RESUMEN
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent and prevalent nitrosamine procarcinogen found in cigarette smoke. The aim of this work is to study alterations in peroxiredoxin (Prx) expression induced by NNK during carcinogenesis. Characterization of Prx genes from hamster was performed using bioinformatics. V79 cells were induced with different concentrations of NNK (0.1-0.4 mg/mL), and the expression levels of six Prx genes (Prx1-Prx6) were measured by qRT-PCR 24 h following NNK treatment. Prx gene expression was induced by NNK stress, and the highest transcription levels were induced by over 20.42-fold relative to that of the control. NNK induced alterations in Prx expression over the course of lung cancer, which means Prxs may play important roles in ROS detoxification under NNK stress and their functions are complementary.
Asunto(s)
Carcinógenos/toxicidad , Regulación de la Expresión Génica/efectos de los fármacos , Nitrosaminas/toxicidad , Peroxirredoxinas/metabolismo , Animales , Carcinógenos/administración & dosificación , Línea Celular , Supervivencia Celular , Cricetinae , Cricetulus , Relación Dosis-Respuesta a Droga , Nitrosaminas/administración & dosificación , Peroxirredoxinas/genéticaRESUMEN
The Hippo pathway was originally identified and named through screening for mutations in Drosophila, and the core components of the Hippo pathway are highly conserved in mammals. In the Hippo pathway, MST1/2 and LATS1/2 regulate downstream transcription coactivators YAP and TAZ, which mainly interact with TEAD family transcription factors to promote tissue proliferation, self-renewal of normal and cancer stem cells, migration, and carcinogenesis. The Hippo pathway was initially thought to be quite straightforward; however, recent studies have revealed that YAP/TAZ is an integral part and a nexus of a network composed of multiple signaling pathways. Therefore, in this review, we will summarize the latest findings on events upstream and downstream of YAP/TAZ and the ways of regulation of YAP/TAZ. In addition, we also focus on the crosstalk between the Hippo pathway and other tumor-related pathways and discuss their potential as therapeutic targets.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Neoplasias/metabolismo , Factores de Transcripción/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Regulación de la Expresión Génica , Proteínas Hedgehog/metabolismo , Humanos , Hipoxia/metabolismo , Sistema de Señalización de MAP Quinasas , Ácido Mevalónico/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Modelos Biológicos , Neoplasias/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Procesamiento Proteico-Postraduccional , Proteínas Serina-Treonina Quinasas/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Receptores Androgénicos/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores Notch/metabolismo , Transducción de Señal , Proteínas Smad/metabolismo , Factores de Transcripción/genética , Vía de Señalización WntRESUMEN
This study examined the antioxidant responses of Daphnia magna following exposure to different concentrations of the ionic liquid (IL) 1-octyl-3-methylimidazolium bromide and the 50% LC(50) concentrations of methylimidazolium bromide ILs with different alkyl-chain lengths. Activities of antioxidant defense enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase) and levels of the antioxidant glutathione and the lipid peroxidation by-product malondialdehyde were measured using traditional methods or commercial kits. The concentration and the alkyl-chain length of ILs were found to strongly influence the antioxidant system of D. magna following IL exposure, and exposure to higher IL concentrations and to ILs with longer alkyl chains generally increased the enzyme activities and biomarker levels examined. Therefore, the present study suggests that oxidative stress is involved in the mechanism of IL-induced toxicity in D. magna.
Asunto(s)
Antioxidantes/metabolismo , Daphnia/efectos de los fármacos , Daphnia/enzimología , Hidrocarburos Bromados/toxicidad , Líquidos Iónicos/toxicidad , Animales , Boratos/toxicidad , Catalasa/metabolismo , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Glutatión Transferasa/metabolismo , Hidrocarburos Bromados/química , Imidazoles/toxicidad , Líquidos Iónicos/química , Malondialdehído/metabolismo , Superóxido Dismutasa/metabolismo , Pruebas de Toxicidad AgudaRESUMEN
Since Alzheimer's disease (AD) is becoming the prevalent dementia in the whole world, more underlying mechanisms are emerging. Long time has the transcription factor NF-κB been identified to participate in AD pathogenesis, various studies have focused on the causes and effects of AD that are linked to NF-κB. In this review we discuss diverse environmental stimuli including oxidative stress, neuroinflammation and metabolism, involved signaling pathways such as PI3K/AKT, MAPK and AGE/RAGE/GSK-3 and newly found ncRNAs that mediate neuron toxicity or neuron protection through NF-κB activation and the following response associated with the same factors in AD. These may provide future orientation of investigation at transcription level and support efficient treatment to AD by a better understanding of the upstream regulators and downstream effectors of NF-κB.
Asunto(s)
Enfermedad de Alzheimer/metabolismo , FN-kappa B/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Animales , HumanosRESUMEN
Hypoxic regions are common in solid tumors and have an impact on tumor progression and on the therapeutic response. However, the underlying mechanism for hypoxic tumor microenvironment has not been entirely elucidated. Recently, long noncoding RNAs (lncRNAs) are being increasingly recognized to contribute to carcinogenesis through diverse mechanisms. To date, several lncRNAs have been described in hypoxia-associated cancer process, implying a potential role in maintaining cellular homeostasis and enabling an adaptive survival under hypoxic stress conditions. While it has been widely accepted that a complex cellular network of gene products, such as protein and miRNA, take part in hypoxic cancer progression, it remains largely elusive how lncRNAs participate in it. In this review, we introduce an update view of lncRNAs, focusing on hypoxia-related lncRNAs. We hereby summarize the cause and consequence of hypoxia-modulated lncRNAs in cancer as well as their functional mechanisms, highlighting the specific roles of lncRNAs in hypoxia response in cancer.