proto-Oncogénicas c-jun/genética , Animales , Artritis Experimental/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/efectos de los fármacos , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Cartílago Articular/citología , Cartílago Articular/efectos de los fármacos , Células Cultivadas , Condrocitos/efectos de los fármacos , Citocinas/farmacología , Humanos , Interleucina-1beta/farmacología , Interleucina-6/farmacología , Masculino , Ratones , Ratones Noqueados , Osteoartritis/metabolismo , Proteínas Proto-Oncogénicas c-jun/efectos de los fármacos , Proteínas Proto-Oncogénicas c-jun/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
Our previous studies demonstrated that tetrachlorobenzoquinone (TCBQ), an active metabolite of pentachlorophenol, has effects on the generation of reactive oxygen species (ROS) and oxidative stress in vitro and in vivo. Nuclear factor erythroid-derived 2-like 2 (Nrf2) is a cellular sensor of electrophilic or oxidative stress that regulates the expression of antioxidant enzymes and defensive proteins. We have illustrated that TCBQ activates Nrf2 signaling by promoting the formation of the Kelch-like ECH-associated protein 1 (Keap1) cross-linking dimer and the formation of an ubiquitination switch from Nrf2 to Keap1. The activation of Nrf2 by TCBQ may serve as an adaptive response to a TCBQ-induced oxidative insult. BTB and CNC homolog 1 (Bach1) compete with Nrf2, leading to the negative regulation of the antioxidant response element (ARE). In this report, we propose that TCBQ induces the dynamic inactivation of Bach1. We observed a rapid nuclear efflux of Bach1 and an accumulation of Nrf2 in nuclei upon TCBQ treatment that precedes the binding of Nrf2 with ARE. We found that the nuclear export of Bach1 is dependent on its chromosomal region maintenance 1 (Crm1) interaction and tyrosine phosphorylation. Although TCBQ induces the ubiquitination of Bach1, TCBQ also increases the mRNA and protein levels of Bach1, returning Bach1 to normal levels. Moreover, we found that TCBQ-induced activation of Nrf2 involves c-Jun N-terminal kinase (JNK)-P62 signaling.
Asunto(s)
Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/fisiología , Benzoquinonas/farmacología , Proteínas del Grupo de Complementación de la Anemia de Fanconi/fisiología , Hidrocarburos Clorados/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Factor 2 Relacionado con NF-E2/fisiología , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/efectos de los fármacos , Western Blotting , Cicloheximida/farmacología , Proteínas del Grupo de Complementación de la Anemia de Fanconi/efectos de los fármacos , Células Hep G2 , Humanos , Sistema de Señalización de MAP Quinasas/fisiología , Factor 2 Relacionado con NF-E2/efectos de los fármacos , Proteínas Proto-Oncogénicas c-myc/fisiología , Reacción en Cadena en Tiempo Real de la Polimerasa , UbiquitinaciónRESUMEN
The role of a glucagon/cAMP-dependent protein kinase-inducible coactivator PGC-1α signaling pathway is well characterized in hepatic gluconeogenesis. However, an opposing protein kinase B (PKB)/Akt-inducible corepressor signaling pathway is unknown. A previous report has demonstrated that small heterodimer partner-interacting leucine zipper protein (SMILE) regulates the nuclear receptors and transcriptional factors that control hepatic gluconeogenesis. Here, we show that hepatic SMILE expression was induced by feeding in normal mice but not in db/db and high-fat diet (HFD)-fed mice. Interestingly, SMILE expression was induced by insulin in mouse primary hepatocyte and liver. Hepatic SMILE expression was not altered by refeeding in liver-specific insulin receptor knockout (LIRKO) or PKB ß-deficient (PKBß(-/-)) mice. At the molecular level, SMILE inhibited hepatocyte nuclear factor 4-mediated transcriptional activity via direct competition with PGC-1α. Moreover, ablation of SMILE augmented gluconeogenesis and increased blood glucose levels in mice. Conversely, overexpression of SMILE reduced hepatic gluconeogenic gene expression and ameliorated hyperglycemia and glucose intolerance in db/db and HFD-fed mice. Therefore, SMILE is an insulin-inducible corepressor that suppresses hepatic gluconeogenesis. Small molecules that enhance SMILE expression would have potential for treating hyperglycemia in diabetes.
Asunto(s)
Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Ingestión de Alimentos/genética , Gluconeogénesis/genética , Factor Nuclear 4 del Hepatocito/genética , Hepatocitos/metabolismo , Hígado/metabolismo , Animales , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/efectos de los fármacos , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Western Blotting , Línea Celular , Inmunoprecipitación de Cromatina , Dieta Alta en Grasa , Expresión Génica , Glucagón , Factor Nuclear 4 del Hepatocito/metabolismo , Hepatocitos/efectos de los fármacos , Hipoglucemiantes/farmacología , Insulina/farmacología , Hígado/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos , Ratones Noqueados , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Reacción en Cadena de la Polimerasa , Proteínas Proto-Oncogénicas c-akt/genética , Receptor de Insulina/genética , Factores de Transcripción/genéticaRESUMEN
The polysaccharides from Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou sarcocarp (PWJS) is evaluated for the chemical composition, antioxidant activity and hepatoprotective effect. The characteristics of PWJS were determined by FT-IR spectral and HPLC analysis. The antioxidant activity was investigated using in vitro systems. An in vivo study of PWJS against CCl4 induced liver injury was also conducted. HPLC analysis showed that PWJS is an acidic heteropolysaccharide, rich in glucose (38.59%), arabinose (23.16%), galacturonic acid (17.64%) and galactose (10.44%). PWJS displayed strong antioxidant activity in vitro. In the in vivo study, PWJS treatment lowered the serum levels of ALT and AST in CCl4-intoxicated mice. Additionally, levels of antioxidant enzymes (SOD and CAT) and GSH were elevated in liver damage mice by PWJS intervention, while content of MDA was lessened. Meanwhile, PWJS reverses the suppression of Nrf2 nuclear translocation, and increases the protein expression of HO-1, GSTα and NQO1 in liver damage mice. Hematoxylin-eosin staining showed that the condition of liver damage was mitigated. This study demonstrates that PWJS reverses hepatotoxicity in CCl4-intoxicated mice through the mechanisms of antioxidant activity, as well as an augmentation of the Nrf2 pathway in liver tissue.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Polisacáridos/farmacología , Ziziphus/química , Animales , Antioxidantes/farmacología , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/efectos de los fármacos , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/fisiología , Tetracloruro de Carbono/toxicidad , Cromatografía Líquida de Alta Presión , Femenino , Hígado/efectos de los fármacos , Hígado/patología , Espectroscopía de Resonancia Magnética , Masculino , Ratones , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
AIM: To investigate effects of iron on oxidative stress, heme oxygenase-1 (HMOX1) and hepatitis C viral (HCV) expression in human hepatoma cells stably expressing HCV proteins. METHODS: Effects of iron on oxidative stress, HMOX1, and HCV expression were assessed in CON1 cells. Measurements included mRNA by quantitative reverse transcription-polymerase chain reaction, and protein levels by Western blots. RESULTS: Iron, in the form of ferric nitrilotriacetate, increased oxidative stress and up-regulated HMOX1 gene expression. Iron did not affect mRNA or protein levels of Bach1, a repressor of HMOX1. Silencing the up-regulation of HMOX1 nuclear factor-erythroid 2-related factor 2 (Nrf2) by Nrf2-siRNA decreased FeNTA-mediated up-regulation of HMOX1 mRNA levels. These iron effects were completely blocked by deferoxamine (DFO). Iron also significantly decreased levels of HCV core mRNA and protein by 80%-90%, nonstructural 5A mRNA by 90% and protein by about 50% in the Con1 full length HCV replicon cells, whereas DFO increased them. CONCLUSION: Excess iron up-regulates HMOX1 and down-regulates HCV gene expression in hepatoma cells. This probably mitigates liver injury caused by combined iron overload and HCV infection.
Asunto(s)
Carcinoma Hepatocelular/virología , Hemo-Oxigenasa 1/genética , Hepacivirus/genética , Hepatitis C/enzimología , Hepatitis C/virología , Hierro/farmacología , Neoplasias Hepáticas/virología , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/efectos de los fármacos , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Línea Celular Tumoral , Deferoxamina/farmacología , Proteínas del Grupo de Complementación de la Anemia de Fanconi/efectos de los fármacos , Proteínas del Grupo de Complementación de la Anemia de Fanconi/metabolismo , Compuestos Férricos/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Regulación Viral de la Expresión Génica/efectos de los fármacos , Hemo-Oxigenasa 1/efectos de los fármacos , Hemo-Oxigenasa 1/metabolismo , Hepacivirus/efectos de los fármacos , Hepacivirus/metabolismo , Hepatitis C/genética , Humanos , Factor 2 Relacionado con NF-E2/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Ácido Nitrilotriacético/análogos & derivados , Ácido Nitrilotriacético/metabolismo , Estrés Oxidativo , ARN Mensajero/metabolismo , ARN Interferente Pequeño/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proteínas Virales/metabolismoRESUMEN
Human T-lymphotropic virus type 1 (HTLV-1), the first known human retrovirus, induces various human diseases with a long latency period. The mechanism by which the virus causes diseases is still unknown. Studies indicate that viral replication is important at least for the development of HTLV-1 associated myelopathy, and therefore treatments based on our knowledge of human immunodeficiency virus type-1 (HIV-1) can be utilized to develop potent antiretroviral therapies targeting the replication enzymes reverse transcriptase, protease and integrase as well as the envelope glycoproteins. Furthermore, accessory gene products such as Tax and HBZ may also provide targets for chemotherapy. Treatment targeting these viral proteins may prevent the development of other HTLV-1-related diseases including adult T-cell leukemia, although such treatment may not be useful during the progression of the disease. This review describes the characteristics of HTLV-1 replication enzymes, envelope glycoproteins, and accessory proteins Tax and HBZ, and discusses the status of drug development strategies.
Asunto(s)
Antivirales/farmacología , Infecciones por HTLV-I/tratamiento farmacológico , Infecciones por HTLV-I/virología , Virus Linfotrópico T Tipo 1 Humano/efectos de los fármacos , Animales , Antivirales/uso terapéutico , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/efectos de los fármacos , ADN Polimerasa Dirigida por ADN/química , Productos del Gen tax/efectos de los fármacos , Humanos , Inhibidores de Integrasa/farmacología , Inhibidores de Integrasa/uso terapéutico , Inhibidores de la Síntesis del Ácido Nucleico , Inhibidores de Proteasas/farmacología , Inhibidores de Proteasas/uso terapéutico , Inhibidores de la Transcriptasa Inversa/farmacología , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Proteínas del Envoltorio Viral/efectos de los fármacosRESUMEN
Cancer chemoprevention involves the use of natural or synthetic compounds to reduce the risk of developing cancer. One of the potential strategies for preventing cancer in the human population is to use food-based natural products to induce cytoprotective enzymes, such as NAD(P)H:quinone oxidoreductase 1, glutathione S-transferase, superoxide dismutase, and heme oxygenase-1. The regulatory regions of these inducible genes contain the antioxidant response element (ARE), which is activated upon binding of the nuclear factor E2-related protein 2 (Nrf2) transcription factor protein. Nrf2 has been shown to be essential in the upregulation of these genes in response to oxidative stress and treatment with certain dietary phytochemicals. This review presents the current body of knowledge regarding the molecular mechanisms of Nrf2 regulation, and highlights the need for future investigations into how these mechanisms apply to natural product inducers of cytoprotective enzymes.