Magistro darbe tiriama pušies žėlimo ypatumai pušynuose po neplynųjų kirtimų kirtavietėse nederlingose augavietėse Pašvenčio girininkijoje. Darbo objektas – šešios neplynųjų kirtimų kirtavietės nederlingoje augavietėje Pašvenčio girininkijoje. Darbo tikslas – įvertinti Pašvenčio girininkijos pušies žėlimo kokybę ir jį sąlygojančius veiksnius neplynųjų kirtimų pušynų kirtavietėse Nb augavietėje. Darbo metodai – tyrimai vykdyti 3–8 metų Pašvenčio girininkijos neplynųjų kirtimų kirtavietėse, kuriose buvo tolygiai išdėstytos apskaitos aikštelės sąlyginai vienodais atstumais sklypų įstrižainių kryptimis, siekiant atlikti žėlinių apskaitą ir įvertinti jų kokybę. Matavimai atlikti kirtaviečių sklypuose pasirenkant po 20 m2 arba 10 m2 apskaitos aikšteles. Kiekvienoje apskaitos aikštelėje atlikti šie vertinimai: savaiminukų rūšis ir gausa, savaiminukų gyvybingumas, žolinės dangos agresyvumo laipsnis, ligos. Gautų duomenų apdorojimui, t. y. grafiniam duomenų atvaizdavimui, buvo naudojama Microsoft Excel programa. Darbo rezultatai – apibendrinus gautus duomenis nustatyta, kad Pašvenčio girininkijoje atlikus neplynuosius kirtimus, pušynuose žėlimas vyksta gerai visose tirtose kirtavietėse. Nagrinėtose 6 kirtavietėse vidutinis žėlinių tankis N vid. = 7998 vnt./ha. Pagal rūšinę sudėtį, visose kirtavietėse dominuoja pušies savaiminukai, sudarydama 60– 90% visų medelių ir po kelis procentus – eglės ir beržai. Kirtavietės amžius turi svarbią įtaką pomiškio susiformavimui. Didžiausias pušies... [toliau žr. visą tekstą] / The Master’s thesis analyses peculiarities of pine forests sprouting after non smooth traverse in infertile growth place of Pasventys forestry district. Object of the thesis – The object of the work: six non smooth traverses in infertile growth place in Pasventys forestry district. Aim of the thesis – The aim of the work: is to assess the quality of Pasventys forestry district sprouting and factors causing accidental traverse in pine forests, in infertile growth place. Methods of the research – researches were performed in the non smooth deforestation zones, dating the period of 3–8 years, in Pasventys forestry district. Each non smooth cutting area was divided into equal distances in diagonal directions while trying to do accounting as well as to evaluate their quality. The measurements were performed in 20 to 10 meters accounting fields. The following assessments were performed in each of the recording sites: spontaneous type and their abundance, vitality of spontaneous type, the level of aggression while speaking about grass cover. Microsoft Excel was used for the received data processing, e. i. for graphic representation of data. Results of the thesis – The results of the research: summary of the research found that the spontaneous of pine forestry in Pasventys forestry district performs well in all observed cutting places. The estimated average density of all six cutting places is 7998 units per ha. The self-contained pine is a dominated type consisting 60-90% of all... [to full text]

Telomerase reverse transcriptase (TERT) is the catalytic subunit of telomerase and the limiting factor for the enzyme activity. The expression of TERT and telomerase activity is increased in atherosclerotic plaques. However, the role of TERT dysregulation during atherosclerosis formation remains unknown. The work herein first identified a multi-tiered regulation of TERT expression in smooth muscle cells (SMC) through histone deacetylase (HDAC) inhibition. HDAC inhibition induces TERT transcription and promoter activation. At the protein level in contrast, HDAC inhibition decreases TERT protein abundance through enhanced degradation, which decreases telomerase activity and induces senescence. Furthermore, during vascular remodeling in vivo, TERT protein expression in the neointima is prevented by HDAC inhibition. These data illustrate a differential regulation of TERT transcription and protein stability by HDAC inhibition. TERT is highly expressed in replicating SMC of atherosclerotic and neointimal lesions. Using a model of guidewire-induced arterial injury, neointima formation was reduced in TERT-deficient mice. Studies in SMC isolated from TERT-deficient and TERT overexpressing mice with normal telomere length established that TERT is necessary and sufficient for cell proliferation. TERT deficiency did not induce a senescent phenotype but resulted in G1 arrest albeit hyperphosphorylation of the retinoblastoma protein. This proliferative arrest was associated with stable silencing of the E2F1-dependent S-phase gene expression program which could not be reversed by ectopic overexpression of E2F1. Chromatin immunoprecipitation and accessibility assays revealed that TERT was recruited to E2F1 target sites to increase chromatin accessibility for E2F1 by facilitating the acquisition of permissive histone modifications. These data indicate a mitogenic effect of TERT on SMC growth and neointima formation through epigenetic regulation of proliferative gene expression. Furthermore, TERT expression is induced in activated macrophages during experimental and human atherosclerosis formation. To investigate the role for TERT in lesional macrophages and the subsequent effect on atherosclerosis formation, TERT-deficient mice were crossbred with LDL-receptor-deficient (LDLr-/-) mice to generate first generation G1TERT-/-LDLr-/- offsprings, which were then further intercrossed to obtain third generation G3TERT-/-LDLr-/- mice. G1TERT-/-LDLr-/- mice revealed no telomere shortening while severe telomere attrition was evident in G3TERT-/-LDLr-/- mice. When fed an atherogenic diet, G1TERT-/-LDLr-/- and G3TERT-/-LDLr-/- mice were both protected from atherosclerosis formation compared to their wild-type controls, indicating that genetic TERT-deletion prevents atherosclerosis, and formation of the disease is not affected by telomere attrition. Similarly, atherosclerosis development was decreased in chimeric LDLr-/- mice with TERT deletion in hematopoietic stem cells after bone marrow transplantation. TERT deficiency reduced macrophage accumulation in atherosclerotic lesions and altered chemokine expression, including CXC1/2/3, CCL3, CCL5, CCL21, CCR7, IL-6, and IL-1α. In isolated macrophages, gene ontology (GO) enrichment analysis of silenced inflammatory genes indicated that TERT positively regulates signal transducer and activator of transcription (STAT) cascade, which was confirmed by the decreased tyrosine phosphorylation of STAT3 protein resulting from TERT deletion. These findings indicate genetic TERT deficiency decreases atherosclerosis formation by silencing inflammatory chemokine transcription through inactivation of the STAT3 signaling pathway in activated macrophages. In conclusion, the dysregulation of TERT expression within atherosclerotic plaques plays a causative role for vascular remodeling, including injury-induced neointima formation and hypercholesterolemia-induced atherosclerosis, through inducing SMC proliferation and a pro-inflammatory phenotype in infiltrating macrophages. These findings unveil a mechanism of TERT exacerbating the pathological vascular remodeling, which may provide a novel therapeutic target to combating vascular diseases.

In an effort to assess the predictive ability of exchange rate models when data on African countries is sampled, this paper studies nonlinear modelling and prediction of the nominal exchange rate series of the United States dollar to currencies of thirty-eight African states using the smooth transition autoregressive (STAR) model. A three step analysis is undertaken. One, it investigates nonlinearity in all nominal exchange rate series examined using a chain of credible statistical in-sample tests. Significantly, evidence of nonlinear exponential STAR (ESTAR) dynamics is detected across all series. Two, linear models are provided another chance to make it right by shuffling to data on African countries to investigate their predictive power against the tough random walk without drift model. Linear models again failed significantly. Lastly, the predictive ability of nonlinear models against both the random walk without drift and the corresponding linear models is investigated. Nonlinear models display useful forecasting gains over all contending models.

Cyclic 3',5'-guanosine monophosphate (cGMP) is a key signaling molecule involved in a myriad of physiological processes, including vascular smooth muscle (VSM) tone, water- and electrolyte homeostasis, platelet aggregation, airway smooth muscle tone, smooth muscle proliferation and bone formation. Increased occurrence of vascular disorders including erectile dysfunction, hypertension, stroke and coronary artery disease, have made it increasingly important to study the dynamic interplay between cGMP synthesis and hydrolysis in VSM cells. This dissertation examines the spatial distribution of intracellular cGMP, [cGMP]i, in response to NO and atrial natriuretic peptide (ANP) in VSM cells. To investigate the spatial patterning of [cGMP]i, we have developed a new generation of non-FRET (fluorescence resonance energy transfer) cGMP biosensors that are suitable to monitor [cGMP]i in response to physiological (low-nanomolar) NO and ANP concentrations and that qualify for real-time, confocal imaging techniques. We have termed these indicators FlincGs, for green fluorescent indicators of cGMP. For the development of FlincGs, we made use of the specific cGMP binding characteristics of PKG. We utilized site-specific mutagenesis, kinetic cGMP binding, dissociation and kinase assays, as well as crystallography, in order to investigate PKG activation and cGMP binding dynamics in greater detail. Based on these studies, our novel, non-FRET cGMP biosensors were designed by attaching cGMP binding fragments of PKG to the N-terminus of circular permutated green fluorescent protein. We applied FlincGs in cultured VSM cells as well as in intact tissue to determine whether two spatially distinct populations of guanlylyl cyclase (cytosolic versus membrane bound) underlie the generation of spatiotemporally-specific patterns of [cGMP]i formation.

Cette thèse se compose de deux parties, concernant deux études expérimentales sur les mouvements oculaires de poursuite lente d'un stimulus visuel en mouvement (barre inclinée). La première étude aborde l'intégration dynamique de signaux locaux de mouvement visuel provenant de la rétine, tandis que la seconde porte sur l'influence de signaux extra-rétiniens sur l'intégration du mouvement. Un cadre théorique plus général est également proposé, sur la base d'un modèle bayésien récurrent et hiérarchique pour la poursuite lente. Pour la première étude, l'intégration dynamique de mouvement a été analysée en variant le contraste et la vitesse de la barre inclinée. Les résultats montrent que des vitesses plus élevées et des valeurs plus basses de contraste produisent un plus fort biais dans la direction initiale de poursuite et que successivement la dynamique d'intégration de mouvement est plus lente pour les contrastes faibles. Une version en boucle ouverte d'un modèle bayésien est proposée, où un réseau bayésien récurrent est connecté en cascade avec un modèle du système oculomoteur pour générer des réponses de poursuite lente. Les réponses du modèle reproduisent qualitativement les différentes dynamiques observées dans les réponses de poursuite à la barre inclinée en fonction des vitesses et des contrastes différents. La deuxième étude a enquêté sur les interactions dynamiques entre les signaux rétiniens et extra-rétiniens dans l'intégration dynamique de mouvement pour la poursuite lente par le moyen d'une suppression transitoire de la cible à différents moments de la poursuite, et notamment au cours de la phase de boucle ouverte et pendant l'état d'équilibre. / This thesis addresses two studies by studying smooth pursuit eye movements for a translating tilted bar stimulus. First, the dynamic integration of local visual motion signals originating from retina and second, the influence of extra-retinal signals on motion integration. It also proposes a more generalized, hierarchical recurrent bayesian framework for smooth pursuit. The first study involved investigating dynamic motion integration for varying contrasts and speeds using a tilted bar stimuli. Results show that higher speeds and lower contrasts result in higher initial direction bias and subsequent dynamics of motion integration is slower for lower contrasts. It proposes an open-loop version of a recurrent bayesian model where a recurrent bayesian network is cascaded with an oculomotor plant to generate smooth pursuit responses. The model responses qualitatively account for the different dynamics observed in smooth pursuit responses to tilted bar stimulus at different speeds and contrasts. The second study investigated the dynamic interactions between retinal and extra-retinal signals in dynamic motion integration for smooth pursuit by transiently blanking the target at different moments during open-loop and steady-state phases of pursuit. The results suggest that weights to retinal and extra-retinal signals are dynamic in nature and extra-retinal signals dominate retinal signals on target reappearance after a blank introduced during open-loop of pursuit when compared to a blank introduced during steady-state of pursuit. The previous version of the model is updated to a closed-loop version and extended to a hierarchical recurrent bayesian model.

Nous avons étudié l’expression et la régulation de la lipogenèse dans les aortes et CMLV et déterminé si elle est modifiée par l’insulino-résistance et le diabète. Les rats Zucker obèses (ZO), diabétiques et Psammomys obesus accumulent plus de lipides dans leurs aortes que leurs contrôles. Cependant l’expression des gènes de la lipogenèse et ceux impliqués dans la captation des acides gras, n’est pas augmentée. Un résultat similaire a été retrouvé dans des pièces d’endartériectomies chez l’homme. Le milieu adipogénique, le glucose ou l’insuline seule stimulent modérément la lipogenèse uniquement dans les CML de Zucker contrôles, aucun effet n’a été observé dans les CML de ZO. Nous avons montré que les effets du TO901317 sur la lipogenèse dans les CMLV sont dus uniquement à l’activation du récepteur nucléaire LXRα, PXR n’a aucun effet. En conclusion, la lipogenèse n’est pas augmentée dans la paroi artérielle durant l’insulino-résistance et le diabète. / We investigated the expression and regulation of lipogenesis in aortas and VSMC and determined if it is modified during metabolic abnormalities. Zucker obese (ZO), diabetic (ZDF) rats, and the high fat diet fed Psammomys obesus accumulated more triglycerides in their aortas than control rats. However the expression of lipogenic genes, or of genes involved in fatty acids uptake, was not increased. Lipogenesis was not increased in human carotid endarterectomy of diabetic compared to non-diabetic patients. The adipogenic medium (ADM), glucose or insulin stimulated moderately lipogenesis but only in VSMC from control rats. No effect was observed in VSMC from ZO. We showed that the lipogenic effects of TO901317observed in VSMC from Zucker control rats are due solely to the nuclear receptor LXRα, PXR agonist had no effect. Conclusion: Lipogenesis is not increased in arterial wall during insulin-resistance and diabetes.

La cellule musculaire lisse (CML) a un rôle pivot dans la physiopathologie de l’asthme. Dans ce travail de thèse nous avons pu mettre en avant l’implication du récepteur de type 2 activé par les protéases (PAR-2) dans une composante majeure du remodelage bronchique : la prolifération musculaire lisse. Dans le premier travail, nous avons montré une augmentation de l’expression du PAR-2 au niveau des CML bronchiques d’asthmatiques in vitro. La réponse calcique est dépendante du niveau d’expression du récepteur, mais n’influence pas la réponse proliférante. La stimulation répétée du PAR-2 augmente la prolifération des seules CML d’asthmatiques, par un mécanisme dépendant de la voie ERK. Dans le second travail, nous avons montré que la production basale d’un épithélium reconstitué entraine une prolifération plus importante des CML d’asthmatiques comparée aux CML de témoins. Une augmentation supplémentaire de la prolifération des seules CML d’asthmatiques a été observée, après activation par le surnageant d’épithélium stimulé par des acariens de maison comparé au surnageant épithélial non stimulé. Ce mécanisme est dépendant du PAR-2 épithélial, qui induit la production de leucotriènes C4, sur des CML dont l’expression du récepteur (CysLTR1) est augmentée chez l’asthmatique. Ces résultats apportent de nouvelles connaissances dans le remodelage musculaire lisse bronchique de l’asthmatique et met en avant le PAR-2 comme cible thérapeutique potentielle. / Smooth muscle cells (SMC) play an important role in asthma pathophysiology. In this thesis, we have highlighted the involvement of protease activated receptor type-2 (PAR-2) in SMC proliferation, which is a major component of airway remodeling. In the first study, we have shown an increased expression of PAR-2 in asthmatic bronchial SMC in vitro. Calcium response is dependent on the expression level of PAR-2, which does not affect the proliferative response. Repeated stimulation of PAR-2 increases the proliferation of asthmatics SMC only, by an ERK-dependent mechanism. In the second study, we have demonstrated that the basal production of reconstituted epithelium leads to a greater proliferation of asthmatics SMC compared to controls. Increased proliferation of asthmatics SMC only was observed, after stimulation with supernatant of the epithelium stimulated by house dust mites (HDM) compared to unstimulated epithelial supernatant. This mechanism is epithelial PAR-2-dependent, which induces the production of leukotrienes C4, whose receptor expression (CysLTR1) is increased in asthmatics SMC. These results provide new insights into bronchial smooth muscle remodeling in asthma and highlights the PAR-2 as a potential therapeutic target.

Nous étudions dans ce travail une méthode de type éléments finis dans le but de simuler le mouvement de particules rigides immergées. La méthode développée ici est une méthode de type domaine fictif. L'idée est de chercher un prolongement régulier de la solution exacte à tout le domaine fictif afin d'obtenir une solution régulière sur tout le domaine et retrouver l'ordre optimal de l'erreur avec des éléments d'ordre 1. Le prolongement régulier est cherché en minimisant une fonctionnelle dont le gradient est donné par la solution d'un nouveau problème fluide faisant intervenir une distribution simple couche dans le second membre. Nous faisons une analyse numérique, dans le cas scalaire, de l'approximation de cette distribution par une combinaison de masse de Dirac. Un des avantages de cette méthode est de pouvoir utiliser des solveurs rapides sur maillages cartésiens tout en conservant l'ordre optimal de l'erreur. Un autre avantage de la méthode vient du fait que les opérateurs ne sont pas modifiés, seul les seconds membres dépendent de la géométrie du domaine initial. Nous avons de plus écrit un code C++ parallèle en deux et trois dimensions, permettant de simuler des écoulements fluide/particules rigides avec cette méthode. Nous présentons ainsi une description des principales composantes de ce code. / In this work, we study a finite element method in order to simulate the motion of immersed rigid bodies. This method is of the fictitious domain type. The idea is to look for a smooth extension in the whole domain of the exact solution and to recover the optimal order obtain with a conformal mesh. This smooth extension is sought by minimizing a functional whose gradient is the solution of another fluid problem with a single layer distribution as a right hand side. We make the numerical analysis, in the scalar case, of the approximation of this distribution by a sum of Dirac masses. One of the advantage of this method is to be able to use fast solvers on cartesian mesh while recovering the optimal order of the error. Another advantage of this method is that the operators are not modified at all. Only the right hand side depends on the geometry of the original problem. We write a parallel C++ code in two and three dimensions that simulate fluid/rigid bodies flows with this method. We present the core blocks of this code to show how it works.

O procedimento de dimensionamento de uma linha lateral de microirrigação necessita avaliar com precisão as perdas de carga distribuídas na tubulação e as perdas de carga localizadas nas inserções dos emissores com os tubos. Estas perdas localizadas podem ser significativas quando comparadas com as perdas de carga totais, devido ao grande número de emissores instalados ao longo da linha lateral. Este trabalho reporta os resultados de um experimento sobre perda de carga distribuída, fator de atrito e perda de carga localizada em conexões de emissores &#34;on-line&#34; em tubos de polietileno de pequeno diâmetro. Foram utilizados cinco tubos com diâmetros internos de 10,0 mm, 13,0 mm, 16,3 mm, 17,4 mm e 19,7 mm. O experimento foi conduzido para números de Reynolds no intervalo de 5000 a 68000, obtidos pela variação da vazão nos tubos, a uma temperatura média da água de 20 &#177; 2 &#176;C. Os resultados foram analisados e concluiu-se que o fator de atrito f da equação de Darcy-Weisbach pode ser estimado com c = 0,300 e m = 0,25. A equação de Blasius com c = 0,316 e m = 0,25 mostrou-se conservadora na estimativa do fator de atrito, porém esse fato não constitui limitação para sua utilização em projetos de microirrigação. As análises mostraram que as duas equações proporcionam estimativas de f com pequeno desvio médio (5,1%). Para um dado conjunto tubo-conexão o coeficiente de carga cinética (KL) foi praticamente independente do número de Reynolds, para R>20000, sugerindo que cada conjunto tubo-conexão pode ser caracterizado por um valor médio de KL. Para desenvolver um procedimento de estimativa de KL, a geometria da conexão entre o emissor e o tubo foi caracterizada por um índice de obstrução IO, que depende da razão (r) entre a área da seção transversal do tubo, onde o conector está localizado, e a área da seção transversal do tubo fora do conector. Uma função potência foi ajustada aos pares experimentais (IO, KL). A seleção do modelo é consistente com o fenômeno físico uma vez que KL = 0 para r = 1 (nenhuma obstrução dentro do tubo). Para 5000<R68000 a relação foi KL = 1,23 (IO)0,51 com R2 = 0,9556 e erro padrão do ajuste igual a 0,04245. As diferenças entre os valores de KL estimados e observados são normalmente distribuídas. / Microirrigation lateral design procedure needs to accuratel evaluation of both the pipe head losses and the local losses that are due to the protrusion of emitter barbs into the flow. These local losses, in fact (in relation to the high number of emitters located along the line) can become significant compared to the overall energy loss. On this paper, the results of an experimental study on the pipe head losses, friction factor and head local losses for small-diameters polyethylene pipes are reported. The experiment was carried out using a range of Reynolds number between 5000 to 68000, obtained by varying discharge at 20 &#177; 2 &#176;C water temperature, with a internal diameter pipes of 10,0 mm, 13,0 mm, 16,3 mm, 17,4 mm and 19,7 mm. According to the results analysis and experimental conditions the friction factor (f) of the Darcy-Weisbach equation can be estimated with c = 0,300 and m = 0,25. The Blasius equation (c = 0,316 and m = 0,25) gives a conservative estimative of f, although this fact is non restrictive for microirrigationsystem design. The analysis shows that both the Blasius and the adjusted equation parameters allow accurate friction factor estimate, characterized by low mean error (5,1%). For a given pipeconnection system, the fraction KL of kinetic head was practically independent of the Reynolds number, for R>20000, which suggested that each system can be characterized by the mean value of KL. To derive an estimating procedure of KL, the geometry of the connection between the emitter and the pipe was characterized by the obstruction index IO, which is dependent on the ratio (r) between the pipe cross-section area corresponding to the section in which the emitter is located, and the pipe cross-section area. A power relationship was then fitted to the experimental IO, KL data pairs. The selection form of thr relationship is consistent with the physical phenomenon since it estimates KL = 0 for r = 1 (no obstruction into the pipe). For 5000<R<68000 the relationship was KL = 1,23 (IO)0,51 with R2 = 0,9556 and standard fit error equal to 0,04245. The differences between KL observed values and the calculated ones are normally distributed.

Processos celulares que governam as NADPH oxidases vasculares em condições patológicas não estão claros ainda. Como os processos redox são parte intrínseca da resposta da célula ao estresse, temos investigado se o estresse oxidativo pode convergir com outros tipos de estresse via Nox(es). No presente estudo, focamos na inibição do proteasoma como uma condição relevante de estresse. A incubação de células musculares lisas com concentrações não apoptóticas de inibidores do proteasoma, MG132 e lactacistina, promoveu aumento na produção basal de superóxido e na atividade da NADPH oxidase, diminuição da atividade da SOD e da razão GSH/GSSG. Por outro lado, a inibição do proteasoma diminui a atividade da Nox após estímulo com Angiotensina II ou Tunicamicina, conhecido estressor do retículo endoplasmático. Em condições basais, MG132 induz a expressão de mRNA da Nox1, entretanto o aumento de Nox1 induzido por Angiotensina II foi diminuído na presença de MG132. O mesmo efeito ocorre com a indução de Nox4 pela Tunicamicina, que nesse caso foi drasticamente reduzida na presença de MG132. Além disso, tanto Angiotensina II quanto Tunicamicina induziram a atividade lítica do proteasoma 20S. A seguir, investigamos as conseqüências fisiológicas do MG132 na sinalização do estresse do RE, uma conhecida resposta mediada por Nox4. Células vasculares incubadas com MG132 induzem a expressão de marcadores do estresse do RE, GRP78 e XBP1, e também os marcadores mais tardios ATF4 e o próapoptótico CHOP/GADD153. Resultados similares ocorrem também com a Tunicamicina. Entretanto, a co-incubação de Tunicamicina e MG132 diminui e a sinalização do estresse do RE. AKT e p38 MAPK foram ativados por MG132, possivelmente como resposta ao estresse induzido pela inibição do proteasoma. Assim, a inibição do proteasoma bloqueia a NADPH oxidase, com aumento da atividade basal e expressão da Nox1 versus forte inibição da ativação e expressão da Nox4 frente ao estímulo. A inibição da Nox4 associa-se e pode contribuir para a inibição pelo MG132 da sinalização do estresse do RE. Portanto, o proteasoma parece exercer papel na integração de estresses celulares envolvendo a NADPH oxidase. A inibição do proteasoma pode ter papel na terapia de doenças associadas a estresse do RE. / Cellular processes governing vascular Nox family NADPH oxidases in disease conditions are unclear. Since redox processes are intrinsic to cell stress response, we asked whether oxidative stress merges with other types of stress via Nox(es). We focused on proteasome inhibition as a relevant stress condition. Vascular smooth muscle cells (VSMC) incubation with non-apoptotic concentrations of proteasome inhibitors MG132 or lactacystin promoted increased baseline superoxide generation (HPLC/DHE products) and NADPH oxidase activity, decreased SOD activity and GSH/GSSG ratio. Conversely, proteasome inhibitors decreased by Nox response to Angiotensin II (AngII) and abrogated Nox response to endoplasmic reticulum (ER) stressor tunicamycin. With MG132, basal Nox1 mRNA levels were increased, while Nox1 response to AngII was blunted. Moreover, MG132 abolished Nox4 mRNA levels TN-induced. Both AngII and TN (at 2 and 4 hs) promoted increased 20S proteasome lytic activity. We next assessed physiological consequences of MG132 in ER stress signaling, a known Nox4- mediated response. VSMC incubation with MG132 alone enhanced expression of the ER stress markers Grp78 and XBP1 and late markers such as ATF4 and proapoptotic CHOP/GADD153. Similar results occurred with the known ER stressor TN. However, co-incubation of TN and MG132 decreased Grp78, Grp94 and CHOP/GADD153, indicating that proteasome inhibition interrupts ER stress. AKT and p38 are activated by MG132 as response to stress and recover to survival. Thus, proteasome inhibition disrupts NADPH oxidase, with increased baseline activity and Nox1 expression vs. strong inhibition of stimulated Nox1 and Nox4 activation/expression. The later effect may underlie MG132-mediated inhibition of ER stress signaling. (Support: FAPESP, CNPq Milênio Redoxoma)