Role of TRPA1 receptors in the distinct susceptibility to lung allergic inflammation in both mice gender exposed to pollutant in neonatal phase

• Grant number: 13/02115-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2013
• End date: March 31, 2016
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Soraia Katia Pereira Costa
• Grantee: Juliana Florenzano Martorelli
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

We have previously shown that early exposure to 1,2-naphthoquinone (1,2-NQ) might sensitizes the oxidative system of male, thus leading to an increase in inflammatory response in male but not in female juvenile mice. By comparison, environmental pollutants and reactive species activate TRPA1 channels, that are expressed in bronchopulmonary C-fibre terminals, thus suggesting that these receptors act as a potential target to air pollutants, such as 1,2-NQ. However, little is known regarding downstream signaling mediated by interaction of 1,2-NQ (or its oxidant products generated) with TRPA1. Whether activation of afferent fibers in the airways occurs by direct or indirect interaction of ROS (formed by pollutants) with TRPA1 channels is unknown. This project aims to investigate: 1) the involvement of TRPA1 (or oxidants products formed) in the exacerbation of allergic pulmonary inflammation in young mice exposed to the pollutant 1,2-NQ during neonatal period (6, 8 and 10 days of life); 2) the intensity of the pulmonary damage to the impact of 1,2-NQ, via balance of the expression (mRNA or protein) and / or activity of antioxidant defenses (Nrf2, SOD, catalase, GPx, GR and GST) and markers of oxidative stress (DHE) and 3) the mobilization of intracellular Ca2+ in neurons isolated from root ganglion dorsal front of 1,2-NQ pollutant. To this end, neonatal mice will be exposed to 1,2-NQ nebulization or its vehicle. During the juvenile phase, these mice will be sensitized and challenged with OVA. The in vivo and in vitro assays (biochemical and functional studies) will be carried out based on previous studies of the group or by other authors. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MARTORELLI, Juliana Florenzano. The involvement of the TRPA1 receptor in the differential gender susceptibility to allergic lung inflammation in mice exposed to ambient pollution during neonatal period.. 2017. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.