High-performance functional electrode materials are critical for the development of electrochemical energy conversion and storage technologies. Among various advanced materials, three-dimensional (3D) porous structures have attracted extensive interest due to their high surface area and capability for efficient mass transport. Metal-organic frameworks (MOFs) are a novel class of porous coordination polymers constructed with organic linkers connected by inorganic nodes. Their extraordinarily high surface area, permanent pores/channels, good thermal and chemical stabilities have made MOFs one of the most promising materials for various electrochemical applications, including electrocatalysis, supercapacitors, Lithium-ion batteries, chemical sensors, etc. The present dissertation focuses on the investigation of charge transfer mechanism in MOF films so as to establish design rules for future MOF design, and the exploration of MOF-based materials for electrochemical and photoelectrochemical applications. To promote the use of MOF-based materials in electrochemical applications, efficient charge transfer is a necessity. In redox-active MOFs, charge transfer can happen through redox hopping, i.e. site-to-site electron hopping coupled to diffusion of counter ions to balance electroneutrality. While the apparent diffusion coefficient (Dapp) has been employed to describe the overall charge transfer efficiency, independent elucidation of electron and ion diffusion is crucial for providing insights into the mechanism of charge transfer in MOFs. In Chapter 2, we investigated the MOF pore size effect on electron and ion diffusion. Three redox-active ferrocene-doped MOF (Fc-MOF) films with different pore sizes immobilized on conductive substrates were prepared, and electron and ion diffusion coefficients and rate constants were quantified by applying a theoretical model to chronoamperometric responses. Increasing MOF pore size led to an increase in ion diffusion rate constant and a decrease in electron diffusion rate constant. The overall charge transfer rate constant increased when MOF pore size increased, implying the ability of promoting efficient charge transfer through control of MOF pore size. As charge transfer via redox hopping proved to be feasible, Chapter 3 focused on the application of a ruthenium(II)-polypyridyl doped MOF film immobilized on a conductive substrate, UiO-67-Ru@FTO, for solid-state electrochemiluminescence (ECL). In the presence of tripropylamine as a coreactant, UiO-67-Ru@FTO exhibited higher ECL intensity and better reproducibility compared to corresponding solution-based ECL system. Subsequently, UiO-67-Ru@FTO was successfully used for dopamine detection, highlighting the great potential of using MOF-based materials as solid-state ECL detector for practical applications. Covalent-organic frameworks (COFs) are a recently emerging family of crystalline organic polymers constructed with organic building blocks linked by covalent bonds. In addition to advantages including high surface area and high porosity that are similar to MOFs, COFs possess low density due to the constitution of light-weighted elements and excellent stability owing to the robust covalent bonds. Therefore, it is of our interest to investigate the properties and potential applications of COFs. Two-dimensional (2D) COFs are composed of conjugated organic layers stacked via - interactions. Chapter 4 focused on understanding the effects of intraplanar -conjugation and interplanar -stacking on the photophysical properties of a 2D COF, TpBpy. Compared to the two building blocks, TpBpy exhibited a red-shifted emission, due to the - stacking. Density functional theory (DFT) calculations were performed on energies of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO). It was found that the extended structure of the framework resulted in a decrease in the HOMO-LUMO gap. The experimental and computational studies reveal the important influence of intraplanar and interplanar interactions on photophysical properties in 2D COFs. In Chapter 5, we modified the COF TpBpy with nickel(II) and investigated its application as an electrocatalyst for 5-hydroxymethylfufural (HMF) oxidation. Unlike TpBpy characterized in Chapter 4, TpBpy thin films were prepared by an interfacial crystallization strategy. The films were transferred to conductive substrates and then post-synthetically modified by nickel acetate. Similar to redox-active MOFs, the resulting TpBpy-Ni COF film exhibited redox conductivity. TpBpy-Ni showed good catalytic activity for HMF oxidation under basic conditions. This study suggests the great potential of functionalized COFs for electrochemical applications. / Doctor of Philosophy / The increasing demand for clean and efficient energy has triggered a great deal of research interest in developing novel energy conversion and storage technologies. In particular, electrochemical (EC) systems including supercapacitors, Lithium-ion batteries, artificial photosynthetic system, fuel cells, etc. have drawn significant attention. The key component in high-performance EC energy conversion and storage devices is the functional electrode materials. Three-dimensional (3D) porous nanostructures have been widely applied as advanced electrode materials due to their high surface area that enables more liquid/solid interfacial interactions, and pores/channels that allows efficient mass diffusion and transport. Metal-organic frameworks (MOFs), made of organic ligands bridged by inorganic nodes, are a novel kind of porous materials with extraordinarily high surface area and permanent porosity. As a result, there is great potential in developing MOF-based electrode materials for EC applications. As the name itself suggests, EC systems rely on electrochemical reactions that involve transfer of charges (i.e. electrons and ions). Therefore, efficient charge transfer is vital for achieving high performance. While MOFs used for gas separation and storage have been reported, their electrochemical applications are still in early stages. The fundamental understanding of charge transfer in MOFs is in its infancy. As a result, there is an urgent demand for understanding the nature of charge transfer in MOFs. In this dissertation, we investigated the mechanism of charge transfer by independent quantification of electron and ion transfer rate constants. With a better understanding in hand, we also explored two electrochemical applications in MOFs, electrocatalysis and electrogenerated chemiluminescence.

Photovoltaic (PV) technologies are a promising approach to achieve clean, renewable energy production on a global scale. However, the widespread implementation of this technology is limited due to the intricate challenges associated with its complex electrochemical processes. One such challenge is the formation of long-lived charge-separated states (CSSs), a process that directly influences device efficiencies. Viable strategies for increasing CSS lifetimes involve the inhibition of parasitic back-electron transfer pathways. In liquid-junction PVs, electronic recombination is prevented by utilizing redox electrolytes that promote directional electron transfer at the electrode/electrolyte interface, where forward electron transfer (i.e. to the electrode) is favored and the corresponding electronic recombination reaction is impeded. To meet this criterion, researchers seek to employ redox electrolytes that undergo a spin-exchange reaction induced by electron transfer. This event, known as charge transfer-induced spin crossover (CTISC), significantly increases the reorganization energy associated with electronic recombination, producing long-lived CSSs and elevated device efficiency. This dissertation describes a suite of manganese-based redox mediators that exhibit CTISC across a tunable range (1.5 V) of formal potentials (E1/2). These complexes are utilized as redox electrolytes in liquid-junction PVs and result in a two-fold enhancement in the device efficiency relative to other CTISC redox species. Photosensitizer regeneration rates are monitored using transient absorption spectroscopy (TAS) to discern the optimal E1/2 values in this class of complexes while density functional theory is employed to calculate the reorganization energy of each species. By implementing these promising electrolytes into PV devices, scientists and engineers are armed with new tools to increase the accessibility and efficiency of next-generation PVs, thereby transforming past promises into progress. / Doctor of Philosophy / To realize next-generation renewable fuels, scientists must understand how electron transfer at an interface is controlled. This dissertation highlights one method of forming a chemically useful and long-lived charge separated state. The formation of this charge separated state is achieved through an electronic reorganization that occurs at a metal center after electron transfer. Chapters 2, 3, and 4 investigate the synthesis and characterization of new metal species that possess this electronic reorganization process and provide an advanced understanding of how this process facilitates the formation of long-lived charge separated states. This work is intended to motivate new schools of thought that aid the design of next-generation catalytic materials for light-driven chemical reactions.

In 1998, the Virginia Department of Transportation (VDOT) adopted standards for soil handling and amendments to improve created non-tidal wetland soil conditions. This study was conducted in sites where these new reconstruction practices were supposedly being implemented. Specific objectives were (i) to determine the relative effects of soil reconstruction practices on mitigation site soils, (ii) to assess the degree to which hydric soil indicators were present, and (iii) to evaluate the relative edaphic potential of mitigation site soils. Soil physical, chemical and morphological properties were analyzed in ten mitigation wetlands located in Virginia's Piedmont and Coastal Plain. Surface soil pH was high due to liming, although some sites demonstrated low subsoil pH, indicating the presence of sulfidic materials. Nutrient levels varied, while C:N ratios were low (<25:1), suggesting a high quality organic matter complex. Organic amendments were generally applied at a rate of 4% soil organic matter content. Actual measured carbon content was <2.6% (<50 Mg ha⁻¹). Sites not receiving organic materials and associated tillage had root-limiting bulk densities at the surface, while the majority of sites had root-limiting subsoil (30 cm) bulk densities due to weakly developed soil structure and a lack of deep ripping practices. Many sites also contained high sand content (>50%), which may negatively affect other soil properties. Nine sites had confirmed Hydric Soil Indicators, with their occurrence in a site as high as 70%. Soil reconstruction methods need to incorporate higher organic amendment rates and/or routine disking/ripping practices to improve mitigation wetland soil conditions. / Master of Science

Past research indicates that created non-tidal wetlands in the mid-Atlantic region are considerably lower in soil organic matter than native forested hydric soils. However, optimal loading rates for created wetland soil reconstruction have not been rigorously established. Our objective was to determine appropriate organic amendment loading rates for a Coastal Plain mitigation wetland based on 1) soil properties reflective of hydric soil development, 2) the formation of redoximorphic features, and 3) the growth and vigor of hydrophytic vegetation. The study contained wet (CCW-Wet) and dry (CCW-Dry) experiments, each receiving 6 compost treatments (0 Mg/ha untilled and 0, 56, 112, 224, and 336 Mg/ha tilled). Over the 1.5-year monitoring period, redox potential decreased and redoximorphic feature formation increased with compost loadings up to 112 Mg/ha. Surface bulk density decreased with loadings up to 224 Mg/ha, while no treatment differences were noted in sub-surface bulk density. In the CCW-Dry experiment, soil moisture peaked in the 224 Mg/ha treatment, while soil moisture in CCW-Wet increased consistently across all loadings. Total biomass in CCW-Wet and Betula nigra L. growth in both experiments increased with loading rate. Total biomass in CCW-Dry and Quercus palustris Muench. growth in both experiments peaked at 112 Mg/ha, although differences were not significant. Collectively, these findings indicate that 112 Mg/ha of high quality organic amendment was optimal for inducing hydric soil conditions and positive hydrophytic vegetation response. Incorporating compost at rates exceeding 112 Mg/ha is challenging and leads to higher surface elevations and redox levels in the initial growing season. / Master of Science

Las cianobacterias, microorganismos que realizan la fotosíntesis oxigénica, tienen que adaptar su metabolismo a los distintos retos ambientales a los que se enfrentan, como la limitación de nutrientes o los ciclos de luz oscuridad. Para ello, han desarrolado una serie de mecanismos de gran complejidad y alta regulación que les permiten adaptarse y sobrevivir. En este contexto, PipX, una pequeña proteína exclusiva de cianobacterias, descubierta por el grupo de investigación de genética cianobacteriana de la Universidad de Alicante, actúa como conexión, dependiente del estatus carbono/nitrógeno, entre la proteína de transducción de señales, PII, y el regulador transcripcional, NtcA. Recientemente se han descubierto otras parejas de interacción de PipX, entre las que destaca PipY, miembro de la familia de proteínas de unión a piridoxal fosfato (PLPBP) que forma un operón con PipX en la mayoría de cianobacterias, y la GTPasa de ensamblaje de ribosomas, EngA. La mayoría de estos descubrimientos se han realizado en el organismo modelo, Synechococcus elongatus PCC7942, el cual ha sido el principal objeto de estudio en esta Tesis, centrada fundamentalmente en PipX y sus parejas de interacción. Entre las aportaciones novedosas de estas Tesis se encuentran: 1. La propuesta del empleo de PipY como modelo para el estudio de miembros de la familia PLPBP/COG325; 2. La caracterización de los fenotipos de sobreexpresión de PipX y PipY, dando lugar al descubrimiento de nuevas funciones (formación de polifosfatos) y conexiones entre ellas; 3. La demostración de la existencia de interacción funcional entre EngA y PipX, y la descripción de la función de EngA en el estrés redox en cianobacterias; 4. El avance en el estudio de los terminantes moleculares de la toxicidad de PipX en ausencia de PII y el papel de esta última en el mantenimiento de los niveles intracelulares de PipX. En conclusión, esta Tesis amplía el conocimiento sobre la compleja regulación de los sistemas cianobacterianos en respuesta a distintos estímulos ambientales y, en concreto, las conexiones y el papel de PipX junto a sus antiguas y nuevas parejas de interacción.

Cooperativity between the metal center and the ligand has been shown in nature to be an important feature of systems that catalyze two-electron processes that first-row transition metals usually cannot catalyze on their own. In these cases, the ligand acts as a site of reactivity that in many instances can store electrons or react directly with substrates in solution. The design and study of systems where there is synergy between the metal and the ligand have been leveraged to catalyze polymerization and hydrogenation-type reactions as well as the activation of small molecules such as dihydrogen. Specifically, the pyridine(diimine) ligand scaffold has been reported to store up to three electrons on the ligand backbone that can later be used in catalysis. Wanting to expand on this work, we have designed and synthesized a new pincer that has redox-noninnocent properties similar to pyridine(diimine) ligands but incorporates a pyrazine ring instead of a pyridine ring to give rise to new electronic properties. Pyrazine(diimines) also have an uncoordinated 4-position nitrogen that can be further functionalized to fine-tune the electronic properties of the ligand. In Chapter II we will discuss bisligated iron(II) pyrazine(diimine) (PZDI) complexes in three different oxidation states where we used spectroscopic and computational techniques as well as comparison to known pyridine(diimine) iron(II) complexes to support our assignments of ligand-based reduction. Chapter III will focus on monoligated pyrazine(diimine) iron(II) complexes as compared to analogous pyrazine(diimine) systems where the central metal is manganese, cobalt, or nickel, as well as compare our pyrazine(diimine) iron(II) complexes to reported pyridine(diimine) iron(II) analogs. We have also synthesized a new inverted pyridine(diimine) ligand scaffold that has an NCN binding pocket, which will be discussed in Chapter IV. In the design of the inverted pyridine(diimine) ligand we have left in place the 4-position nitrogen from our previously described pyrazine(diimine) ligand, maintaining a Lewis basic site for functionalization. Overall, we hope to describe the results we observed with both monoligated and bisligated iron(II) pyrazine(diimine) complexes as well as discuss our approach to the design of and progress towards a new inverted pyridine(diimine) ligand scaffold.

Un des principaux acteurs impliqués dans la régulation du statut redox intracellulaire, permettant aux plantes de s’adapter aux contraintes environnementales, est une famille multigénique de petites (12-14 kDa) oxydoréductases ubiquistes appelées thiorédoxines (TRX). Le génome d’Arabidopsis code une vingtaine de TRX canoniques dont neuf sont plastidiales (TRX f, m, x et y). Très étudiées dans notre laboratoire par des approches biochimiques, les TRX de types f et m apparaissent réguler majoritairement l’activité d’enzymes impliquées dans le métabolisme primaire tandis que les types x et y servir principalement de substrats réducteurs d’enzymes antioxydantes. Plus récemment, une dixième TRX, proposée plastidiale et nommée TRX z, a été identifiée. Au cours de ma thèse, j’ai caractérisé cette nouvelle TRX chloroplastique montrant des propriétés physico-chimiques inhabituelles, la rendant unique. En effet, la TRX z semble interagir, via des interactions électrostatiques, avec des protéines pour former des complexes de masses moléculaires élevées, potentiellement liés aux acides nucléiques. De plus, la TRX z, dont l’expression est induite à la lumière, principalement dans les tissus photosynthétiques, est la première TRX chloroplastique qui n’est pas réduite par le système FTR à la lumière mais qui peut être réduite par les autres TRX plastidiales, suggérant une interconnexion entre ces différentes TRX. D’autre part, une recherche exhaustive de cibles de la TRX z, par deux approches spécifiques et complémentaires (protéomique et double hybride), ont révélé 90 cibles putatives de la TRX z. La plupart de ces cibles, jamais identifiées comme cibles des TRX, sont impliquées dans la réponse de défense des plantes mise en place lors de stress biotiques. Ces résultats suggèrent que la TRX z pourrait être un élément clé dans la mise en place de ces réponses. L’analyse fonctionnelle préliminaire de la TRX z au cours de la réponse immune innée conforte cette hypothèse. L’ensemble de ces résultats indique que la TRX z pourrait jouer le rôle d’une protéine senseur de l’état d’oxydoréduction de la cellule. / One of the main actors involved in regulation of the cellular redox state, which allow plant adaptation to stress environmental conditions, is a multigenic family of small (12-14 kDa) ubiquitous oxidoreductases named thioredoxins (TRX). Arabidopsis encodes around twenty canonical TRX, including nine plastidial isoforms (TRX f, m, x and y). Extensively studied in our laboratory by biochemical approaches, TRX f and m was found to mainly redox regulate the activity of enzymes involved in the primary metabolism whereas TRX x and y serve as reducing substrates for antioxidant enzymes. More recently, a tenth TRX, predicted plastidial and named TRX z, was identified. During my PhD, I have characterized this new plastidial TRX showing unusual physicochemical properties, making it unique. Indeed, TRX z seems to interact, via electrostatic bonds, with proteins to form high molecular weight complexes, potentially linked to nucleic acids. Moreover, TRX z, which is expressed in green tissues in the light, is the first plastidial TRX which is not reduced by the FTR system but which can be reduced by other plastidial TRX, suggesting an interconnection between these TRX. Furthermore, a large scale inventory of TRX z targets, by two specific and complementary approaches (proteomic and yeast two hybrid), revealed 90 putative TRX z targets. Most of these, which have never been identified as TRX targets before, are implicated in plant defense response to biotic stresses. These results suggest that TRX z might be a key player in these responses. Preliminary functional analysis of TRX z during immune innate response reinforces this hypothesis. Altogether, these results indicate that TRX z appears as an important sensor of the redox status of the cell.

La thèse est basée sur une étude pétrologique et géochimique de xénolites mantelliques provenant du centre du craton sibérien et de l’Asie centrale entre le lac Baïkal et la Mongolie. Le but est d’établir l'état redox du manteau lithosphérique continental dans ces deux domaines géodynamiques distincts (ancien craton, ceinture mobile phanérozoïque) et mettre la fugacité d’oxygène en relation avec le régime thermique et la spéciation des fluides C-O-H. Les fugacités d’oxygène sont calculées sur la base des rapports Fe2+/Fe3+ dans les minéraux (spinelles et grenats) de péridotites, obtenus par spectrométrie Mössbauer. En détail, l’étude porte sur : (i) les microstructures et la composition minéralogique et chimique des xénolites ; (ii) les rapports Fe2+/Fe3+ dans les minéraux par spectrométrie Mössbauer; (iii) les températures et pressions d’équilibration des xénolites; (iv) la fugacité d’oxygène à partir des compositions des minéraux; (v) la spéciation des fluides C-O-H coexistant avec les roches mantelliques. Les résultats supportent les trois conclusions majeures. (1) La fugacité d’oxygène dans le manteau Iithosphérique au centre du craton sibérien décroît de +1 à -4 ΔlogʄO2 (FMQ) entre 70 et 220 km, accompagnée de variations latérales significatives. (2) L’état redox du manteau lithosphérique en Asie centrale est très hétérogène avec une décroissance importante lors de la transition spinelle-grenat de +0 à -3 ΔlogʄO2 (FMQ) à 50-90 km. (3) La spéciation des fluides C-O-H évolue avec la profondeur depuis H2O-CO2 en haut du manteau vers H2O-CH4 à la limite lithosphère-asthénosphère, indépendamment du profil thermique et de l’épaisseur de la lithosphère / The thesis is based on a petrologic and geochemical study of mantle xenoliths from the central Siberian craton and the Baikal-Mongolia region of central Asia. Its goal is to establish the redox regime of the lithospheric mantle in these two domains with distinct tectonic settings and age and relate it to thermal regime and the speciation of C-0-H fluids. Oxygen fugacity is calculated based on Fe2+/Fe3+ ratios in spinel and garnet of mantle peridotites obtained by Mössbauer spectroscopy. The study deals with the following topics: (i) microstructures, chemical and mineralogical composition of the xenoliths; (ii) Fe2+/Fe3+ ratios in minerals by Mössbauer spectroscopy; (iii) equilibration temperatures and pressures using mineral thermo-barometry; (iv) oxygen fugacity from mineral compositions using oxybarometry; (v) proportions of molecular components in C-0-H fluids coexisting with the studied rocks. The three main conclusions of this study are: (1) Oxygen fugacity in the lithospheric mantle in the central Siberian craton decreases from +1 to -4 ΔlogʄO2 (FMQ) at depths from 70 to 220 km and shows significant lateral variations. (2) The lithospheric mantle beneath the Baikal-Mongolia region shows important redox heterogeneities, with a sharp decrease in oxygen fugacity (from +0 to -3 AlogfO2 (FMQ)) during the transition from the spine! to garnet facies peridotites at 50 to 90 km. (3) The speciation of C-O-H fluids changes with depth from essentially H2O-CO2 in the shallow lithospheric mantle to H2O-CH4 at the lithosphere-asthenosphere boundary regardless of the thermal state and the thickness of the lithosphere

Les propriétés géochimiques particulières du molybdène vis-à-vis du potentiel d’oxygénation en milieu aqueux en font un élément particulièrement utilisé pour déterminer le degré d’oxygénation du milieu dans lequel un dépôt a sédimenté. Dans un premier temps, ce travail de thèse présente une alternative aux méthodes d’extraction du molybdène utilisées jusqu’ici. Les principales méthodes de purification couramment utilisées sur échantillons géologiques se décomposent en deux phases : une purification au travers d’une résine anionique, puis une purification au travers d’une résine cationique. La méthode proposée ici, initialement prévue pour permettre des analyses en Sample-Standard-Bracketing (SSB), permet d’isoler quantitativement le molybdène du reste de la matrice géologique en un seul passage sur résine anionique. La purification s’avère également suffisamment efficace pour effectuer des analyses en utilisant la méthode du double-spike. Une comparaison de ces deux méthodes de correction du fractionnement instrumental a permis d’évaluer les limites de l’utilisation du SSB par rapport au double-spike. Dans un second temps, cette chimie a été appliquée dans le cadre d’une étude géochimique approfondie d’un gisement fossilifère extrêmement riche: le Lagerstätte de Sirius Passet situé au nord du Groenland. Associée aux critères paléontologiques, cette étude indique que ces sédiments se sont déposés dans un milieu au moins partiellement oxygéné, sous forme de boues sédimentaires très peu propices aux échanges avec la colonne d’eau. Le contexte paléogéographique, les analyses chimiques et les observations microscopiques suggèrent que ces boues sont principalement d’origine éolienne. / The particular behaviour of molybdenum towards the oxygenation potential in aqueous environments makes this element very useful to infer the oxygenation level under which a sediment is deposited. The first part of this PhD thesis is dedicated to the development of a new protocol for the extraction of molybdenum from geological samples. Until now, most extractions are performed using two ion exchange resin columns: an anionic one, then a cationic one. The protocol proposed here, initially set to allow measurements using a classical Sample-Standard-Bracketing (SSB) method, allows good purification and recovery of molybdenum through a single pass in an anion exchange resin. This purification is good enough to perform analyses using the double-spike method. A comparison between these two methods to correct the instrumental mass bias allowed us to better constrain SSB limits versus the double-spike method. The second part of this work aimed at geochemically characterizing an extraordinary fossil assemblage deposit located in North Greenland: the Sirius Passet Lagerstätte. In association with paleontological criteria, this study shows that these sediments were deposited in an environment at least partially oxygenated, in the form of muds enabling little exchange with the water column. The paleogeographical context, chemical analyses and thin-section observations suggest that these muds are mainly aeolian in origin.

O diabetes gestacional (DG) é uma condição definida como intolerância a carboidratos e hiperglicemia, com início no segundo trimestre da gravidez. Trabalhos desenvolvidos por nosso grupo mostraram que a progesterona (PG) é capaz de causar a morte de células pancreáticas, por um mecanismo dependente da geração de radicais livres, o que poderia contribuir para o desenvolvimento do DG. O objetivo desse trabalho foi estudar o efeito da PG, na presença ou não de antioxidantes, na expressão de genes relacionados ao estresse oxidativo e na defesa oxidante em células pancreáticas da linhagem RINm5F. As células foram incubadas com PG 0,1, 1,0 e 100 &#181M por 6 ou 24 h, na presença ou não dos antioxidantes vitamina E e C. Após a incubação, foram realizados ensaios de viabilidade celular e fragmentação do DNA. A PG, não causou perda da integridade da membrana das células RINm5F, porém, ela promoveu fragmentação do DNA em, aproximadamente, 40% das células RINm5F e MCF-7 (controle positivo), enquanto que os antioxidantes vitamina E e C reduziram tal fragmentação. A partir da extração do RNA e síntese de cDNA foi investigada a expressão de 84 genes envolvidos no estresse oxidativo e defesa antioxidante. Dos 84 genes, cinco deles tiveram sua expressão aumentada em no mínimo, duas vezes em, pelo menos, duas concentrações diferentes, independentemente do tempo de incubação, ou nas mesmas concentrações em tempos diferentes, como os que codificam para a proteína de choque térmico a1a (Hspa1a), glutationa peroxidase 6 (Gpx6), dual oxidase 1 (Duox1), heme oxigenase 1(Hmox1) e estearoil-CoA desaturase 1 (Scd1). Esses genes, juntamente com a peroxirredoxina 4 (Prdx4), desempenham importante papel na fisiologia da célula pancreática e/ou DG. A expressão desses genes também foi estudada na pré-incubação das células RINm5F com as vitaminas E e C. Tais antioxidantes, de forma geral, foram capazes de aumentar a expressão de Hmox1 e Prdx4, genes com funções antioxidantes, e de diminuir de Scd1, um gene com função pró- oxidante. Ao nível citoplasmático, verificou-se que as quantidades das proteínas Hmox1 e Prdx4 também foram moduladas pela da PG e/ou vitamina E e C. Os resultados sugerem que esses antioxidantes apresentam importante papel na proteção da células RINm5F contra o dano oxidativo induzido pela PG. Desta forma, os resultados obtidos nesse projeto, em conjunto, devem colaborar para melhor compreensão da patogênese do DG, abrindo novas perspectivas não só para elucidação do mecanismo molecular envolvido na ação da PG sobre células pancreáticas e sua relação com o DG, mas para o desenvolvimento de estratégias de prevenção e tratamento dessa doença baseadas na terapia com antioxidantes / Gestational diabetes (GD) is a condition defined as carbohydrate intolerance and hyperglycemia, beginning in the second trimester of pregnancy. Studies developed by our group have shown that progesterone (PG) is able to cause pancreatic cells death, by a mechanism dependent on the generation of free radicals, which could contribute to the development of GD. The aim of this work was to study the effect of PG, in the presence or absence of antioxidants, on the expression of genes related to oxidative stress and oxidant defense in pancreatic cells of the RINm5F lineage. Cells were incubated with 0.1, 1.0 and 100 µM PG for 6 or 24 h, in the presence or absence of vitamin E and C antioxidants. PG did not cause loss of membrane integrity of RINm5F cells, however, it promoted DNA fragmentation in approximately 40% of the RINm5F and MCF-7 cells (positive control), whereas vitamin E and C antioxidants reduced such fragmentation. From the RNA extraction and cDNA synthesis was investigated the expression of 84 genes involved in oxidative stress and antioxidant defense. Among of 84 investigated genes, five of them had their expression increased, in the minimum 2-fold in, at least, two different concentrations independent of incubation time (6 or 24 h), or at the same concentrations at different times, such as those that encoding for heat shock protein a1a (Hspa1a), glutathione peroxidase 6 (Gpx6), dual oxidase 1 (Duox1), heme oxygenase 1 (Hmox1) and stearoyl-CoA denaturase 1 (Scd1). These genes, together with the peroxiredoxin 4 (Prdx4), play an important role in pancreatic cell physiology and/or DG. The gene expression was also studied in the preincubation of RINm5F cells with vitamin E and C. These antioxidants were generally able to increase the Hmox1 and Prdx4 expression, genes with antioxidant functions, and decrease the Scd1 expression, a gene with pro-oxidant function. At the cytoplasmic level, it was found that the amounts of Hmox1 and Prdx4 proteins were also modulated by PG and / or vitamin E and C. The results suggest that these antioxidants play an important role in the RINm5F protection cells against the oxidative damage induced by PG. Thus, the results obtained in this project, together, should contribute to a better understanding of the pathogenesis of DG, opening new perspectives not only to elucidate the molecular mechanism involved in the action of PG on pancreatic cells and its relationship with DG, but for the development of strategies for the prevention and treatment of this disease based on antioxidant therapy