An efficient PeT based fluorescent probe for mapping mitochondrial oxidative stress produced via the Nox2 pathway.
J Mater Chem B
; 10(13): 2230-2237, 2022 03 30.
Article
em En
| MEDLINE
| ID: mdl-35289831
ABSTRACT
The human innate immune system eliminates invading pathogens through phagocytosis. The first step of this process is activating the nicotinamide adenine dinucleotide phosphate oxidase (Nox2) that utilizes NADPH to produce superoxide anion radicals and other reactive oxygen species (ROS). These ROS then alter the mitochondrial membrane potential and increase peroxide in the mitochondria. The peroxide reacts with myeloperoxidase (MPO) and chloride ions to produce pro-inflammatory oxidant hypochlorous acid (HOCl), which causes oxidative stress leading to cell death. The adverse effects of HOCl are highly associated with cardiovascular disease, neurodegenerative disorders, acute lung injuries, inflammatory diseases, and cancer. Therefore, mapping HOCl in the Nox2 pathway is crucial for an in-depth understanding of the innate immune system. Herein, we developed a unique pentacyclic pyridinium probe, PM-S, that exhibited efficient photoinduced electron transfer (PeT) with HOCl triggered methyl(phenyl)sulfane. PM-S showed several advantages, including better chemical stability, large Stokes shifts (>6258 cm-1), high sensitivity (â¼50 nM) and specificity to mitochondria, compared to its parent pyrylium PY-S derivative. This probe is also efficient in studying the HOCl produced via the Nox2 pathway in HepG2 and HeLa cells. Analysis using a simple microplate reader and FACS analysis with various inhibitors and inducers supported the mechanistic understanding of Nox2, which can offer an advanced platform for monitoring the inflammatory process more efficiently.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácido Hipocloroso
/
Corantes Fluorescentes
Limite:
Humans
Idioma:
En
Revista:
J Mater Chem B
Ano de publicação:
2022
Tipo de documento:
Article