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Doctoral Thesis
DOI
10.11606/T.42.2018.tde-16022018-094950
Document
Author
Full name
Juliana Florenzano Martorelli
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2017
Supervisor
Committee
Costa, Soraia Kátia Pereira (President)
Carvalho, Maria Helena Catelli de
Farsky, Sandra Helena Poliselli
Lima, Wothan Tavares de
Pedreira Filho, Walter dos Reis
Title in Portuguese
Papel do receptor TRPA1 na susceptibilidade diferencial a inflamação alérgica pulmonar em camundongos de ambos os gêneros expostos à poluição na fase neonatal.
Keywords in Portuguese
Antioxidantes
Asma
Hormônios sexuais
Poluente
Quinonas
TRPs
Abstract in Portuguese
A exposição de camundongos neonatos ao poluente 1,2-naftoquinona (1,2-NQ) induziu maior suscetibilidade dos machos jovens (mas não fêmeas) à asma. O objetivo deste estudo foi investigar o impacto da 1,2-NQ no pulmão de camundongos jovens machos e fêmeas e averiguar as associações entre os receptores de potencial transitório TRPA1 e a 1,2-NQ. Camundongos machos e fêmeas C57Bl/6 (2-5 g) foram expostos a 1,2-NQ (100 nM). Maior atividade da catalase e expressão (RNAm) do Nrf2 foi observado no pulmão das fêmeas 24 h após a exposição da 1,2-NQ. O estímulo alérgico na puberdade aumentou a atividade da glutationa peroxidase, redutase e S-transferase nas fêmeas que, diferentemente dos machos, não exibiram exacerbação da asma, mas mostraram maior nitração e carbonilação proteica, expressão da eNOS e TRPA1. O antagonismo dos TRPA1 reduziu a eosinofilia pulmonar nos machos e inibiu a [Ca2+]i em cultura de neurônios frente a 1,2-NQ. A ausência susceptibilidade em fêmeas se deve a maior defesa antioxidante e a maturidade pulmonar destas.
Title in English
The involvement of the TRPA1 receptor in the differential gender susceptibility to allergic lung inflammation in mice exposed to ambient pollution during neonatal period.
Keywords in English
Antioxidants
Asthma
Pollutant
Quinones
Sex hormones
TRPs
Abstract in English
The mice exposure to 1,2-naphthoquinone (1,2-NQ), during postnatal period induced increased susceptibility of males (but not females) to asthma. The aim of this study was to investigate the intensity of lung damage to impact of 1,2-NQ on young mice of both sexes, and to investigate the associations between TRPA1 and 1,2-NQ. Male and female C57Bl/6 mice (2-5g) were exposed to 1,2-NQ (100 nM). After 24 h postnatal exposure to 1,2-NQ, only female lungs showed increased catalase activity and Nrf2 mRNA expression. The allergic stimuli at puberty led to increased glutathione peroxidase, reductase and S-transferase activities only in female lung, which, unlike male, did not exhibit exacerbation of asma, but showed increased pulmonary nitration and protein carbonylation, and increased mRNA expression of eNOS and TRPA1. The TRPA1 antagonist reduced eosinophilia in male lung and inhibited the increased [Ca2+]i in dorsal root ganglion neurons culture to 1,2-NQ. The lack of susceptibility in female might be linked to increased antioxidant defenses and the pulmonary maturity.
 
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Release Date
2020-02-16
Publishing Date
2018-02-16
 
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