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Doctoral Thesis
DOI
10.11606/T.42.2014.tde-14052015-102620
Document
Author
Full name
Pedro Henrique Imenez Silva
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2014
Supervisor
Committee
Reboucas, Nancy Amaral (President)
Abdulkader, Fernando Rodrigues de Moraes
Onuchic, Luiz Fernando
Seguro, Antonio Carlos
Torres, Tatiana Teixeira
Title in Portuguese
Análise comparativa dos efeitos da acidose metabólica e respiratória sobre a isoforma 3 do trocador sódio hidrogênio (NHE3).
Keywords in Portuguese
Ácido-base
Biologia molecular
NHE3
Rim
Transportador iônico
Túbulo proximal
Abstract in Portuguese
O parálogo 3 do trocador Na+/H+ (NHE3) é essencial para a reabsorção de HCO3- nos túbulos proximais renais e sua expressão e função adaptam-se às diferentes condições ácido-base do organismo. O objetivo desta tese foi avaliar quais as diferenças entre os efeitos da acidose metabólica (AM) e respiratória (AR) sobre a regulação do NHE3 e identificar variáveis responsáveis pelas respostas adaptativas observadas. Em células OKP, a AM foi simulada diminuindo a [HCO3-] do meio de cultura e a AR aumentando a pCO2 ambiente por 24 h. Foram observados os efeitos das acidoses sobre o RNAm-Nhe3, a presença da proteína-NHE3 na membrana celular e a atividade promotora do gene do Nhe3. Concluiu-se que o pH extracelular não é a variável físico-química responsável por estimular a expressão do NHE3, contudo é um importante candidato à variável responsável por regular o tráfego da proteína para a membrana. Além disso, a região de -471 a -153 pb em relação ao sítio de início de transcrição do promotor do gene do Nhe3 contém prováveis reguladores positivos que atuam em resposta à AM.
Title in English
Comparative analysis of metabolic and respiratory acidosis effects on the sodium hydrogen exchanger isoform 3 (NHE3).
Keywords in English
Acid-base
Ionic transporter
Kidney
Molecular biology
NHE3
Proximal tubule
Abstract in English
The Na+/H+ exchanger 3 (NHE3) is essential for HCO3- reabsorption in renal proximal tubules and its expression and function must adapt to acid-base conditions. The goal of the presente study was to evaluate whether there are differences between metabolic (MA) and respiratory acidosis (RA) with regard to NHE3 modulation and to identify variables that may trigger these distinct adaptive responses. In OKP cells, MA was achieved by lowering [HCO3-] in the cell culture medium and RA by increasing pCO2 in the incubator chamber for 24 h. The effects of both acidosis on Nhe3 mRNA levels, cell-surface NHE3 expression and promoter activity were evaluated. In summary, it was concluded that low extracellular pH is not the physical-chemical variable that up-regulates NHE3 expression, however, extracellular pH is a candidate for the variable related to the NHE3 displacement to the apical membrane. Moreover, the Nhe3 gene promoter region spanning from -471 to -153 base pairs upstream from the transcriptional start site contains putative enhancers regulated in response to MA.
 
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Release Date
2017-05-13
Publishing Date
2015-05-14
 
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