O Litoral Norte de São Paulo é uma região pouco impactada e com elevada sensibilidade ecológica e que reúne perspectivas de grande crescimento econômico com novas instalações de empresas ligadas à exploração do PRÉ-SAL. O presente estudo tem como objetivo analisar a toxicidade dos sedimentos dos Municípios de Ubatuba e Caraguatatuba com os procedimentos da Avaliação e Identificação da Toxicidade (AIT), somente a fase I, proposto pela USEPA (1991; 2007). O ensaio de toxicidade crônico de desenvolvimento embriolarval do ouriço do mar Lytechinus variegatus. Foi extraída a água intersticial dos sedimentos, coletados em quatro enseadas, pelo método de sucção descrito por Winger & Lasier (1991), sendo dois pontos de coleta na Enseada de Ubatuba - Perequê-Açu e Itaguá, um na Enseada do Flamengo, um na Enseada do Mar Virado e uma na Enseada de Caraguatatuba. A AIT evidenciou como agente causador da toxicidade, de modo geral, os compostos pH dependentes e dos metais. As amostras do Perequê-Açu e de Caraguatatuba apresentaram toxicidade em todas as amostras analisadas, as demais amostras não presentaram nenhuma relação entre a toxicidade e a sazonalidade. / São Paulo north coast is a poor impacted region and with high ecological sensitivity which gathers perspectives of great economic growth with new facilities related to the operation of the Pre-Salt companies. The aim of the present study is to analyze the toxicity of sediments from the municipalities of Ubatuba and Caraguatatuba with the procedures of the Toxicity Identification Evaluation (TIE), only the phase I, proposed by USEPA (1991, 2007). The test of chronic toxicity of embriolarval development of sea urchin Lytechinus variegates. Pore water was extracted from the sediments collected in four bays, by the suction method described by Winger & Lasier (1991), being two collection points in Ubatuba Bay - Perequê-Açu and Itaguá, one in Flamengo Bay, one the Mar Virado Bay and one in Caraguatatuba Bay. The TIE evidenced as a causative agent of toxicity, in general, the compounds of pH dependent and of metals. The samples of Perequê-Açu and Caraguatatuba showed toxicity in all samples, the other samples showed no relationship between toxicity and seasonality.

A técnica de estabilização de solos através da incorporação de agentes cimentantes é uma opção eficaz e amplamente utilizada em obras de engenharia geotécnica. Portanto, são relevantes os estudos que contemplam aspectos ainda não bem compreendidos relativos aos efeitos causados pela adição de agentes cimentantes na porosidade dos materiais obtidos e, por consequência, nas propriedades de desempenho destas misturas. Neste sentido, o presente trabalho pretende contribuir no que tange ao conhecimento da estrutura de poros de solos compactados tratados com cal e cimento e sua relação com o comportamento hidráulico destes materiais. Os solos utilizados têm granulometria arenosa e areno-siltosa. As variáveis de controle envolvidas nas análises são os teores dos agentes de cimentação empregados (cal e cimento), densidades de compactação e tempos de cura (para amostras com cal). Para a caracterização dos sistemas de poros empregou-se porosimetria por intrusão de Mercúrio e, de forma complementar, na quantificação das porosidades globais, microtomografia computadorizada de raios x. Um permeâmetro de parede flexível foi utilizado para as determinações das condutividades hidráulicas das amostras estudadas através de ensaios de carga constante. Para as amostras de matriz arenosa pura, os volumes de intrusão indicaram maior refinamento da rede porosa, sob efeito da cimentação, para as condições mais densas de moldagem. Para as amostras de matriz areno-siltosa, ao se variarem as condições de cimentação, e fixando-se o peso específico aparente seco, os volumes intrudidos indicaram o refinamento dos poros quando da adição de cal ou cimento em comparação à condição não cimentada. Com respeito à análise da influência do tempo de cura para as amostras moldadas com cal, os resultados sugeriram que a adição de cal (aos 7 dias de cura) não causou variação da porosidade, comparada à condição sem cimentação, mas aos 28 dias foi possível perceber o aumento da porosidade global e, com o passar do tempo (180 dias) verificou-se a redução da porosidade. O refinamento dos poros se tornou cada vez mais pronunciado conforme a evolução do tempo. Para a matriz arenosa, foi identificado que a adição de cimento e a variação da porosidade de moldagem não implicaram em mudanças mensuráveis no valor da condutividade hidráulica, quando comparadas às condições com e sem cimento. Para as amostras da matriz areno-siltosa, sob diferentes condições analisadas (adição de cal aos diferentes tempos investigados e adição de cimento), foi evidenciado que o peso específico aparente seco de moldagem causou influência significativa sobre a condutividade hidráulica. Foram obtidos bons ajustes para as correlações condutividade hidráulica versus relação porosidade/teor volumétrico do agente cimentante ao se aplicar a potência de 0,032 sobre o parâmetro teor volumétrico do agente cimentante. As curvas obtidas apresentaram relações distintas e sinalizaram aspectos do comportamento do material: aumento da condutividade hidráulica para 28 dias de cura da cal, em relação a 7 dias; para 180 dias e amostras nas condições menos densas, não ocorreu modificação em relação à idade de 28 dias, mas na condição mais densa o parâmetro investigado tornou-se sensível às modificações promovidas por efeitos do tempo de cura; ainda, para as amostras moldadas com cimento, ocorreu redução mais pronunciada da condutividade hidráulica relacionada às condições mais densas de moldagem. / The soil stabilization technique which incorporates cementing agents is an effective alternative and widely used in geotechnical engineering works. Therefore, research on the aspects not well understood related to the effects caused by the addition of cementing agents on the porosity of the obtained materials and, consequently, on the performance properties of cemented blends, are relevant. In this sense, this study aims to contribute improving the knowledge on the pore structure of compacted soils treated with lime and cement, as well as to the relationship between pore structure and the hydraulic behavior of these materials. The used soils have a sandy and sandy-silty grain size distribution. The studied variables involved in the analysis are: the cement and lime contents; compaction density; and curing time (for samples with lime). To characterize the pore systems it was employed the Mercury intrusion porosimetry test and, additionally, in order to quantify the global porosities, it was used x-ray computed microtomography tests. A flexible wall permeameter was used to determinate the hydraulic conductivity of the samples through constant head tests. For sandy samples, the intrusion volumes indicated a more significant reduction of the porous media, under the effect of the cementation, when compacted in denser conditions. For the sandy-silt samples, it was observed that by maintaining the specific dry unit weight constant and by varying the cementation conditions, the intruded volumes indicated a reduction of the pores after the addition of lime or cement compared to the uncemented samples. With regards to the influence of the curing time for samples treated with lime, the results suggested that the addition of lime after 7 days of curing did not cause variation in porosity, compared to condition without cementing additions; however, after 28 days of curing it was observed a slight increase on the overall porosity and, after 180 days of curing, it was observed a reduction of the porosity. The reduction of the pores became more significant with the curing time. Related to the sandy soil, the results indicated that addition of cement to the soil and variations on the molding porosity did not result in measurable changes in the hydraulic conductivity, when compared the conditions with and without cement. For the sandy-silt samples, which were analyzed under different conditions (addition of lime and different curing times, and addition of cement), it was shown that the specific dry unit weight caused significant influence on the hydraulic conductivity. It was observed a satisfactory correlation between hydraulic conductivity and porosity/cementing agent ratio when the volumetric cementing agent content is to the power of 0,032. The obtained curves showed distinct relationships and indicated the following aspects of the material behaviour: the increasing of the hydraulic conductivity after 28 days of curing of the sample with lime, compared to 7 days of curing; after 180 days of curing and under low compaction conditions, it was observed no changes when compared to the samples tested after 28 days of curing; however, in the densest condition the investigated parameter became dependent on the curing time; moreover, for the samples molded with cement, it was observed a more significant reduction of the hydraulic conductivity related to denser molded conditions.

A indústria mineradora do país sofre constantemente com problemas ambientais devido à qualidade e volume de rejeitos gerados durante o processo de extração do minério. Os volumes gerados demandam grandes áreas para armazenagem e consequentemente obras complexas de contenção dos rejeitos. A engenharia geotécnica busca entender o comportamento mecânico de depósitos destes rejeitos através do uso de ensaios tanto de campo como de laboratório. Para isso utiliza ferramentas e procedimentos consagrados no meio técnico seguindo normas e procedimentos estabelecidos e consagrados mundialmente. No entendimento do comportamento mecânico dos solos argilosos, as análises são desenvolvidas em termos de tensões totais, já para os solos arenosos em termos de tensões efetivas. Todavia, para solos com granulometria intermediária, não se tem um consenso no que se refere à interpretação do comportamento mecânicos a partir de ensaios de campo Este trabalho apresenta resultados de ensaios de DMT e CPTU conduzidos em diferentes velocidades de penetração no intervalo de aproximadamente 1 e 57 mm/s, em depósito de rejeito de mineração, para avaliar tanto a influência da velocidade sobre as medidas do ensaio, quanto a transição das condições de fluxo ao redor do piezocone e durante a expansão da membrana do dilatômetro. Um equipamento simples e de baixo custo foi desenvolvido para monitorar a poropressão no centro da lâmina do DMT e dados são interpretados à luz das condições de drenagem impostas durante a execução do ensaio. Resultados indicam que as leituras e os valores de P0 e P1 são medidas de tensão total e por este motivo influenciadas pela magnitude da poropressão gerada durante a penetração da lâmina. Um novo Fator de Velocidade adimensional “Vt” é proposto para identificar possíveis efeitos de consolidação que ocorrem durante a penetração do piezocone e orientações são dadas para utilização de CPTU e DMT em solos de permeabilidade dentro do intervalo de 10-6 a 10-3 cm/s. / The mining industry of the country constantly suffers from environmental problems due to the quality and volume of waste generated during the mineral extraction process. Volumes generated require large areas for storage and consequently complex works of tailings. The geotechnical engineering seeks to understand the mechanical behavior of deposits of this waste by using assays well as laboratory and field. To this end tools and procedures laid down in the technical means following established rules and procedures consecrated worldwide. In the understanding of the mechanical behavior of clay soils, the analyzes are developed in terms of total stresses and for sandy soils in terms of effective stress. However, in soils with intermediate particle size, there is no consensus concerning the interpretation of the mechanical behavior from field trials. This paper presents the results of DMT and CPTU test conducted at different penetration rates in the range of about 1 to 57 mm / s in mining waste deposit to evaluate both the effect of speed on the measurements of the test, as the transition the flow conditions around the piezocone and during the expansion of the dilatometer membrane. A simple and inexpensive equipment has been developed to monitor the pore pressure in the center of the DMT blade and data are interpreted in the light of the imposed drainage conditions during the test. Results indicate that the readings that the P0 and P1 are total stress measurements and for this reason influenced by the magnitude of pore pressure generated during penetration of DMT blade. A new dimensionless Velocity Factor "Vt" is proposed to identify potential consolidation effects occurring during the penetration of piezocone and guidance is provided for use CPTU and DMT in soil permeability in the range 10-6 to 10-3 cm/s.

Les protéines de la famille Bcl-2 sont des régulateurs-clés de l’apoptose (mort cellulaire), qui agissent en contrôlant la perméabilisation de la membrane mitochondriale externe par un processus encore mal connu. La dérégulation des membres de cette famille est souvent associée à la progression tumorale et à la résistance à la chimiothérapie. Notre projet a cherché à éclaircir le mode d’action de ces protéines en se focalisant sur les déterminants structuraux régissant leur interaction avec les membranes biologiques. Les connaissances glanées ont permis (i) de mieux comprendre les déterminants à l’origine de la divergence évolutive entre membres pro- et anti-apoptotiques de la famille Bcl-2 ; (ii) d’ouvrir la voie à la conception de ‘poropeptides’ conçus sur le modèle des hélices d’insertion membranaire des protéines Bcl-2, et qui pourraient être utilisés pour induire l’apoptose de cellules tumorales ou des cellules endothéliales entourant les tumeurs. / Bcl-2 family proteins, which include pro- and antiapoptotic members, positively or negatively regulate mitochondrial outer membrane permeabilization, i.e. a critical step in apoptosis. Over-expression of pro-survival members is associated with tumor progression and may be responsible for chemotherapy resistance. Detailed understanding of the precise mechanisms by which Bcl-2 family members control apoptosis is therefore of considerable therapeutic interest. The overall aim of our project was to delineate a structure-function relationship of Bcl-2 family proteins with emphasis on their membrane-active domains. This analysis has provided a basis (i) to elucidate the molecular mechanisms by which different Bcl-2 proteins evolved opposite functions ; (i) to develop a new generation of pore-forming peptides targeting the mitochondrial outer membrane that may be used to kill neoplastic or tumor endothelial cells.

Mud volcanoes constitute an important component of petroliferous basins and their understanding is essential for successful exploration and development of hydrocarbon fields. They occur in both extensional and compressive tectonic settings, along with passive and active continental margins. Although extensive research exists on the geochemistry, geomorphology and stratigraphic evolution of these localized fluid flow structures, little is known about their geomechanical characteristics. This research investigates the geomechanics of mud volcanoes from the South Caspian Basin and West Nile Delta. This is achieved by establishing a workflow for geomechanical assessment of mud volcanoes using a P-wave velocity dataset from across the mud volcano within the offshore South Caspian Basin. This objective is developed further with the availability of seismic and wellbore data from around the Giza mud volcano, offshore West Nile Delta. Preliminary results of this study from the South Caspian Basin enable confidence in estimating the realistic magnitudes of elastic rock properties, stresses and fluid pressures from empirical and analytical correlations. Moreover, analysis of the variations in fluid pressures allow the fluid flow models around the mud volcano to be constrained and their gradients provide preliminary estimates of the drilling window. Structural and stratigraphic analysis around the Giza mud volcano offers insight into the formation of the mud volcano during the Quaternary and how the fault networks on the hanging wall of the arcuate tectonic fault have acted as conduits for primarily the pre-Pliocene fluids exploiting the areas of weakness along the hanging wall of the fault by entraining the Pliocene sediments. Fluid pressure evaluation reveals small overpressures caused by disequilibrium compaction. Further analysis offers insight into the critical fluid pressures that control fault movement, the stresses responsible for rock deformation around the wellbore and the width of the drilling window constrained by the fracturing of the strata. Analysis presented here provides details on the geomechanical significance of mud volcano environments, with implications for engineering practices. Overall, findings contribute to a systematic understanding of mud volcano settings not only from a field exploration and development point of view, but also at a wider scale for basin analysis and relatively small scale for play analysis.

The tightly regulated openings of the cardiac ryanodine receptor (RyR2) help to ensure that intracellular Ca2+- release from the sarcoplasmic reticulum (SR) can only occur when heart contractions are required. Usually this process is self-regulatory, where Ca2+ both activates and inhibits release of further Ca2+ from the SR. In the progression of heart failure some of this control is lost and in rest periods Ca2+ can leak from the SR into the cytosol. Recent evidence has suggested that Zn2+- dyshomeostasis may contribute to SR Ca2+- leak but the underlying mechanism is unclear. Using single channel electrophysiological studies in combination with live cell imaging of HEK 293 and fibroblasts, this study reveals that Zn2+, along with Ca2+ and the inhibitor Mg2+, plays a physiological role in the grading of Ca2+- release via RyR2. Importantly the data reveal that pathophysiological concentrations of Zn2+ (> 100pM) within the cytosol remove the requirement of Ca2+ to activate RyR2, resulting in irregular channel activity even in the presence of Mg2+. This increase in channel open probability due to Zn2+ is known to be associated with increased Ca2+- release events such as Ca2+ sparks suggesting that Zn2+ is a regulator of the SR Ca2+-leak current. A potential source of releasable Zn2+, which could modulate RyR2 activity in cardiomyocytes, are the acidic organelles (endosomes and lysosomes). This study provides key evidence that the two pore channels (TPCs), which are expressed on the surface of these organelles, are candidate channels for ligand-gated release of Zn2+. Importantly this research demonstrates that dysregulated Zn2+ homeostasis, resulting in elevated Zn2+ within the lysosome, has severe consequences upon cellular Ca2+- release from fibroblasts, which is primarily the result of Zn2+ acting as a pore blocker of TPC2. Together these data reveal a key role of Zn2+ as a second messenger which can regulate intracellular Ca2+- release in both health and disease.

Submitted by Cássia Santos (cassia.bcufg@gmail.com) on 2017-01-30T10:00:16Z No. of bitstreams: 2 Dissertação - Victor Scartezini Terra - 2016.pdf: 3940729 bytes, checksum: 27241c105d696ce18e125b5eb6c44691 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-01-30T10:04:56Z (GMT) No. of bitstreams: 2 Dissertação - Victor Scartezini Terra - 2016.pdf: 3940729 bytes, checksum: 27241c105d696ce18e125b5eb6c44691 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-01-30T10:04:56Z (GMT). No. of bitstreams: 2 Dissertação - Victor Scartezini Terra - 2016.pdf: 3940729 bytes, checksum: 27241c105d696ce18e125b5eb6c44691 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2016-08-29 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Natural disasters related to landslides have caused thousands of deaths and left tens of thousands homeless people around the world. Landslides can occur in most cases due to factors related to water infiltration on soil, causing a raise in the positive pore-water pressure. But what is often observed is that both water infiltration and the reduction of negative pore-water pressure due to water infiltration are not, in practice, enough to justify some of the observed landslides. Some less conventionals mechanisms, such as lightning, are not, usually, taken in consideration in a failure analysis, but can contribute to the factor of safety reduction. This paper aims to study the effects of atmospheric discharges in the stability of natural slopes of residual soils. Partial differential equations governing the coupled flow of pore-water and pore-air are developped. The numerical modeling is made with the FlexPDE software, version 6. The results show that there is a raise on pore-air pressure inside the soil due to atmospheric discharge. However, the raise of pore-air pressure works both in the raise of the apparent cohesion and the reduction on net pressure. It is concluded that any failure due to atmospheric discharge will present a shallow slip surface. / Desastres naturais relacionados a deslizamentos de massas de terra já causaram milhares de mortes e dezenas de milhares de desabrigados no mundo inteiro. Os deslizamentos podem ocorrer em sua maioria devido aos fatores provenientes da infiltração de água no solo, gerando aumento das poropressões positivas de água. Mas o que se observa frequentemente, é que a infiltração e a redução das poropressões negativas muitas vezes não são, na prática, o suficiente para justificar todos os escorregamentos observados. Mecanismos menos convencionais como descargas atmosféricas e o aumento das poropressões de ar consequentes do efeito Lisse normalmente não são levados em consideração em análises de ruptura, mas podem contribuir para a diminuição do fator de segurança de taludes. Esta pesquisa tem como objetivos, portanto, estudar como os efeitos do avanço da frente de infiltração e das descargas atmosféricas irão afetar a estabilidade de taludes em encostas naturais de solos residuais. Além disso, cita-se como objetivos secundários o desenvolvimento de modelos numéricos para análises acopladas de fluxo de água e ar, e a verificação desses modelos por meio de análises de validação. Um estudo detalhado de como a onda de choque e os gradientes de temperatura de descargas atmosféricas se comportam ao atingir a superfície terrestre é desenvolvido para que se possam definir as condições de fronteira do problema. Equações diferenciais parciais acopladas para fluxo de água e ar são desenvolvidas. As análises são feitas com o auxílio do programa FlexPDE, versão 6. Os resultados mostraram que há um aumento das poropressões de ar na massa de solo provenientes de descargas atmosféricas ou do efeito Lisse. No entanto, tais acréscimos de poropressão de ar trabalham tanto a favor do ganho de coesão aparente como como na diminuição das tensões líquidas. No estudo da influência do aumento das poropressões de ar como consequência de descargas atmosféricas conclui-se que eventuais rupturas de taludes causadas por isso serão rasas. Com relação ao estudo do aumento de poropressão de ar em taludes como consequência do efeito Lisse, conclui-se que os acréscimos de poropressão de ar serão maiores na massa de solo quando mais próximo da saturação estiver o solo.

O Litoral Norte de São Paulo é uma região pouco impactada e com elevada sensibilidade ecológica e que reúne perspectivas de grande crescimento econômico com novas instalações de empresas ligadas à exploração do PRÉ-SAL. O presente estudo tem como objetivo analisar a toxicidade dos sedimentos dos Municípios de Ubatuba e Caraguatatuba com os procedimentos da Avaliação e Identificação da Toxicidade (AIT), somente a fase I, proposto pela USEPA (1991; 2007). O ensaio de toxicidade crônico de desenvolvimento embriolarval do ouriço do mar Lytechinus variegatus. Foi extraída a água intersticial dos sedimentos, coletados em quatro enseadas, pelo método de sucção descrito por Winger & Lasier (1991), sendo dois pontos de coleta na Enseada de Ubatuba - Perequê-Açu e Itaguá, um na Enseada do Flamengo, um na Enseada do Mar Virado e uma na Enseada de Caraguatatuba. A AIT evidenciou como agente causador da toxicidade, de modo geral, os compostos pH dependentes e dos metais. As amostras do Perequê-Açu e de Caraguatatuba apresentaram toxicidade em todas as amostras analisadas, as demais amostras não presentaram nenhuma relação entre a toxicidade e a sazonalidade. / São Paulo north coast is a poor impacted region and with high ecological sensitivity which gathers perspectives of great economic growth with new facilities related to the operation of the Pre-Salt companies. The aim of the present study is to analyze the toxicity of sediments from the municipalities of Ubatuba and Caraguatatuba with the procedures of the Toxicity Identification Evaluation (TIE), only the phase I, proposed by USEPA (1991, 2007). The test of chronic toxicity of embriolarval development of sea urchin Lytechinus variegates. Pore water was extracted from the sediments collected in four bays, by the suction method described by Winger & Lasier (1991), being two collection points in Ubatuba Bay - Perequê-Açu and Itaguá, one in Flamengo Bay, one the Mar Virado Bay and one in Caraguatatuba Bay. The TIE evidenced as a causative agent of toxicity, in general, the compounds of pH dependent and of metals. The samples of Perequê-Açu and Caraguatatuba showed toxicity in all samples, the other samples showed no relationship between toxicity and seasonality.

The understanding of multiphase flow properties is essential for the exploitation of hydrocarbon reserves in a reservoir; these properties in turn are dependent on the geometric properties and connectivity of the pore space. The determination of the pore size distribution in carbonate reservoirs remains challenging; carbonates exhibit complex pore structures comprising length scales from nanometers to several centimeters. A major challenge to the accurate evaluation of these reservoirs is accounting for pore scale heterogeneity on multiple scales. This is the topic of this thesis. Conventionally, this micron scale information is achieved either by building stochastic models using 2D images or by combining log and laboratory data to classify pore types and their behaviour. None of these capture the true 3D connectivity vital for flow characterisation. We present here an approach to build realistic 3D network models across a range of scales to improve property estimation through employment of X-ray micro-Computed Tomography (μCT) and Focussed Ion Beam Tomography (FIBT). The submicron, or microporous, regions are delineated through a differential imaging technique undertaken on x-ray CT providing a qualitative description of microporosity. Various 3-Phase segmentation methods are then applied for quantitative characterisation of those regions utilising the attenuation coefficient values from the 3D tomographic images. X-ray micro-CT is resolution limited and can not resolve the detailed geometrical features of the submicron pores. FIB tomography is used to image the 3D pore structure of submicron pores down to a scale of tens of nanometers. We describe the experimental development and subsequent image processing including issues and difficulties resolved at various stages. The developed methodology is implemented on cores from producing wackstone and grainstone reservoirs. Pore network models are generated to characterise the 3D interconnectivity of pores. We perform the simulations of petrophysical properties (permeability and formation resistivity) directly on the submicron scale image data. Simulated drainage capillary pressure curves are matched with the experimental data. We also present some preliminary results for the integration of multiscale pore information to build dual-scale network models. The integration of multiscale data allows one to select appropriate effective medium theories to incorporate sub-micron structure into property calculations at macro scale giving a more realistic estimation of properties.

Le monoxyde d'azote (NO) est formé à partir de L-arginine par la famille des NO synthases. La dysrégulation de la synthèse de cette molécule de signalisation cellulaire est impliquée dans le développement d'un grand nombre de pathologies. Les effets cellulaires du NO sont en partie dus à une inhibition des complexes de la chaîne respiratoire mitochondriale. Nous nous sommes intéressés aux effets du NO sur la régulation de l'oxydation phosphorylante et de le transition de perméabilité, deux processus mitochondriaux gouvernant la survie cellulaire. Nous avons ainsi démontré que l'inhibition de la cytochrome c oxydase (COX) par le NO était associée à une inhibition de la respiration et de la synthèse d'ATP. Cependant le NO augmente l'efficacité de l'oxydation phosphorylante (ATP/O) en diminuant le processus de « slipping ». Toutefois, notre travail a mis en exergue un effet du NO dépendant du substrat utilisé. En présence de NADH seul, le NO n'a pas l'effet bénéfique sur le rendement de l'oxydation phosphorylante, obtenu avec le FADH2 seul ou associé au NADH. L'étude de l'état d'oxydoréduction des cytochromes de la COX a révélé que dans les mitochondries énergisées avec du FADH2 seul ou en association avec le NADH, les cytochromes aa3 sont plus réduits qu'en présence de NADH seul. Nous pouvons suggérer que le « slipping » au niveau de la COX soit dépendant de l'état d'oxydoréduction de ses cytochromes. Le NO pourrait donc être un régulateur physiologique du processus d'oxydation phosphorylante. Nous avons également cherché à étayer l'hypothèse selon laquelle l'inhibition du complexe I aurait un effet anti-apoptotique en inhibant l'ouverture du PTP et la libération de cytochrome c. Le NO ayant un effet sur la chaîne respiratoire dans sa globalité, nous n'avons pu certifier que son effet activateur sur l'ouverture du pore soit dû à l'inhibition d'un complexe en particulier. Il semble que le phénomène de transition de perméabilité soit sensible à l'inhibition du complexe II. L'inhibition du complexe II par un inhibiteur comme le TTFA ou le malonate aurait un effet pro-apoptotique et ce malgré la présence d'inhibiteurs puissants du PTP comme la ciclosporine. Ces résultats suggèrent que le complexe II ferait partie des complexes protéiques régulateurs du PTP et que son inhibition soit dominante sur l'effet induit par l'inhibition du complexe I.