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Doctoral Thesis
Full name
Ana Carolina Franco Ferreira
Knowledge Area
Date of Defense
São Paulo, 2007
Seelaender, Marilia Cerqueira Leite (President)
Afeche, Solange Castro
Campa, Ana
Cipolla Neto, Jose
Puschel, Gerhard Paul
Title in Portuguese
Avaliação das alterações causadas pelo câncer sobre a produção de melatonina na glândula pineal.
Keywords in Portuguese
Arilalquilamina N-acetiltransferase
Glândula pineal.
Tumor de Walker 256
Abstract in Portuguese
O objetivo desse trabalho foi estudar os mecanismos que alteram a produção de melatonina na glândula pineal durante o processo de caquexia associada ao câncer e o papel de citocinas neste contexto. Os resultados mostraram um aumento da produção de melatonina no grupo inoculado com o Tumor de Walker 256 (GT) junto com uma maior atividade e expressão gênica da enzima AA-NAT, principal enzima reguladora da síntese de melatonina. O estudo in vitro mostrou que a glândula do GT produziu menos melatonina que a glândula do grupo controle (GC) após estimulação com noradrenalina (NOR). Além disso, o TNF-a foi capaz de modular a síntese de melatonina em cultura, promovendo um efeito estimulatório 2h após o inicio da estimulação com NOR, e um inibitório 4h após essa estimulação. Dessa forma, os resultados indicam que produtos na circulação do rato do GT estão envolvidos na modulação encontrada in vivo e que o TNFa- é um forte candidato a participar dessa modulação promovida pelo estabelecimento da síndrome da caquexia sobre a produção de melatonina na glândula pineal.
Title in English
Evaluation of alterations caused by cancer on melatonina production in the pineal gland.
Keywords in English
Pineal gland.
Walker 256 tumor
Abstract in English
The purpose of this work was to investigate the mechanisms that modify melatonin synthesis in pineal gland during cancer related cachexia and the involvement of cytokines in this context. The results showed an increment of melatonin production in the group inoculated with Walker 256 Tumor (GT) together with a higher activity and gene expression of AA-NAT enzyme, main enzyme that regulates melatonin synthesis. The in vitro study showed that glands from GT produced less melatonin than glands of the control group (GC) after noradrenalin (NOR) stimulation. Besides, TNF-a was capable to modulate melatonin synthesis in pineal gland culture, promoting a stimulatory effect 2 hours after NOR stimulation and an inhibitory effect 4 hours after this stimulation. Therefore, the results indicate that products from tumor bearing rat's circulation are probably involved in the modulation found in vivo and that TNF-a is a strong candidate to participate in cachexia-related modulation of melatonin production in pineal gland.
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