RESUMO
Neutral sphingomyelinase-2 (nSMase2) is a ceramide-generating enzyme that has been implicated in growth arrest, apoptosis and exosome secretion. Although previous studies have reported transcriptional upregulation of nSMase2 in response to daunorubicin, through Sp1 and Sp3 transcription factors, the role of the DNA damage pathway in regulating nSMase2 remains unclear. In this study, we show that doxorubicin induces a dose-dependent induction of nSMase2 mRNA and protein with concomitant increases in nSMase activity and ceramide levels. Upregulation of nSMase2 was dependent on ATR, Chk1 and p53, thus placing it downstream of the DNA damage pathway. Moreover, overexpression of p53 was sufficient to transcriptionally induce nSMase2, without the need for DNA damage. DNA-binding mutants as well as acetylation mutants of p53 were unable to induce nSMase2, suggesting a role of nSMase2 in growth arrest. Moreover, knockdown of nSMase2 prevented doxorubicin-induced growth arrest. Finally, p53-induced nSMase2 upregulation appears to occur via a novel transcription start site upstream of exon 3. These results identify nSMase2 as a novel p53 target gene, regulated by the DNA damage pathway to induce cell growth arrest.
Assuntos
Doxorrubicina/farmacologia , Esfingomielina Fosfodiesterase/fisiologia , Proteína Supressora de Tumor p53/fisiologia , Regulação para Cima , Dano ao DNA , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Células MCF-7 , RNA Mensageiro/efeitos dos fármacos , Esfingomielina Fosfodiesterase/genética , Esfingomielina Fosfodiesterase/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
Injuries and infectious diseases show high levels of morbidity at home. It is known that diseases associated with the consumption of contaminated or poorly preserved food, can be significantly reduced if proper hygiene practices are observed. This article analyzes the main risks associated with household food consumption and aims to highlight some of the recommendations that are still widely disregarded. In particular, we highlight the issues concerning the management of food (especially cooking and storage) and water (mineral and tap water), as well as good manufacturing practices that the consumer have to take to avoid food contamination. For this purpose, a detailed information on prevention would provide people with a greater awareness of risk and, therefore, a improved perception to the real dangers.
Assuntos
Culinária , Família , Inocuidade dos Alimentos , Doenças Transmitidas por Alimentos/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Qualidade de Produtos para o Consumidor , Escolaridade , União Europeia , Inocuidade dos Alimentos/métodos , Doenças Transmitidas por Alimentos/microbiologia , Humanos , Itália , Medição de Risco , Fatores de Risco , Fatores de TempoRESUMO
Helicobacter pylori is an organism widespread in humans and sometimes responsible for serious illnesses, such as gastric and duodenal ulcers, MALToma and even gastric cancer. It has been hypothesized that the infection route by H. pylori involves multiple pathways including food-borne transmission, as the microorganism has been detected from foods such as sheep and cow milk. This work reports the results of a survey conducted in order to investigate the presence of H. pylori in raw goat, sheep and cow milk produced in Southern Italy, employing a Nested Polymerase Chain Reaction (Nested-PCR) assay for the detection of the phosphoglucosamine mutase gene (glmM), as screening method followed by conventional bacteriological isolation. Out of the 400 raw milk samples examined, 139 (34.7%) resulted positive for the presence of glmM gene, but no strains were isolated. In this work H. pylori DNA has been firstly detected from 41 (25.6%) raw goat milk samples. The results deserve further investigations on the contamination source/s of the milk samples and on the major impact that it may have on consumers.
