Epigenetic Mechanisms of ATM Activation after Helicobacter pylori Infection

Autor(es)

Santos, Juliana C. ^{[1, 2]} ; Gambeloni, Rafael Z. ^[2] ; Roque, Aline T. ^[2] ; Oeck, Sebastian ^{[3, 4]} ; Ribeiro, Marcelo L. ^[2]

Afiliação do(s) autor(es)

^[1] State Univ Campinas UNICAMP, Womens Hlth Hosp Prof Dr Jose Aristodemo Pinotti, Campinas, SP - Brazil

^[2] Sao Francisco Univ, Med Sch, Clin Pharmacol & Gastroenterol Unit, Av Sao Francisco de Assis 218, BR-12916900 Braganca Paulista, SP - Brazil

^[3] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06510 - USA

^[4] Univ Duisburg Essen, Med Sch, Inst Cell Biol Canc Res, Essen - Germany

• Tipo de documento: Artigo Científico
• Fonte: American Journal of Pathology; v. 188, n. 2, p. 329-335, FEB 2018.
• Citações Web of Science: 1

Resumo

Gastric cancer (GC) is the second Leading cause of cancer-related mortality worldwide. The disease develops from the accumulation of several genetic and epigenetic changes. Among other risk factors, Helicobacter pylori infection is considered the main driving factor of GC development. H. pylori infection increases DNA damage levels and leads to epigenetic dysregulation, which may favor gastric carcinogenesis. An early step in double-strand break repair is the recruitment of ataxia-telangiectasia mutated serine/threonine kinase (ATM) to the damaged site, where it plays a key role in advancing the DNA damage checkpoint process. H. pylori infection has been associated with the introduction of double-strand breaks in epithelial cells, triggering damage signaling and repair response involving ATM. Thus, the current study analyzed the effect of H. pylori infection on the DNA damage response sensor, ATM, in gastric epithelial cells and in biopsy specimens from patients with GC. In this study, we identified that H. pylori infection stimulated DNA damage, and therefore induced ATM in a virulence factor-dependent manner. In addition, we found that H. pylori might activate ATM through histone H3 and H4 hyperacetylation and DNA promoter hypomethylation. Our findings show a mechanism associating ATM signaling induction with H. pylori infection. (AU)

• Processo FAPESP: 14/11862-6 - Avaliação do papel regulatório de genes associados à via Wnt/b-catenina sob os mecanismos de reparo ao DNA modulados por H. pylori
• Beneficiário: Marcelo Lima Ribeiro
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/21710-0 - DETERMINAÇÃO DO PERFIL EPIGENÉTICO RELACIONADO AOS SISTEMAS DE REPARO AO DNA INFLUENCIADOS PELA INFECÇÃO POR H. pylori
• Beneficiário: Juliana Carvalho Santos
• Linha de fomento: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/17768-4 - Avaliação do papel regulatório de b-catenina sob os genes do sistema de reparo ao DNA MMR modulados por H. pylori
• Beneficiário: Aline Tengan Roque
• Linha de fomento: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 15/08775-7 - Avaliação do papel da infecção pôr H. pylori na modulação da expressão de miRNAs associados à via Wnt/b-catenina
• Beneficiário: Rafael Zuppardo Gambeloni
• Linha de fomento: Bolsas no Brasil - Iniciação Científica