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<p>[missing page:45]</p> / <p>BACKGROUND: Creatine monohydrate (CrM) supplementation during resistance exercise results in a greater increase in fat free mass (FFM), total body mass (TBM), and strength in young men and women. The purpose of the present investigation was to examine the interactive effects of creatine supplementation and resistance training on body composition, strength, and intramuscular total creatine concentration in older men and women.</p> <p>METHODS: Twenty-eight older men and women were randomly allocated, in a double blind fashion, to receive either CrM (n=14; CrM: 5g + 2g dextrose) or placebo (n=14; PL: 7g dextrose). Subjects participated in a 14 wk progressive, whole-body resistance training program. Pre-and post-training measurements included: 1 RM strength, isometric strength, body composition (TBM, FFM, %BF), muscle fiber area, and muscle total creatine and phosphocreatine.</p> <p>RESULTS: Training resulted in an increase in 1 RM strength for each of the 4 exercises (range = 26 - 60%) (p < 0.001), an increase in knee and dorsiflexion isometric strength (p < 0.001) and an improvement of performance on functional tasks (p < 0.001). Knee isometric strength was increased more for CrM (46.2%) as compared to PL (22.5%) (p < 0.05). Total body mass and lean body mass increased more for CrM (TBM: +1.2 kg; LBM: +1.7 kg) as compared to PL (TBM: -0.2 kg; LBM: 0.4 kg) (p < 0.05)</p> <p>CONCLUSIONS: We conclude that erM supplementation results in a greater increase in isometric knee extensor strength, total body mass and lean body mass during resistance training in older adults.</p> / Master of Science (MSc)

Resistance exercise training (RET) and protein supplementation are potent nonpharmacological countermeasures against sarcopenic muscle and strength loss, however other exercise modalities and isolated nutritional supplements are effective in combating additional deleterious age-related changes, such as reduced cardiometabolic health. Accordingly, in Study 1 we assessed the 48-hour integrated muscle protein synthesis (MPS) response to a single session of RE, aerobic exercise, or high-intensity interval exercise (HIIE) in a group of healthy older men using the novel heavy water method. The results of Study 1 indicated that both RE and HIIE were capable of significantly elevating myofibrillar MPS above resting rates, with the most substantial effect observed following RE. In Studies 2 and 3 we evaluated whether daily consumption of a nutritional supplement which comprised whey protein, creatine, vitamin D/calcium, and omega-3 polyunsaturated fatty acids could: augment strength, physical function, and lean tissue mass (Study 2), and also improve glycemic control, lipidemia, and systemic inflammation (Study 3) in healthy older men following 6 weeks of supplementation in the absence of exercise; and enhance exercise training-induced improvements in the same outcomes following a 12-week RET + HIIT program. Six weeks of multi-ingredient nutritional supplementation stimulated gains in strength (~6%) and lean mass (~1%), roughly equivalent to one year's worth of age-related decline, as well as reduced circulating concentrations of lipids and inflammatory markers. Twelve weeks of combined RET + HIIT simultaneously improved strength, aerobic fitness, and glucose handling in the same group of older men. Further improvements in systemic inflammation and glucose handling were observed when multi-ingredient nutritional supplementation was combined with exercise training. Collectively, these studies demonstrate that multiple exercise modalities and nutritional supplements can be employed concurrently to alleviate various aspects age-related physiological decline. / Thesis / Doctor of Philosophy (PhD) / Aging is associated with a variety of deleterious physiological changes including loss of skeletal muscle mass and strength, reduced aerobic fitness, dyslipidemia, impaired glycemic control, and increased systemic inflammation. Broadly, this thesis explores how multiple exercise modalities and nutritional supplements can be used in combination to simultaneously alleviate several of these negative aspects of aging. This series of studies demonstrates that, in older men, consumption of a multi-ingredient nutritional supplement containing whey protein, creatine, vitamin D, calcium, and fish oil: A) stimulates significant improvements in lean mass, strength, plasma lipids, and systemic inflammation over a relatively short period of time (6 weeks) in the absence of exercise training; and B) enhances exercise training-induced gains in strength and glycemic control, as well as reductions in systemic inflammation. The findings of this thesis challenge the relatively common practice of targeting individual facets of aging with singular exercise or nutrition interventions.

Le déficit en transporteur de la créatine est une maladie rare neurologique dans laquelle la perte de fonctionnalité du transporteur de la créatine (SLC6A8) conduit à une absence de créatine au niveau cérébral et à des retards de développement majeurs chez les enfants. A l’heure actuelle, aucune thérapie efficace n’est disponible.Une approche thérapeutique potentielle est le développement de molécules prodrogues de la créatine plus lipophiles qui franchiront les membranes cellulaires de façon passive et la recherche d’une formulation galénique susceptible d’emmener la prodrogue vers les cellules cibles d’intérêt, les neurones. Ainsi, dans cette thèse, nous proposons une nouvelle voie de synthèse originale d’esters de la créatine à longue chaîne aliphatique. Ces composés présentent des propriétés pharmacologiques intéressantes : nous montrons qu’il existe une relation de structure-activité entre la taille de la chaîne aliphatique (et donc la lipophilie) et la capacité de la molécule à être internalisée dans les cellules endothéliales cérébrales, astrocytaires et neuronales, constituant l’unité neurovasculaire. Il ressort de nos observations expérimentales que l’ester dodécylique de créatine est le meilleur candidat médicament. De plus, après avoir été internalisé dans les fibroblastes des patients présentant un déficit fonctionnel du transporteur de la créatine, l’ester dodécylique subit une conversion par les estérases cellulaires, libérant ainsi la créatine dans le compartiment intracellulaire.La formulation galénique permettant de protéger ces esters de créatine jusqu’au cerveau repose, elle, sur la nanovectorisation, par encapsulation de l’ester dodécylique de créatine dans des NanoCapsules Lipidiques. L’avantage de cette formulation est de permettre également un ciblage actif vers la Barrière Hémato-Encéphalique, obstacle majeur dans le développement de thérapies ciblant le Système Nerveux Central. Nos observations expérimentales mettent en exergue cette double stratégie thérapeutique pour le traitement du déficit en transporteur de la créatine.Ce travail a été soutenu financièrement par la Fondation Lejeune. / Creatine transporter deficiency is a rare brain disease associated with the loss of function of the SLC6A8 (creatine transporter) leading to an absence of creatine at the cerebral level and to a dramatic neurodevelopmental retardation in the children. To date, no effective therapy is available.A potential therapeutic option would be the design of a pharmaceutical formulation of lipophilic prodrugs of creatine that will cross the cell membranes passively and target the neurons in order to restore the creatine content inside these cells.One of the main purposes of this dissertation is to propose an original chemistry synthesis process of creatine esters with long aliphatic chain. These compounds show interesting pharmacological properties of structure-activity relationship between the length of the aliphatic chain (i.e. lipophilicity) and the ability for the drug to enter cerebral endothelial, astroglial and neuronal cells. According to our experimental observations, the dodecyl ester creatine seems to be the best drug candidate. Moreover, the dodecyl ester is acted on by cellular esterases inside patients’ fibroblasts with a functional deficit of the SLC6A8 and increases the intracellular creatine content.The pharmaceutical formulation developed in this study consists by incorporation of dodecyl ester inside a nanovector (Lipid NanoCapsules). Two main advantages can be gained by nanovectorization: firstly, the dodecyl ester is protected from the degradation by plasmatic esterases before reaching the brain. Secondly, the nanovectorization strategy is highly valuable to brain targeting bypassing the blood-brain barrier, which remains until now a major impediment in the drug design for the Central Nervous System. Our experimental observations highlight this two-step therapeutic strategy for the treatment of deficiency of the creatine transporter.This work was financially supported by the International PhD Program of the Life Sciences division of the CEA and the Fondation Jérôme Lejeune.

Creatine is nitrogen-containing organic acid which naturally occurs in the human body. The aim of this work was to determine the optimal dose of creatine in combination with vitamin C and magnesium for male respondents aged 18-26 years. They were divided into two groups differing in the creatine dosage. Group 1 took smaller dose of creatine (3 g per day) and group 2 higher dose of creatine (10 g per day). Both groups took both magnesium and vitamin C at constant doses throughout the study. The effects of significantly different dose of creatine in the individual groups were compared with each other in terms of the performance of individuals in the powerlifting, the anthropological changes and the overal metabolism of the intakes. In all disciplines of powerlifting, group 1 recorded higher average weight gains, which were not found to be statistically significant at a significance level of alpha 0,05. Anthropological changes were measured using the InBody 160 and a diagnostic measuring tape. In both cases, group 1 recorded better results than group 2, but these results were not statistically significant at a significance level of alpha 0,05. The total metabolism of the accepted dietary supplements was investigated through analytical methods. The urine of each respondent was regularly collected and subsequently analyzed during the research. Determination of creatinine, a creatine waste product, was performed by UV-VIS spectrophotometry using the Jaffe reaction. Vitamin C was analyzed by RP-HPLC. Magnesium was determined by the ICP-OES method. After creatine suplemantion of 3 per day, group 1 showed a slight increase in creatinine in the urine, but still in the physiological range. At the significance level alpha 0,05 there was no statistically significant difference. Group 2 showed an increase above the physiological limit which was already a statistically significant difference. Overall, creatine supplementation of 3 g per day has been found as a sufficient intake of creatine needed to build up muscle mass, increase energy metabolism and overall physical performance. The metabolization itself works very well and within the physiological values.

IN ENGLISH The ischemia-reperfusion (I/R) injury, which is a consequence of myocardial infarction, represents a major cause of death worldwide. One of the most effective cardioprotective interventions increasing the resistance of hearts to the I/R injury is the adaptation to a chronic hypoxia (CH). However, the molecular mechanisms of CH are still not well understood. The most important factors responsible for the I/R injury are reactive oxygen species (ROS) produced by complexes I and III within the mitochondrial electron transport chain. Potential candidates maintaining ROS at a low level are mitochondrial creatine kinase (mtCK) and two hexokinase isoforms (HK1 and HK2). These enzymes highly support the mitochondrial oxidative phosphorylation by increasing the availability of ADP for complex V of the respiratory chain. In addition, the HK binding to mitochondria inhibits binding of the pro- apoptotic protein BAX, thereby protecting cardiac cells against apoptosis. Besides the mitochondrial CK isoform, there are two cytosolic CK (CKM and CKB) present in cardiomyocytes that help to maintain energy homeostasis. Based on the known anatomical and physiological differences between the left (LV) and the right (RV) ventricles, the first study focused on the comparing ventricles in terms of the energy...

INTRODUÇÃO: A Região Metropolitana de São Paulo é a mais populosa do Brasil. A grande frota veicular contribui para uma maior concentração de poluentes atmosféricos. Diversos poluentes podem interferir na fertilidade humana, alterando os principais parâmetros seminais. Este estudo teve como objetivo avaliar a influência dos níveis atuais de poluição atmosférica de origem veicular nos parâmetros seminais em controladores de tráfego. MÉTODOS: Foram realizadas anamnese e avaliação clínica urológica (volume testicular, presença de varicocele, criptorquidia, má formações) em 62 controladores de tráfego da CET (grupo exposto) e 210 homens comprovadamente férteis do grupo de pré-vasectomia do ambulatório da urologia do HC-FMUSP (grupo controle). Os parâmetros seminais avaliados foram concentração, motilidade (quantitativa e qualitativa), morfologia pelos critérios da OMS e critério estrito de Kruger, teste para detecção de leucócitos e testes de função espermática, CK, ROS e anticorpo anti-espermatozóide. Parâmetros hormonais também foram avaliados. Avaliação de exposição à poluição foi realizada através da dispersão de poluentes registrado pela Cetesb, gerada pelo software SURFER 8.0. RESULTADOS: Os controladores de tráfego apresentaram volume testicular maior em relação ao grupo pré-vasectomia (p<0,001). Quanto aos níveis de Estradiol (p=0,119), LH (p=0,644), FSH (p=0,140) e Testosterona total (p=0,365), ambos os grupos apresentaram valores dentro da normalidade. A concentração espermática apresentou-se homogênea nos grupos (p= 0,395); os controladores de tráfego apresentaram média de 124,9 x 106/ml e os pré-vasectomia 110,1 x 106/ml. Os controladores de tráfego apresentaram motilidade quantitativa (total) reduzida (60%) em relação aos prévasectomia (65%) (p= 0,047). A motilidade qualitativa (progressiva) também se apresentou diminuída no grupo exposto (p<0,001). As morfologias espermáticas tanto pelo critério da OMS (grupo exposto = 12%; grupo controle = 20%), quanto pelo critério estrito de Kruger (grupo exposto = 3%; grupo controle = 6%) estavam significativamente diminuídas no grupo exposto em relação ao controle (p<0,001). O marcador de maturidade Creatina Quinase apresentou-se dentro da normalidade em ambos os grupos, porém maior no grupo controle (p<0,001). Anticorpos anti-espermatozóides estavam elevados nos dois grupos, porém não foi significativo (p=0,382). Radicais livres de oxigênio apresentaram-se em altas concentrações nos dois grupos, porém não foi significativo (p=0,141). CONCLUSÕES: A análise dos dados obtidos nessa pesquisa sugere que a poluição atmosférica exerce uma influência negativa sobre os parâmetros seminais motilidade e morfologia. Causa elevação dos níveis de ROS em todos os indivíduos, indicando perda da função espermática. Ainda demonstrou-se a elevação em todos os indivíduos dos níveis de anticorpos anti-espermatozóides, sugerindo que os poluentes teriam transposto a barreira hemato-testicular. O volume testicular do grupo exposto à poluição veicular apresentar-se maior em relação ao volume testicular do grupo controle nos leva a supor que isto se deva a uma reação inflamatória aos agentes poluidores. Apesar da diferença significativa na concentração de poluentes entre os grupos, uma correlação direta com parâmetros seminais não pôde ser demonstrada / Metropolitan Region of Sao Paulo is the most populous of Brazil. The huge number of vehicles contributes for a higher concentration of air pollutants. Various pollutants can interfere in human fertility, altering the main seminal parameters. The aim of this study was to evaluate the influence of air pollution of vehicular origin on seminal parameters of traffic controllers. Clinical history and urological evaluation (testicular volume, presence of varicocele, cryptorchidism, bad formations) were carried out in 62 traffic controllers (exposed group) and 210 proven fertile men from the pre-vasectomy group of urologic clinic at Hospital of Clinics University of Sao Paulo (control group). Seminal parameters evaluated were concentration, motility (quantitative and qualitative), morphology by WHO´s criteria and Kruger´s strict criteria, test for detection of leukocytes and tests of sperm function, CK, ROS and antisperm antibody. Hormonal parameters also were evaluated. Exposition to air pollution was analyzed through the dispersion of pollutants recorded by Cetesb, generated in the software SURFER 8.0. Traffic controllers presented bigger testicular volume than prevasectomy group (p<0,001). Hormonal levels were at normal range in both groups; Estradiol (p=0,119), LH (p=0,644), FSH (p=0,140) and Total Testosterone (p=0,365). Sperm concentration was homogeneous in both groups (p= 0,395); traffic controllers presented mean of 124.9x106/ml and pre vasectomy group 110.1x106/ml. The exposed group presented quantitative (total) motility (60%) diminished than control group (65%) (p=0,047). The qualitative (progressive) motility was also diminished in the exposed group (p <0,001). The sperm morphologies as by WHO´s criteria (exposed group = 12%; control group = 20%), as by Kruger´s strict criteria (exposed group = 3%; control group = 6%) were significantly diminished in the exposed group (p<0,001). The sperm maturity marker Creatine Kinase was at normal range at both groups, but higher in the control one (p<0,001). Antisperm antibodies was elevated in both groups, however it was not significant (p=0,382). ROS presented higher concentrations in both groups, however it was not significant (p=0,141). The facts presented in this study suggest that air pollution exercises negative effects on the seminal parameters motility and morphology. It causes elevation of ROS levels in all individuals, indicating loss of sperm function. It also showed, elevation of antisperm antibodies levels, suggesting that pollutants would have transposed the blood-testis barrier. The testicular volume in the exposed group was higher than the testicular volume of the control group; we can suppose that it must occur due to an inflammatory reaction against the polluting agents. Although the significant difference in pollutants concentrations between groups, no direct correlation to seminal parameters could be demonstrated

Este estudo compara quatro diferentes intensidades com o volume total similar no exercício supino. Avaliou-se a dor muscular de início tardio (DMIT), atividade de creatina quinase (CK), as concentrações sangüíneas de interleucina (IL)-1<font face=\"symbol\">b, IL-6, fator de necrose tumoral-<font face=\"symbol\">a (TNF-<font face=\"symbol\">a), prostaglandina E2 (PGE2) e o perfil hormonal. A amostra foi composta de soldados do exército brasileiro, divididos em cinco grupos: 50%-1RM, 75%-1RM, 90%-1RM, 110%-1RM e o controle. A DMIT e a atividade plasmática de CK aumentaram significativamente (P<0,05) após a sessão de exercício. A concentração de PGE2 também teve aumento significativo (P<0,05) após a sessão (P<0,05). A concentração plasmática de cortisol após 1h do término do exercício aumentou apenas no grupo 75%-1RM (p < 0,05). Esses resultados sugerem que a intensidade no exercício supino não afeta a magnitude da DMIT, marcadores de lesão muscular, inflamação e na resposta hormonal geral, desde que haja a equalização do volume total, com exceção da concentração plasmática do cortisol, grupo 75%-1RM. / This study compared four different intensities with similar total volume of a bench press exercise for muscle soreness, creatine kinase (CK) activity, interleukin (IL)-1<font face=\"symbol\">b, IL-6, tumor necrosis factor-<font face=\"symbol\">a (TNF-<font face=\"symbol\">a), prostaglandin E2 (PGE2) and hormonal concentrations in the blood. Brazilian Army male soldiers were placed into five groups: 50%-1RM, 75%-1RM, 90%-1RM, and 110%-1RM, and control that did not perform the exercise. Muscle soreness and plasma CK activity increased significantly (p<0.05) after exercise. Serum PGE2 concentration also increased significantly (p<0.05) after exercise. After one hour post exercise cortisol increased in 75%-1RM group, with this response also exceeding the other intensities (p<0.05). These results suggest that the intensity of bench press exercise does not affect the magnitude of muscle soreness and blood markers of muscle damage, inflammation and largely similar hormonal responses, which may be attributed to the equalization of total volume, exception made for the 75%-1RM group for serum cortisol concentration.

A redução nos níveis de atividade física nos últimos tempos, devido ao aumento do uso de novas tecnologias e a vida sedentária, agregada ao consumo excessivo de alimentos, tem promovido uma epidemia de obesidade e doenças metabólicas. No contraponto deste caminho, está a realização de exercícios físicos. O exercício intervalado surge como uma boa opção para a obtenção de bons resultados físicos, principalmente, quando as pessoas possuem um tempo reduzido para a realização do seu treinamento. Muitos esportes como futebol, vôlei, tênis e atletismo, assim como o exercício intervalado, necessitam de indivíduos que possam competir, ou simplesmente praticar, várias vezes dentro de um intervalo de poucos dias. Atletas profissionais ou amadores treinam quase todos os dias e necessitam de uma intervenção dietética para manter o seu nível de energia estável para a realização de treinos e partidas, fazendo uso frequente de suplementos alimentares. Dentro desta gama de suplementos alimentares a Creatina é um dos mais utilizados coadjuvantes na melhoria do desempenho atlético, demonstrando potencial aumento de força, bem como aumento de massa magra, o que pode estar relacionado com o sistema do fator de Crescimento semelhante à insulina 1 (IGF-1) ou o seu receptor celular o IGF-1R. O objetivo deste trabalho foi analisar o impacto da suplementação de Creatina juntamente com o treinamento intervalado de alta intensidade na expressão proteica de IGF-1R no tecido muscular, além de analisar as concentrações sanguíneas de lactato e glicemia, avaliar o desempenho ou a performance, dos ratos antes e após o treinamento intervalado e verificar o ganho de peso dos animais nos diferentes grupos. Trinta e sete (37) ratos Wistar machos com 75 dias no começo do experimento foram randomizados e separados em três grupos: A (Treinado sem suplementação, 13 animais), B (Treinado suplementado com Creatina e Carboidrato, 12 animais) e C (Treinado suplementado com Creatina, 12 animais). O protocolo de treinamento consistiu em 1 minuto de exercício a 110% da velocidade de fadiga do teste máximo em esteira, seguidos por 30 segundos a 40% desta, totalizando 30 min, cinco vezes por semana durante trinta e dois dias corridos. A suplementação de Creatina ocorreu durante todo o período de treinamento, duas horas antes do exercício. A água foi utilizada como veículo de infusão nos grupos A e C e uma solução de glicose a 10% no grupo B. Como resultado foi verificada uma melhoria no desempenho físico dos ratos em todos os grupos. Bem como uma maior expressão proteica do IGF-1R nos grupos treinados suplementados (B e C) quando comparados ao grupo treinado sem suplementação (A). Já os dados de glicemia, lactato e ganho de massa não apresentaram diferença significativa entre os grupos. Conclui-se que o treinamento intervalado de alta intensidade se apresenta como uma boa opção para melhorias na performance física, e que a suplementação de Creatina está envolvida no aumento da expressão proteica do IGF-1R. Contudo o protocolo de treinamento e suplementação utilizados no estudo não se refletiram em diferenças nas análises glicemia, lactato e massa dos animais. / The reduction in levels of physical activity in recent times, due to the increased use of new technologies and sedentary life, added to the excessive consumption of food, has promoted an epidemic of obesity and metabolic diseases. In contrast this way, is physical exercises. The interval exercise appears as a good option for getting good physical results, mainly, when people don’t have enough time to do their training. Many sports such as football, volleyball, tennis and athletics, as well as the interval exercise, require athletes to compete, or simply practicing several times within a few days. These professional or amateur athletes train almost every day and need a dietary intervention to keep your energy level stable for training and matches appropriately, making use often, dietary supplements. Within this range of dietary supplements, Creatine is one of the most used resource for improving athletic performance, demonstrating increased strength and power, as well as increased lean mass, which may be related to the insulin-like growth factor 1 (IGF-1) system or its cellular receptor IGF-1R. The aim of this study was to analyze the impact of creatine supplementation along with high intensity interval training on protein expression of IGF-1R in muscle tissue, and analyzing blood concentrations of lactate and glucose, evaluate the performance of rats before and after interval training, examine the weight gain of the animals in different groups. Thirty-seven (37) male Wistar rats at 75 days at the beginning of the experiment were randomly divided into three groups: A (Trained without supplementation, 13 animals), B (Trained supplemented with creatine and Carbohydrate, 12 animals) and C (Trained supplemented with creatine, 12 animals). The training protocol consisted of a 1 minute to 110% of the test speed of fatigue, followed by 30 seconds at 40% of this, totaling 30 minutes, five times a week for consecutive thirty-two days. The creatine supplementation occurred throughout the training period, two hours before the exercise, with water as a vehicle for infusion in groups A and C, and 10% glucose solution in group B. As a result we had improvement in physical performance of rats in all groups. As well as increased protein expression of IGF-1R in groups trained supplemented (B and C) when compared to the trained group without supplementation (A). Meanwhile, data from the glucose, lactate and mass gain did not differ significantly between groups. It is concluded that high-intensity interval training is presented as a good option to improve physical performance, and that creatine supplementation is involved in the increased protein expression of IGF-1R. The training and supplementation protocol used in the study were not reflected in differences in the analysis of IGF-1R, glucose, lactate and gain mass in the animals.

Divers stimuli tels que l'ischémie, l'hypoxie et l'exercice peuvent induire la déplétion en ATP provoquant une déregulation de l'homéostasie énergétique. Cependant, les cellules disposant de mécanismes compensatoires pour contrebalancer et compenser le déficit de l'état énergétique cellulaire. Deux enzymes clés participent à la régulation du métabolisme énergétique cellulaire. La créatine kinase (CK) peut réagir immédiatement comme transporteur d'énergie. D'autre part la protéine kinase activée par l'AMP (AMPK), régule au niveau cellulaire et du corps en entier la livraison et la consommation d'énergie. Dans ce travail de thèse, les outils de base pour realiser un criblage des cibles de l'AMPK ont d'abord été mis en place. Ce sont les protocoles multidimensionnelles pour la purification de protéines par HPLC et le criblage in vitro de cibles membranaires de l'AMPK, dont le sous-fractionnement des membranes et la separation par électrophorèse de type blue native PAGE. Différents candidats potentiels de l'AMPK ont été obtenus, et deux ont été confirmés par phosphorylation in vitro. Ensuite, une interaction entre les deux enzymes, l'AMPK et la CK, a été confirmée pour la première fois in vitro et in vivo. L'AMPK phosphoryle la créatine kinase cytosolique du cerveau (BCK) sur la serine 6 in vitro et in vivo. Cette phosphorylation a été mis en evidance à l'aide de tests de phosphorylation et d'un anticorps généré spécifique de la phospho-Ser6. Le system de double hybride en levure a montré que cette phosphorylation est acompagné par une interaction transitoire impliquant spécifiquement l'AMPK active et BCK non phosphorylé. La phosphorylation médiée par AMPK n'affecte pas l'activité enzymatique de BCK mais localise la kinase dans le réticulum endoplasmique (RE) in vivo. Le travail presente dans ce manuscript confirme une interaction entre les deux enzymes clefs dans l'homeostasis energetique. La caracherization in vitro et in vivo de la phosphorylation de la BCK par l'AMPK suggère que l'AMPK regule probablement l'associattion de BCK aux compartements subcellulaires et pas l'activité enzymatique. Cette localisation est induite par l'AMPK en cas de stress énergetique et peut soutenir des processus fortement dépendant de l'ATP dans ce microenvironnement, comme par exemple le pompage de calcium.