Study of the effects of particulate matter from diesel exhaust air pollution on cellular protection mechanisms: AhR, Nrf2 and cyclines

• Grant number: 23/03881-0
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2023
• End date: July 31, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Mariangela Macchione
• Grantee: Mariangela Macchione
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Daniela Perroni Frias ; Juliana Smelan Wilson ; Thais Mauad ; William Kleber Martins Vieira
• Associated scholarship(s): 23/16165-0 - Generation of A549 Knockout for AhR and siRNA-Nrf2, BP.TT

Abstract

Air pollution is an important public health topic, as it causes irreversible damage to the environment and health. Exposure to particulate matter and/or polycyclic aromatic hydrocarbons (PAHs) found in air pollution reveals associations between DNA damage in airway cells and cancer development. The PAHs activate the aryl hydrocarbon receptor (AhR), which regulates xenobiotic metabolizing enzymes (CYP450), together with erythroid nuclear factor 2 (Nrf2), a transcription factor that acts on the basal activation of antioxidant enzymes. AhR is one of the transcription factors that regulate indirect activation of Nrf2 by reactive oxygen species generated by CYP1A1 and, in addition, it also acts to mediate cell cycle control. Likewise, its activation can influence the interaction between xenobiotic - inducer and cause effects in the cycle. In order to study changes in the cellular mechanism, referring to the production of cytokines and in the architecture of the cellular cytoskeleton, Nrf2 silencing and AhR knockout through CRISPR/Cas9 will be performed. A549 lung adenocarcinoma cells exposed or not to diesel exhaust particulate matter (DEP) will be used. The study groups will be: 1) A549 (control); 2) A549 + DEP; 3) A549 + DEP + CRISPR/Cas9 for AhR; 4) A549 + DEP + silenciated for Nrf2; 5) A549 + silenciated for Nrf2; 6) A549 + CRISPR/Cas9 for AhR . (AU)