p53-Dependent and p53-Independent Responses of Cells Challenged by Photosensitization.
Photochem Photobiol
; 95(1): 355-363, 2019 01.
Article
em En
| MEDLINE
| ID: mdl-30240018
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína Supressora de Tumor p53
/
Fármacos Fotossensibilizantes
Limite:
Humans
Idioma:
En
Revista:
Photochem Photobiol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Estados Unidos