Regensburg, Univ., Diss., 2009.

University, Diss., 2004--Konstanz. / Erscheinungsjahr an der Haupttitelstelle: 2003.

Proefschrift Rijksuniversiteit Groningen. / Met lit.opg. - Met samenvatting in het Nederlands.

The aim of this project was to study ATP binding cassette (ABC) transporters in the human placenta, in particular their regulation and role in trophoblast differentiation and survival. The presence and localisation of four major placental drug transporters, multidrug resistance gene product 1 and 3 (MDR1 and 3)/ABC subfamily B members 1 and 4 (ABCB1 and 4), multidrug resistance associated proteins 1 and 2 (MRP1 and 2)/ABCC1 and 2 and breast cancer resistance protein (BCRP)/ABCG2 was initially studied in term human placenta, cultured primary trophoblast and BeWo and Jar trophoblast-like cell lines. Jar cells were found to be more similar to nondifferentiated cytotrophoblast with respect to their ABC protein expression profile, whereas BeWo cells more closely reflected differentiated syncytiotrophoblast. Treatment of primary term trophoblasts in vitro with cytokines (TNF- or IL-1) decreased expression and activity of apical transporters ABCB1/MDR1 and ABCG2/BCRP. Growth factors, on the other hand, increased BCRP expression and activity, while estradiol stimulated BCRP, MDR1 and MDR3 expression MDR1/3 functional activity. The ability of BCRP/ABCG2 to abrogate the apoptotic effects of TNF- and ceramides was studied in primary trophoblast and BeWo cells using pharmacological and molecular (siRNA) approaches. The results suggest that BCRP/ABCG2 contributes to the resistance of trophoblast cells to cytokine-induced (extrinsic) apoptosis, whereas its effects on apoptosis activated via the intrinsic mitochondrial pathway is minimal. This altered resistance was associated with increased intracellular accumulation of ceramides and reduced ability to maintain phosphatidylserine in the inner leaflet of the plasma membrane. A role for BCRP/ABCG2 in cell protection from differentiation-induced stressors was also demonstrated during the process of cell fusion associated with transient loss of plasma membrane lipid asymmetry. Finally, expression of BCRP/ABCG2 (and 9 other genes) was studied in 50 placentas from normal pregnancy and pregnancies complicated with fetal growth restriction (FGR). A marked reduction of BCRP/ABCG2 and MDR1/ABCB1 expression was observed in FGR placentas, while other transporter genes were unaffected. Collectively these data suggest that BCRP/ABCG2 and probably other ABC transporters may play a hitherto unrecognised survival role in the placenta, conferring a “stress resistance” to trophoblast cells.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The Agriculture Plan of Low Carbon (PLAN ABC) aims at the organization and planning of actions that have been made for the adoption of sustainable production technologies, and aim to meet the greenhouse gas emission reduction commitments greenhouse (GHG) emissions in the country. The purpose of this thesis was to quantify the number of hectares approved by the ABC Plan and correlate them with the values of financing through the ABC program in Brazil, through an analysis of correlations between the regions of Brazil, in January 2010 period to December 2014 (annual data). In a second moment was held new correlations, in which we compared the ABC Plan hectares numbers with funding values provided by Brazil and Banrisul Bank in the same southern region of the country, according to the Ministry of Agriculture, Livestock and Supply (MAP). Thus, compared to other regions of the country for having Pearson correlation coefficients almost perfect. Still, four, Northeast, North, Southeast and South, had a significance level less than 5%, which identifies a significant correlation. Finally, based on the results and conclusions of this dissertation, it is suggested that the design and objectives of this study are carried out again with the updated data, thus adding more values to samples. / O Plano de Agricultura de Baixa Emissão de Carbono (PLANO ABC) tem por finalidade a organização e o planejamento das ações que vêm sendo realizadas para a adoção das tecnologias de produção sustentáveis, com o objetivo de responder aos compromissos de redução de emissão de gases do efeito estufa (GEE) no país. O objetivo dessa dissertação consistiu em analisar quantitativamente os números de hectares aprovados pelo Plano ABC e correlacioná-los com os valores dos financiamentos liberados pelo Programa ABC no Brasil, por meio de uma análise de correlações entre as regiões do Brasil, no período de janeiro de 2010 a dezembro de 2014 (dados anuais). Em um segundo momento, foram realizadas novas correlações, nas quais compararam-se os números de hectares do Plano ABC com os valores de financiamentos disponibilizados pelo Banco do Brasil e Banrisul na mesma Região Sul do país, segundo dados do Ministério da Agricultura, Pecuária e Abastecimento (MAPA). Dessa forma, também foi feita a comparação com as demais regiões do país, por possuir coeficientes de correlação de Pearson quase perfeitos. Ainda, as quatros regiões, Nordeste, Norte, Sudeste e Sul, apresentaram nível de significância inferior a 5%, o que identifica uma correlação significativa. Finalmente, com base nos resultados e conclusões dessa dissertação, sugere-se que o delineamento e objetivos deste estudo sejam realizados novamente com os dados atualizados, assim agregando mais valores a amostras.