AMP-Activated Protein Kinase (AMPK) Mediates Nutrient Regulation of Thioredoxin-Interacting Protein (TXNIP) in Pancreatic Beta-Cells

Thioredoxin-interacting protein (TXNIP) regulates critical biological processes including inflammation, stress and apoptosis. TXNIP is upregulated by glucose and is a critical mediator of hyperglycemia-induced beta-cell apoptosis in diabetes. In contrast, the saturated long-chain fatty acid palmitate, although toxic to the beta-cell, inhibits TXNIP expression. The mechanisms involved in the opposing effects of glucose and fatty acids on TXNIP expression are unknown. We found that both palmitate and oleate inhibited TXNIP in a rat beta-cell line and islets. Palmitate inhibition of TXNIP was independent of fatty acid beta-oxidation or esterification. AMP-activated protein kinase (AMPK) has an important role in cellular energy sensing and control of metabolic homeostasis; therefore we investigated its involvement in nutrient regulation of TXNIP. As expected, glucose inhibited whereas palmitate stimulated AMPK. Pharmacologic activators of AMPK mimicked fatty acids by inhibiting TXNIP. AMPK knockdown increased TXNIP expression in presence of high glucose with and without palmitate, indicating that nutrient (glucose and fatty acids) effects on TXNIP are mediated in part via modulation of AMPK activity. TXNIP is transcriptionally regulated by carbohydrate response element-binding protein (ChREBP). Palmitate inhibited glucose-stimulated ChREBP nuclear entry and recruitment to the Txnip promoter, thereby inhibiting Txnip transcription. We conclude that AMPK is an important regulator of Txnip transcription via modulation of ChREBP activity. The divergent effects of glucose and fatty acids on TXNIP expression result in part from their opposing effects on AMPK activity. In light of the important role of TXNIP in beta-cell apoptosis, its inhibition by fatty acids can be regarded as an adaptive/protective response to glucolipotoxicity. The finding that AMPK mediates nutrient regulation of TXNIP may have important implications for the pathophysiology and treatment of diabetes

Subcellular trafficking of the substrate transporters GLUT4 and CD36 in cardiomyocytes

Cardiomyocytes use glucose as well as fatty acids for ATP production. These substrates are transported into the cell by glucose transporter 4 (GLUT4) and the fatty acid transporter CD36. Besides being located at the sarcolemma, GLUT4 and CD36 are stored in intracellular compartments. Raised plasma insulin concentrations and increased cardiac work will stimulate GLUT4 as well as CD36 to translocate to the sarcolemma. As so far studied, signaling pathways that regulate GLUT4 translocation similarly affect CD36 translocation. During the development of insulin resistance and type 2 diabetes, CD36 becomes permanently localized at the sarcolemma, whereas GLUT4 internalizes. This juxtaposed positioning of GLUT4 and CD36 is important for aberrant substrate uptake in the diabetic heart: chronically increased fatty acid uptake at the expense of glucose. To explain the differences in subcellular localization of GLUT4 and CD36 in type 2 diabetes, recent research has focused on the role of proteins involved in trafficking of cargo between subcellular compartments. Several of these proteins appear to be similarly involved in both GLUT4 and CD36 translocation. Others, however, have different roles in either GLUT4 or CD36 translocation. These trafficking components, which are differently involved in GLUT4 or CD36 translocation, may be considered novel targets for the development of therapies to restore the imbalanced substrate utilization that occurs in obesity, insulin resistance and diabetic cardiomyopathy

Arabidopsis thaliana tolerates iron deficiency more than Thellungiella salsuginea by inducing metabolic changes at the root level

Several studies have used A. thaliana as a model to identify the physiological and molecular mechanisms underlying iron deficiency tolerance in plants. Here, Arabidopsis thaliana and Thellungiella salsuginea were used to investigate the differential responses to iron deficiency of these two species. Plants were cultivated in hydroponic medium containing 5 or 0 μM Fe, for 10 days. Results showed that rosette biomass was more reduced in T. salsuginea than in A. thaliana when grown on Fe-deficient medium. As a marker for iron deficiency tolerance, the induction of ferric chelate reductase (FCR) and phosphoenolpyruvate carboxylase (PEPC) activities was observed only in A. thaliana roots. In addition, we found that the accumulation of phenolic acids in roots of N1438 ecotype of A. thaliana was stimulated by Fe deficiency. Furthermore, an increase of flavonoids content in the root and exudates was observed under Fe-deficiency in this ecotype. Unlike other abiotic stresses, it appears that iron deficiency effects were more pronounced in Thellungiella than in Arabidopsis. The higher tolerance of the Arabidopsis plant to iron deficiency may be due to the metabolic changes occurring in the roots

Association épisodique d'halophytes stricts et de glycophytes dans un écosystème hydromorphe salé en zone semi-aride

La production de biomasse et le prélèvement d'éléments nutritifs majeurs (N, P, K) dans une parcelle mise hors pâturage en bordure de la sebkha d'Enfidha (100 km au sud de Tunis, étage bioclimatique semi-aride inférieur) ont été suivis au cours de 2 années consécutives, l'une particulièrement sèche et l'autre relativement pluvieuse. Environ la moitié de la biomasse aérienne sur la parcelle correspond à des halophytes pérennes caractéristiques de sols à forte salinité. Au cours de l'année pluvieuse, 40% de la production primaire de l'écosystème sont dus aux espèces annuelles, parmi lesquelles Medicago ciliaris (L) Krock, M polymorpha L, M truncatula Gaertn, et M minima Grufb sont dominantes. La réaction de ces Medicago au stress salin a été étudiée au laboratoire. Au stade végétatif, la production de MS est restreinte par NaCI (110 mM et 160 mM) chez tous les Medicago. Cet effet est lié à une réduction de la surface foliaire plutôt qu'à une baisse de la vitesse d'assimilation nette. Le sel diminue la production de graines en limitant le nombre de gousses, sans affecter le nombre de graines par gousse ni le poids individuel de la graine. La viabilité des graines n'est que très faiblement affectée. En dépit de leur origine (bordure de sebkha peuplée d'halophytes), les Medicago se sont révélés relativement sensibles à la salinité. La dynamique de leur reproduction dépend du maintien de la salinité à un niveau faible. Ces résultats suggèrent que ces plantes exploitent un horizon superficiel moins salé que celui qui supporte la croissance des halophytes. La présence des halophytes pourrait favoriser le maintien d'un horizon peu salé et relativement fertile, occupé périodiquement par les Medicago annuels.Episodic association of strict halophytes and glycophytes in a saline, hydromorphic ecosystem in semi-arid zones. The biomass production and the uptake of mineral nutrients (N, P, K) in an ungrazed area edging the sebkha of Enfidha (100 km south-east of Tunis; semi-arid bioclimatic zone) were studied for 2 successive years; the first year was particularly dry, the second relatively rainy. Half the aerial biomass was produced by perennial halophytes. Annual plants were responsible for a large part of the ecosystem productivity in the second year. Among them, Medicago ciliaris (L) Krock, M polymorpha L, M truncatula Gaertn and M minima Grufb were the dominant species (40% of ecosystem primary production). We studied their response to salinity in controlled culture conditions. Vegetative growth (dry matter production) was reduced by NaCl (110 or 160 mM) in all Medicago species. This effect was related to a reduction in leaf area rather than in assimilation efficiency. The number of seeds produced per plant and per unit biomass was severely reduced in the presence of salt. In contrast, individual seed weight, as well as their germinating power, were only weakly affected. In spite of their origin (edge of sebkha crowded by halophytes), the Medicago species studied appeared to be glycophytic, on the basis of their growth and nutritional responses to NaCl. Their reproduction depended on the maintenance of the salt concentration at low levels. These results suggest that these plants exploit the upper horizon layer, which is less salty than the deeper ones, which support the halophytes. The presence of halophytes might contribute to maintaining a fertile and less salty superficial layer, occupied periodically by annual Medicago species

Effect of salinity on germination, phytase activity and phytate content in lettuce seedling

Publication Inra prise en compte dans l'analyse bibliométrique des publications scientifiques mondiales sur les Fruits, les Légumes et la Pomme de terre. Période 2000-2012. http://prodinra.inra.fr/record/256699International audienceSeeds of four lettuce (Lactuca sativa L.) varieties (Romaine, Augusta, Vista and Verte) differing in their salt sensitivity were sown at 0 (Control), 50, 100 and 150 mM NaCl. The final germination percentage decreased with the increasing salinity and was annulated at the highest salt concentration in Vista and Verte, the most sensitive varieties. However, in the less sensitive ones, Romaine and Augusta, it was slightly modified at 50 and 100 mM NaCl and then decreased by 50% compared with the control, at 150 mM. The effects of NaCl 100 mM on seedling growth, phytase activities, phytate and inorganic phosphorus contents were studied in Romaine and Vista showing different behaviours towards salinity. Radicle and hypocotyl length and fresh and dry weights were reduced by salt treatment in both varieties. In addition, radicle phytase activity exhibited an increase in Romaine (less sensitive) and a decrease in Vista (more sensitive). In hypocotyl, this activity showed no difference with the control in the two varieties. However, in cotyledons, and during early hours after germination, salinity decreased phytase activity in both varieties whereas in the later hours (72-96 h) this activity reached the value of the control in Romaine. The enhancement of phytase activity was concomitant with an increase in orthophosphate content and a decrease in phytate reserve. These results suggest that salt presence in the medium delays Pi remobilization from phytate stock, but stimulates assimilation of phosphorus more than its accumulation in the organs of the two lettuce varieties

Comprehension and hydrogeological conceptualization of aquifer in arid and semi-arid regions using integrated hydrogeological information system : case of the deep aquifer of Zéramdine-Béni Hassen (east-central Tunisia)

In arid and semi-arid regions, the groundwater overexploitation caused drawdown in piezometric levels and a degradation of chemical water quality. That is why the groundwater monitoring needs a good comprehension of the hydrogeological aquifer properties. This is specially the case of Z,ramdine-B,ni Hassen deep aquifer (east-central Tunisia). Seismic profiles interpretation highlights the existence of the Z,ramdine fault corridor, the BoumerdSs anticline, the Moknine and Mahdia grabens that represent lateral boundaries for the study aquifer. The outcrop of the aquifer is located in the Z,ramdine, B,ni Hassen and Ain Ben Jannet regions, where two lithostratigraphic sections were realized. The piezometric study shows that the principal groundwater flow is from west to east. A secondary flow is from NW to SE. The hydrochemical study of 22 sample shows that the aquifer is characterized by freshwater, dominated by Na-Ca-Cl-SO4 facies. The salinity increase is from the west to the east, which coincides with the principal water flow direction. The integration of all results deduced from the hydrogeophysic, hydrodynamic and hydrochemical studies is developed to investigate hydrological processes of Z,ramdine-B,ni Hassen aquifer and consequently to propose a conceptual model, which will help to propose a rescue plan for the studied aquifer and to implement a spatial hydrogeological database using the global information system and then to characterize the complex aquifer system

Implementation of a 3-D groundwater flow model in a semi-arid region using MODFLOW and GIS tools : The Zeramdine-Beni Hassen Miocene aquifer system (east-central Tunisia)

In this work, an integrated methodology was developed to investigate hydrological processes in Zeramdine-Beni Hassen Miocene aquifer and to validate the groundwater proprieties deduced from the geological, geophysical, hydrodynamic and hydrochemical studies done in the region, using the coupling of groundwater flow model MODFLOW 2000 code with Geographic Information System tools. A 3-D groundwater flow model was developed for this aquifer using a large amount of available geological and hydrological data. The groundwater flow model was calibrated and validated with datasets during the 1980-2007 period. The results show that the ZBH aquifer exhibits the highest sensibility to changes of water infiltration and hydraulic conductivity. The model simulation shows a good degree of understand to the aquifer hydrogeology. The model can be regarded as a useful tool for analyzing the hydrological processes for complex groundwater that have similar geological and hydrogeological conditions and will help to propose a management rescue plan for the studied aquifer, especially for aquifer characterization in arid and semi arid regions

Antioxidative responses of Ocimum basilicum to sodium chloride or sodium sulphate salinization

Soils and ground water in nature are dominated by chloride and sulphate salts. There have been several studies concerning NaCl salinity, however, little is known about the Na2SO4 one. The effects on antioxidative activities of chloride or sodium sulphate in terms of the same Naþ equivalents (25 mM Na2SO4 and 50 mM NaCl) were studied on 30 day-old plants of Ocimum basilicum L., variety Genovese subjected to 15 and 30 days of treatment. Growth, thiobarbituric acid reactive substances (TBARS), relative ion leakage ratio (RLR), hydrogen peroxide (H2O2), ascorbate and glutathione contents as well as the activities of ascorbate peroxidase (APX, EC 1.11.1.11); glutathione reductase (GR, EC 1.6.4.2) and peroxidases (POD, EC 1.11.1.7) were determined. In leaves, growth was more depressed by 25 mM Na2SO4 than 50 mM NaCl. The higher sensitivity of basil to Na2SO4 was associated with an enhanced accumulation of H2O2, an inhibition of APX, GR and POD activities (with the exception of POD under the 30-day-treatment) and a lower regeneration of reduced ascorbate (AsA) and reduced glutathione (GSH). However, the changes in the antioxidant metabolism were enough to limit oxidative damage, explaining the fact that RLR and TBARS levels were unchanged under both Na2SO4 and NaCl treatment. Moreover, for both salts the 30-day-treatment reduced H2O2 accumulation, unchanged RLR and TBARS levels, and enhanced the levels of antioxidants and antioxidative enzymes, thus achieving an adaptation mechanism against reactive oxygen species

Characterizing a complex aquifer system using geophysics, hydrodynamics and geochemistry : a new distribution of Miocene aquifers in the Zeramdine and Mahdia-Jebeniana blocks (east-central Tunisia)

The Zeramdine and Mandia-jebeniana blocks are located in the Sahel region in east-central Tunisia. Active tectonics have divided the region into numerous sub-units, as result of multiple phases of distension and compression. The Miocene fluvio-deltaic sediment sandy layers have aquiferous capacities but their hydraulic properties are still unknown, due to the lack of investigation wells. This study proposes a new description of the regional hydrogeology of Miocene deposits. Seismic-reflection and wireline logging of petroleum and water wells were used to understand the structure and the geometry of the Miocene reservoirs. The groundwater flow and its relationship to the sedimentary and tectonic context were then identified by studying piezometry and hydrochemistry. Two Miocene deep aquifer systems were identified: (1) Zeramdine-Beni Hassen to the north and (2) Jebeniana-Ksour Essef to the south. These aquifers are separated by the Mandia graben. Other major tectonic structures, such as the Zeramdine fault corridor, the Moknine graben, and the El-jem half-graben represent lateral boundaries for these aquifers. Other deeper sandy and clayey-sandy reservoirs were also identified in the area. Their repartition, thickness and depth vary from one block to other. Hydrodynamics of the deep aquifers seems to be controlled by geological structures. Two independent compartments were identified: in the northern block groundwater flows from West to East and from Northwest to Southeast, while in the southern block it flows from Northwest to Southeast. Geochemical facies are of two types: Na-Ca-Cl-SO4 for the Zeramdine-Beni Hassen deep aquifer and Na-Cl for the jebeniana-Ksour Essef deep aquifer. The hydrodynamic and geochemical results confirm the sharing of the Miocene sediments into two aquifers