p53-Dependent and p53-Independent Responses of Cells Challenged by Photosensitization

Autor(es)

Abrantes, Aline B. de P. ^[1] ; Dias, Gustavo C. ^[1] ; Souza-Pinto, Nadja C. ^[1] ; Baptista, Mauricio S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Quim, Dept Bioquim, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Photochemistry and Photobiology; v. 95, n. 1, p. 355-363, JAN 2019.
• Citações Web of Science: 2

Resumo

The p53 protein exerts fundamental roles in cell responses to a variety of stress stimuli. It has clear roles in controlling cell cycle, triggering apoptosis, activating autophagy and modulating DNA damage response. Little is known about the role of p53 in autophagy-associated cell death, which can be induced by photoactivation of photosensitizers within cells. The photosensitizer 1,9-dimethyl methylene blue (DMMB) within nanomolar concentration regimes has specific intracellular targets (mitochondria and lysosomes), photoinducing a typical scenario of cell death with autophagy. Importantly, in consequence of its subcellular localization, photoactive DMMB induces selective damage to mitochondrial DNA, saving nuclear DNA. By challenging cells having different p53 protein levels, we investigated whether p53 modulates DMMB/light-induced phototoxicity and cell cycle dynamics. Cells lacking p53 activity were slightly more resistant to photoactivated DMMB, which was correlated with a smaller sub-G1 population, indicative of a lower level of apoptosis. DMMB photosensitization seems to induce mostly autophagy-associated cell death and S-phase cell cycle arrest with replication stress. Remarkably, these responses were independent on the p53 status, indicating that p53 is not involved in either process. Despite describing some p53-related responses in cells challenged by photosensitization, our results also provide novel information on the consequences of DMMB phototoxicity. (AU)

• Processo FAPESP: 14/18123-4 - Modulação pela proteína p53 da morte celular autofágica induzida por terapia fotodinâmica
• Beneficiário: Aline Bianca de Paiva Abrantes
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 10/51906-1 - Bioenergética, transporte iônico, balanço redox e metabolismo de DNA em mitocôndrias
• Beneficiário: Alicia Juliana Kowaltowski
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/04372-0 - DNA mitocondrial: mecanismos de manutenção de sua estabilidade e impacto em doenças
• Beneficiário: Nadja Cristhina de Souza Pinto
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 12/50680-5 - Fotossensibilização nas ciências da vida
• Beneficiário: Mauricio da Silva Baptista
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 13/07937-8 - Redoxoma
• Beneficiário: Ohara Augusto
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs