Mitochondrial dysfunction mediates neuronal cell response to DMMB photodynamic therapy

Raphael de Ávila Narciso Gomes, Alejandro Marmolejo-Garza, Floris-Jan Haan, Teresa Mitchell García, Tingting Chen, Mario Mauthe, Yollanda E Moreira Franco Parisotto, Mario Minor Murakami, Suely Kazue Nagahashi Marie, Maurício S Baptista, Amalia M Dolga*, Marina Trombetta-Lima*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Photodynamic therapy (PDT) is a process in which a photosensitizer (PS) is exposed to specific wavelengths and generates reactive oxygen species (ROS) which act within nanometers. The low invasive nature and directed cytotoxicity of this approach render it attractive to the treatment of different conditions, including the ones that affect the central nervous system (CNS). The effect of PDT on healthy neurons is one main concern over its use in the CNS, since neuronal-like cells were shown to be particularly sensitive to certain PSs. Among available PSs, 1,9-dimethyl-methylene blue (DMMB) stands out as being resistant to reduction to its inactive leuco form and by being able to produce high levels of singlet‑oxygen. In this study, we aimed to investigate DMMB photodamage mechanisms in the hippocampal cell line HT22. Our results demonstrate that DMMB-PDT decrease in cell viability was linked with an increase in cell death and overall ROS production. Besides, it resulted in a significant increase in mitochondrial ROS production and decreased mitochondria membrane potential. Furthermore, DMMB-PDT significantly increased the presence of acidic autolysosomes, which was accompanied by an increase in ATG1 and ATG8 homologue GaBarap1 expression, and decreased DRAM1 expression. Taken together our results indicated that mitochondrial and autophagic dysfunction underlie DMMB-PDT cytotoxicity in neuronal cells.

Original languageEnglish
Article number119429
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1870
Issue number3
Early online date3-Jan-2023
DOIs
Publication statusPublished - Mar-2023

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