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

Author(s)

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

Affiliation

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

• Document type: Journal article
• Source: Photochemistry and Photobiology; v. 95, n. 1, p. 355-363, JAN 2019.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 12/50680-5 - Photosensitization in life sciences
• Grantee: Mauricio da Silva Baptista
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 17/04372-0 - Mitochondrial DNA: mechanisms for genome integrity maintenance and impact on disease
• Grantee: Nadja Cristhina de Souza Pinto
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 14/18123-4 - Protein p53 modulation of autophagic cell death induced by photodynamic therapy
• Grantee: Aline Bianca de Paiva Abrantes
• Support type: Scholarships in Brazil - Master
• FAPESP's process: 10/51906-1 - Mitochondrial bioenergetics, ion transport, redox state and DNA metabolism
• Grantee: Alicia Juliana Kowaltowski
• Support type: Research Projects - Thematic Grants