Low-affinity Transport System Research Articles

Induction of nitrate uptake in Sauvignon Blanc and Chardonnay grapevines depends on the scion and is affected by the rootstock

Background and Aims Nitrate is a major form of inorganic nitrogen present in cultivated soils; however, information on the mechanisms responsible for uptake of the anion in grapevines is scarce. Methods and Results The response to external nitrate was studied in two clones of the cultivars Chardonnay and Sauvignon Blanc. Grapevines, own-rooted or grafted on the two rootstocks SO4 and K5BB, were grown in nutrient solution and, after a period of nitrogen (N)-deprivation, exposed to 0.2 or 1 mmol/L nitrate. The uptake was an inducible process, operated by high- and low-affinity transport systems. The magnitude and time dependence of the induction varied as a function of the clone. Uptake rate as a function of nitrate external concentration showed a multiphasic pattern. Although nitrate exposure caused a transient up-regulation of nitrate influx transporter genes, a clear correlation with the rise in nitrate uptake could not be found; in contrast, a negative relationship between changes in uptake rates and expression of a nitrate efflux transporter gene was observed. Conclusions In the grapevine, the response of low- and high-affinity transport systems to external nitrate was favoured by the presence of the rootstock and also dependent on the characteristics of the scion. Low-affinity uptake and efflux from root cells conceivably play an important role in the overall N-nitrate acquisition. Significance of the Study This study shows that activation of mechanisms involved in nitrate uptake in the grapevine is strongly affected by the scion–rootstock combination. Results may be significant for developing agronomic practices and selection programmes related to nitrogen use in the grapevine.

The influence of shoot and root size on nitrogen uptake in wheat is affected by nitrate affinity in the roots during early growth

Shoot and root system size influences N uptake in wheat (Triticum aestivum L.). Previously, we showed that four wheat genotypes with different biomass had similar N uptake at tillering. In the present study, we determined whether the similarity in N uptake in these genotypes was associated with genotypic differences in the affinity of the root system for NO3- uptake. Kinetic parameters of NO3- uptake were measured in hydroponic seedlings of vigorous and nonvigorous early growth wheat genotypes by exposing them to solutions with differing concentrations of K15NO3 for 15min. In the low concentration range, the high-affinity transport system of the nonvigorous cultivar Janz showed a higher maximum influx rate than the three vigorous lines and a higher affinity than two of the three vigorous lines. At high NO3- concentrations, where the low-affinity transport system was functional, the responsiveness of NO3- uptake to external concentrations was greater in Janz than in the vigorous lines. Both the high- and low-affinity transport systems were inducible. The genotypic variation in the kinetic parameters of NO3- uptake was large enough to offset differences in morphological traits and should be considered in efforts to improve N uptake. In a field trial, the growth and N uptake performance of the four wheat genotypes was investigated over the winter-spring growing season (June-November of 2010). The field trial showed that although early N uptake was disproportionately large relative to biomass accumulation, the differences in uptake at tillering can be changed by subsequent patterns of uptake.

The nitrate transporter MtNPF6.8 (MtNRT1.3) transports abscisic acid and mediates nitrate regulation of primary root growth in Medicago truncatula.

Elongation of the primary root during postgermination of Medicago truncatula seedlings is a multigenic trait that is responsive to exogenous nitrate. A quantitative genetic approach suggested the involvement of the nitrate transporter MtNPF6.8 (for Medicago truncatula NITRATE TRANSPORTER1/PEPTIDE TRANSPORTER Family6.8) in the inhibition of primary root elongation by high exogenous nitrate. In this study, the inhibitory effect of nitrate on primary root elongation, via inhibition of elongation of root cortical cells, was abolished in npf6.8 knockdown lines. Accordingly, we propose that MtNPF6.8 mediates nitrate inhibitory effects on primary root growth in M. truncatula. pMtNPF6.8:GUS promoter-reporter gene fusion in Agrobacterium rhizogenes-generated transgenic roots showed the expression of MtNPF6.8 in the pericycle region of primary roots and lateral roots, and in lateral root primordia and tips. MtNPF6.8 expression was insensitive to auxin and was stimulated by abscisic acid (ABA), which restored the inhibitory effect of nitrate in npf6.8 knockdown lines. It is then proposed that ABA acts downstream of MtNPF6.8 in this nitrate signaling pathway. Furthermore, MtNPF6.8 was shown to transport ABA in Xenopus spp. oocytes, suggesting an additional role of MtNPF6.8 in ABA root-to-shoot translocation. (15)NO3(-)-influx experiments showed that only the inducible component of the low-affinity transport system was affected in npf6.8 knockdown lines. This indicates that MtNPF6.8 is a major contributor to the inducible component of the low-affinity transport system. The short-term induction by nitrate of the expression of Nitrate Reductase1 (NR1) and NR2 (genes that encode two nitrate reductase isoforms) was greatly reduced in the npf6.8 knockdown lines, supporting a role of MtNPF6.8 in the primary nitrate response in M. truncatula.

Nickel and zinc isotope fractionation in hyperaccumulating and nonaccumulating plants.

Until now, there has been little data on the isotope fractionation of nickel (Ni) in higher plants and how this can be affected by plant Ni and zinc (Zn) homeostasis. A hydroponic cultivation was conducted to investigate the isotope fractionation of Ni and Zn during plant uptake and translocation processes. The nonaccumulator Thlaspi arvense, the Ni hyperaccumulator Alyssum murale and the Ni and Zn hyperaccumulator Noccaea caerulescens were grown in low (2 μM) and high (50 μM) Ni and Zn solutions. Results showed that plants were inclined to absorb light Ni isotopes, presumably due to the functioning of low-affinity transport systems across root cell membrane. The Ni isotope fractionation between plant and solution was greater in the hyperaccumulators grown in low Zn treatments (Δ(60)Ni(plant-solution) = -0.90 to -0.63‰) than that in the nonaccumulator T. arvense (Δ(60)Ni(plant-solution) = -0.21‰), thus indicating a greater permeability of the low-affinity transport system in hyperaccumulators. Light isotope enrichment of Zn was observed in most of the plants (Δ(66)Zn(plant-solution) = -0.23 to -0.10‰), but to a lesser extent than for Ni. The rapid uptake of Zn on the root surfaces caused concentration gradients, which induced ion diffusion in the rhizosphere and could result in light Zn isotope enrichment in the hyperaccumulator N. caerulescens. In high Zn treatment, Zn could compete with Ni during the uptake process, which reduced Ni concentration in plants and decreased the extent of Ni isotope fractionation (Δ(60)Ni(plant-solution) = -0.11 to -0.07‰), indicating that plants might take up Ni through a low-affinity transport system of Zn. We propose that isotope composition analysis for transition elements could become an empirical tool to study plant physiological processes.

Effects of magnesium deficiency on magnesium uptake activity of rice root, evaluated using 28 Mg as a tracer

The mechanisms underlying magnesium (Mg) uptake by plant roots remain to be fully elucidated. In particular, there is little information about the effects of Mg deficiency on Mg uptake activity. A Mg uptake kinetic study is essential for better understanding the Mg uptake system. We performed a Mg uptake tracer experiment in rice plants using 28 Mg. Mg uptake was mediated by high- and low-affinity transport systems. The K m value of the high-affinity transport system was approximately 70 μM under Mg-deficient conditions. The Mg uptake activity was promoted by Mg deficiency, which in turn fell to the basal level after 5- min of Mg resupply. The induced uptake rate was inhibited by ionophore treatment, suggesting that an energy-dependent uptake system is enhanced by Mg deficiency. The Mg uptake changes rapidly with Mg conditions in rice, as revealed by a 28 Mg tracer experiment. This technique is expected to be applicable for Mg uptake analyses, particularly in mutants or other lines.

Copper tolerance mediated by polyphosphate degradation and low-affinity inorganic phosphate transport system in Escherichia coli

BackgroundMetal tolerance in bacteria has been related to polyP in a model in which heavy metals stimulate the polymer hydrolysis, forming metal-phosphate complexes that are exported. As previously described in our laboratory, Escherichia coli cells grown in media containing a phosphate concentration >37 mM maintained an unusually high polyphosphate (polyP) level in stationary phase. The aim of the present work was to evaluate the influence of polyP levels as the involvement of low-affinity inorganic phosphate transport (Pit) system in E. coli copper tolerance.ResultsPolyP levels were modulated by the media phosphate concentration and/or using mutants in polyP metabolism. Stationary phase wild-type cells grown in high phosphate medium were significantly more tolerant to copper than those grown in sufficient phosphate medium. Copper addition to tolerant cells induced polyP degradation by PPX (an exopolyphosphatase), phosphate efflux and membrane polarization. ppk−ppx− (unable to synthesize/degrade polyP), ppx− (unable to degrade polyP) and Pit system mutants were highly sensitive to metal even in high phosphate media. In exponential phase, CopA and polyP-Pit system would act simultaneously to detoxify the metal or one could be sufficient to safeguard the absence of the other.ConclusionsOur results support a mechanism for copper detoxification in exponential and stationary phases of E. coli, involving Pit system and degradation of polyP. Data reflect the importance of the environmental phosphate concentration in the regulation of the microbial physiological state.

Functional analysis of [methyl-3H]choline uptake in glioblastoma cells: Influence of anti-cancer and central nervous system drugs

Positron emission tomography (PET) and PET/computed tomography (PET-CT) studies with 11C- or 18F-labeled choline derivatives are used for PET imaging in glioblastoma patients. However, the nature of the choline transport system in glioblastoma is poorly understood. In this study, we performed a functional characterization of [methyl-3H]choline uptake and sought to identify the transporters that mediate choline uptake in the human glioblastoma cell lines A-172 and U-251MG. In addition, we examined the influence of anti-cancer drugs and central nervous system drugs on the transport of [methyl-3H]choline. High- and low-affinity choline transport systems were present in A-172 cells, U-251MG cells and astrocytes, and these were Na+-independent and pH-dependent. Cell viability in A-172 cells was not affected by choline deficiency. However, cell viability in U-251MG cells was significantly inhibited by choline deficiency. Both A-172 and U-251MG cells have two different choline transporters, choline transporter-like protein 1 (CTL1) and CTL2. In A-172 cells, CTL1 is predominantly expressed, whereas in U-251MG cells, CTL2 is predominantly expressed. Treatment with anti-cancer drugs such as cisplatin, etoposide and vincristine influenced [methyl-3H]choline uptake in U-251MG cells, but not A-172 cells. Central nervous system drugs such as imipramine, fluvoxamine, paroxetine, reboxetine, citalopram and donepezil did not affect cell viability or [methyl-3H]choline uptake. The data presented here suggest that CTL1 and CTL2 are functionally expressed in A-172 and U-251MG cells and are responsible for [methyl-3H]choline uptake that relies on a directed H+ gradient as a driving force. Furthermore, while anti-cancer drugs altered [methyl-3H]choline uptake, central nervous system drugs did not affect [methyl-3H]choline uptake.

An Emerging Protagonist: Sodium Glucose Co-transporters (SGLTs) as a Burgeoning Target for the Treatment of Diabetes Mellitus

Contemporary therapies to rationalize the hyperglycaemia in type 2 diabetes mellitus (T2DM) generally involve insulin-dependent mechanisms and lose their effectiveness as pancreatic b-cell function decreases to a greater extent. Kidney emerges out as a novel and potential target to trim down the complications of T2DM. The filtered glucose is reabsorbed principally through the sodium glucose co-transporter-2 (SGLT2), a low affinity transport system, which are present at the luminal surface cells that covers the first segment of proximal tubules. Competitive inhibition of SGLT2 therefore represents an innovative therapeutic strategy for the treatment of hyperglycaemia and/or obesity in patients with type 1 or type 2 diabetes by enhancing glucose and energy loss through the urine. Selective inhibitors of SGLT2 reduce glucose reabsorption, causing excess glucose to be eliminated in the urine; this decreases plasma glucose. SGLT2 inhibitors are coupled with osmotic dieresis and loss of weight which aid in reducing the blood pressure. The observation that individuals with familial renal glycosuria maintain normal longterm kidney function provides some encouragement that this mode of action will not adversely affect renal function. This novel mechanism of targeting kidney for the treatment of T2DM is reasonably valuable and is independent of insulin and clutch with the low risk of hypoglycemia.

Functional Properties of the Retinal Glutamate Transporters GLT-1c and EAAT5

In the mammalian retina, glutamate uptake is mediated by members of a family of glutamate transporters known as "excitatory amino acid transporters (EAATs)." Here we cloned and functionally characterized two retinal EAATs from mouse, the GLT-1/EAAT2 splice variant GLT-1c, and EAAT5. EAATs are glutamate transporters and anion-selective ion channels, and we used heterologous expression in mammalian cells, patch-clamp recordings and noise analysis to study and compare glutamate transport and anion channel properties of both EAAT isoforms. We found GLT-1c to be an effective glutamate transporter with high affinity for Na(+) and glutamate that resembles original GLT-1/EAAT2 in all tested functional aspects. EAAT5 exhibits glutamate transport rates too low to be accurately measured in our experimental system, with significantly lower affinities for Na(+) and glutamate than GLT-1c. Non-stationary noise analysis demonstrated that GLT-1c and EAAT5 also differ in single-channel current amplitudes of associated anion channels. Unitary current amplitudes of EAAT5 anion channels turned out to be approximately twice as high as single-channel amplitudes of GLT-1c. Moreover, at negative potentials open probabilities of EAAT5 anion channels were much larger than for GLT-1c. Our data illustrate unique functional properties of EAAT5, being a low-affinity and low-capacity glutamate transport system, with an anion channel optimized for anion conduction in the negative voltage range.

A reevaluation of the role of Arabidopsis NRT1.1 in high-affinity nitrate transport.

A reevaluation of flux data for Arabidopsis mutants reveals that nitrate uptake through AtNRT1.1 conforms to a single low-affinity transport system that makes virtually no contribution to high-affinity nitrate uptake.

Characterization of ammonium and nitrate uptake and assimilation in roots of tea plants

It has been pointed out that tea (Camellia sinensis (L.) O. Kuntze) prefers ammonium (NH 4 + ) over nitrate (NO 3 − ) as an inorganic nitrogen (N) source. 15N studies were conducted using hydroponically grown tea plants to clarify the characteristics of uptake and assimilation of NH 4 + and NO 3 − by tea roots. The total 15N was detected, and kinetic parameters were calculated after feeding 15NH 4 + or 15NO 3 − to tea plants. The process of N assimilation was studied by monitoring the dynamic 15N abundance in the free amino acids of tea plant roots by GC-MS. Tea plants supplied with 15NH 4 + absorbed significantly more 15N than those supplied with 15NO 3 − . The kinetics of 15NH 4 + and 15NO 3 − influx into tea plants followed a classic biphasic pattern, demonstrating the action of a high affinity transport system (HATS) and a low affinity transport system (LATS). The V max value for NH 4 + uptake was 54.5 nmol/(g dry wt min), which was higher than that observed for NO 3 − (39.3 nmol/(g dry wt min)). KM estimates were approximately 0.06 mM for NH 4 + and 0.16 mM for NO 3 − , indicating a higher rate of NH 4 + absorption by tea plant roots. Tea plants fed with 15NH 4 + accumulated larger amounts of assimilated N, especially glutamine (Gln), compared with those fed with 15NO 3 − . Gln, Glu, theanine (Thea), Ser, and Asp were the main free amino acids that were labeled with 15N under both conditions. The rate of N assimilation into Thea in the roots of NO 3 − -supplied tea plants was quicker than in NH 4 + -supplied tea plants. NO 3 − uptake by roots, rather than reduction or transport within the plant, seems to be the main factor limiting the growth of tea plants supplied with NO 3 − as the sole N source. The NH 4 + absorbed by tea plants directly, as well as that produced by NO 3 − reduction, was assimilated through the glutamine synthetase-glutamine oxoglutarate aminotransferase pathway in tea plant roots. The 15N labeling experiments showed that there was no direct relationship between the Thea synthesis and the preference of tea plants for NH 4 + .

Physiological and Molecular Analysis of Applied Nitrogen in Rice Genotypes

Ten genotypes of rice (Oryza sativa L.) were grown for 30 d in complete nutrient solution with 1 mmol/L (N-insufficient), 4 mmol/L (N-moderate) and 10 mmol/L (N-high) nitrogen levels, and nitrogen efficiency (NE) was analyzed. Growth performance, measured in terms of fresh weight, dry weight and lengths of root and shoot, was higher in N-efficient than in N-inefficient rice genotypes at low N level. Of these 10 genotypes, Suraksha was identified as the most N-efficient, while Vivek Dhan the most N-inefficient. To find out the physiological basis of this difference, the nitrate uptake rate of root and the activities of nitrate assimilatory enzymes in leaves of N-efficient and N-inefficient rice genotypes were studied. Uptake experiments revealed the presence of two separate nitrate transporter systems mediating high- and low-affinity nitrate uptake. Interestingly, the nitrate uptake by the roots of Suraksha is mediated by both high- and low-affinity nitrate transporter systems, while that of Vivek Dhan by only low-affinity nitrate transporter system. Study of the activities and expression levels of nitrate assimilatory enzymes in N-efficient and N-inefficient rice genotypes showed that nitrate reductase (NR) and glutamine synthetase (GS) play important roles in N assimilation under low-nitrogen conditions.

Fractionation of Stable Zinc Isotopes in the Field-Grown Zinc Hyperaccumulator Noccaea caerulescens and the Zinc-Tolerant Plant Silene vulgaris

Stable Zn isotope signatures offer a potential tool for tracing Zn uptake and transfer mechanisms within plant-soil systems. Zinc isotopic compositions were determined in the Zn hyperaccumulator Noccaea caerulescens collected at a Zn-contaminated site (Viviez), a serpentine site (Vosges), and a noncontaminated site (Sainte Eulalie) in France. Meanwhile, a Zn-tolerant plant ( Silene vulgaris ) was also collected at Viviez for comparison. While δ(66)Zn was substantially differentiated among N. caerulescens from the three localities, they all exhibited an enrichment in heavy Zn isotopes of 0.40-0.72‰ from soil to root, followed by a depletion in heavy Zn from root to shoot (-0.10 to -0.50‰). The enrichment of heavy Zn in roots is ascribed to the transport systems responsible for Zn absorption into root symplast and root-to-shoot translocation, while the depletion in heavy Zn in shoots is likely to be mediated by a diffusive process and an efficient translocation driven by energy-required transporters (e.g., NcHMA4). The mass balance yielded a bulk Zn isotopic composition between plant and soil (Δ(66)Zn(plant-soil)) of -0.01‰ to 0.63‰ in N. caerulescens , indicative of high- and/or low-affinity transport systems operating in the three ecotypes. In S. vulgaris , however, there was no significant isotope fractionation between whole plant and rhizosphere soil and between root and shoot, suggesting that this species appears to have a particular Zn homeostasis. We confirm that quantifying stable Zn isotopes is useful for understanding Zn accumulation mechanisms in plants.

Cadmium inhibits the induction of high-affinity nitrate uptake in maize (Zea mays L.) roots

Cadmium (Cd) detoxification involves glutathione and phytochelatins biosynthesis: the higher need of nitrogen should require increased nitrate (NO(3)(-)) uptake and metabolism. We investigated inducible high-affinity NO(3)(-) uptake across the plasma membrane (PM) in maize seedlings roots upon short exposure (10 min to 24 h) to low Cd concentrations (0, 1 or 10 μM): the activity and gene transcript abundance of high-affinity NO(3)(-) transporters, NO(3)(-) reductases and PM H(+)-ATPases were analyzed. Exposure to 1 mM NO(3)(-) led to a peak in high-affinity (0.2 mM) NO(3)(-) uptake rate (induction), which was markedly lowered in Cd-treated roots. Plasma membrane H(+)-ATPase activity was also strongly limited, while internal NO(3)(-) accumulation and NO(3)(-) reductase activity in extracts of Cd treated roots were only slightly lowered. Kinetics of high- and low-affinity NO(3)(-) uptake showed that Cd rapidly (10 min) blocked the inducible high-affinity transport system; the constitutive high-affinity transport system appeared not vulnerable to Cd and the low-affinity transport system appeared to be less affected and only after a prolonged exposure (12 h). Cd-treatment also modified transcript levels of genes encoding high-affinity NO(3)(-) transporters (ZmNTR2.1, ZmNRT2.2), PM H(+)-ATPases (ZmMHA3, ZmMHA4) and NO(3)(-) reductases (ZmNR1, ZmNADH:NR). Despite an expectable increase in NO(3)(-) demand, a negative effect of Cd on NO(3)(-) nutrition is reported. Cd effect results in alterations at the physiological and transcriptional levels of NO(3)(-) uptake from the external solution and it is particularly severe on the inducible high-affinity anion transport system. Furthermore, Cd would limit the capacity of the plant to respond to changes in NO(3) (-) availability.

Differential response of wheat genotypes to applied nitrogen: biochemical and molecular analysis

Nitrogen-efficient and nitrogen-inefficient wheat genotypes were identified on the basis of the differential response of 16 wheat genotypes with low (1 mM) and high (25 mM) nitrogen (N) supply. Growth performance, measured in terms of fresh weight, dry weight and length of root and shoot, was higher in N-efficient than N-inefficient wheat genotypes at low N levels. Interestingly, although the growth of N-efficient genotypes did not show any change with increasing level of N supply, there was a marked increase in the growth of N-inefficient genotypes with the increase in N level. To work out the basis of this differential response of wheat genotypes to low N levels, we investigated the nitrate uptake rate of root and activities of nitrate assimilatory enzymes in the leaves of N-efficient and N-inefficient wheat genotypes. Nitrate uptake kinetics of these genotypes revealed that the uptake of nitrate in N-efficient genotypes was mediated by high-affinity nitrate transporter systems, whereas those of N-inefficient genotypes was mediated by low-affinity nitrate transporter systems. Study of the activities and expression levels of nitrate assimilatory enzymes in N-efficient and N-inefficient wheat genotypes showed that nitrate reductase (NR) and glutamine synthetase (GS) play important roles in N assimilation under low-nitrogen conditions.

Kinetics of NH 4 + uptake by the arbuscular mycorrhizal fungus Rhizophagus irregularis

The kinetics and energetics of (15)NH (4) (+) uptake by the extraradical mycelium of the arbuscular mycorrhizal fungus Rhizophagus irregularis were investigated. (15)NH (4) (+) uptake increased with increasing substrate concentration over the concentration range of 0.002 to 25mM. Eadie-Hofstee plots showed that ammonium (NH (4) (+) ) uptake over this range was biphasic. At concentrations below 100μM, NH (4) (+) uptake fits a Michaelis-Menten curve, typical of the activity of a saturable high-affinity transport system (HATS). At concentrations above 1mM, NH (4) (+) influx showed a linear response typical of a nonsaturable low-affinity transport system (LATS). Both transport systems were dependent on external pH. The HATS and, to a lesser extent, the LATS were inhibited by the ionophore carbonylcyanide m-chlorophenylhydrazone (CCCP) and the ATP-synthesis inhibitor 2,4-dinitrophenol. These data indicate that the two NH (4) (+) transport systems of R. irregularis are dependent on metabolic energy and on the electrochemical H(+) gradient. The HATS- and the LATS-mediated (15)NH (4) (+) influxes were also regulated by acetate. This first report of the existence of active high- and low-affinity NH4(+) transport systems in the extraradical mycelium of an arbuscular mycorrhizal fungus and provides novel information on the mechanisms underlying mycosymbiont uptake of nitrogen from the soil environment.

Transport of selenium across the plasma membrane of primary hepatocytes and enterocytes of rainbow trout

Transport of essential solutes across biological membranes is one of the fundamental characteristics of living cells. Although selenium is an essential micronutrient, little is known about the cellular mechanisms of chemical species-specific selenium transport in fish. We report here the kinetic and pharmacological transport characteristics of selenite and its thiol (glutathione and l-cysteine) derivatives in primary cultures of hepatocytes and isolated enterocytes of rainbow trout. Findings from the current study suggest an apparent low-affinity linear transport system for selenite in both cell types. However, we recorded high-affinity Hill kinetics (K(d)=3.61±0.28 μmol l(-1)) in enterocytes exposed to selenite in the presence of glutathione. The uptake of selenite in the presence of thiols was severalfold higher than uptake of selenite alone (at equimolar concentration) in both hepatocytes and enterocytes. Cellular accumulation of selenium was found to be energy independent. Interestingly, we observed a decrease in selenite transport with increasing pH, whereas selenite uptake increased with increasing pH in the presence glutathione in both cell types. The cellular uptake of selenite demonstrated a pronounced competitive interaction with a structurally similar compound, sulfite. The uptake of selenite as well as its thiol derivatives was found to be sensitive to the anion transport blocker DIDS, irrespective of the cell type. Inorganic mercury (Hg(2+)) elicited an inhibition of selenite transport in both cell types, but augmented the transport of reduced forms of selenite in hepatocytes. Based on the substrate choice and comparable pharmacological properties, we advocate that multiple anion transport systems are probably involved in the cellular transport of selenite in fish.

An emerging protagonist: Sodium Glucose Co-transporters (SGLTs) as a burgeoning target for the treatment of diabetes mellitus

AbstractContemporary therapies to rationalize the hyperglycaemia in type 2 diabetes mellitus (T2DM) generally involve insulin-dependent mechanisms and lose their effectiveness as pancreatic b-cell function decreases to a greater extent. The kidney emerges out as a novel and potential target to trim down the T2DM. The filtered glucose is reabsorbed principally through the sodium glucose co-transporter-2 (SGLT2), a low affinity transport system, which is present at the luminal surface cells that cover the first segment of proximal tubules. Competitive inhibition of SGLT2 therefore represents an innovative therapeutic strategy for the treatment of hyperglycaemia and/or obesity in patients with type 1 or type 2 diabetes by enhancing glucose and energy loss through the urine. Selective inhibitors of SGLT2 reduce glucose reabsorption, causing excess glucose to be eliminated in the urine; this decreases plasma glucose. SGLT2 inhibitors are coupled with osmotic dieresis and loss of weight which aid in reducing blood pressure. The observation that individuals with familial renal glycosuria maintain normal long-term kidney function provides some encouragement that this mode of action will not adversely affect renal function. This novel mechanism of targeting the kidney for the treatment of T2DM is reasonably valuable and is independent of insulin and clutch with the low risk of hypoglycemia.

An emerging protagonist: Sodium Glucose Co-transporters (SGLTs) as a burgeoning target for the treatment of diabetes mellitus

Contemporary therapies to rationalize the hyperglycaemia in type 2 diabetes mellitus (T2DM) generally involve insulin-dependent mechanisms and lose their effectiveness as pancreatic b-cell function decreases to a greater extent. The kidney emerges out as a novel and potential target to trim down the T2DM. The filtered glucose is reabsorbed principally through the sodium glucose co-transporter-2 (SGLT2), a low affinity transport system, which is present at the luminal surface cells that cover the first segment of proximal tubules. Competitive inhibition of SGLT2 therefore represents an innovative therapeutic strategy for the treatment of hyperglycaemia and/or obesity in patients with type 1 or type 2 diabetes by enhancing glucose and energy loss through the urine. Selective inhibitors of SGLT2 reduce glucose reabsorption, causing excess glucose to be eliminated in the urine; this decreases plasma glucose. SGLT2 inhibitors are coupled with osmotic dieresis and loss of weight which aid in reducing blood pressure. The observation that individuals with familial renal glycosuria maintain normal long-term kidney function provides some encouragement that this mode of action will not adversely affect renal function. This novel mechanism of targeting the kidney for the treatment of T2DM is reasonably valuable and is independent of insulin and clutch with the low risk of hypoglycemia.

Mathematical modeling of the low and high affinity arabinose transport systems in Escherichia coli

A mathematical model was developed for the low and high affinity arabinose transport systems in E. coli. The model is a system of three ordinary differential equations and takes the dynamics of mRNAs for the araE and araFGH proteins and the internal arabinose into account. Special attention was paid to estimate the model parameters from the literature. Our analysis and simulations suggest that the high affinity transport system helps the low affinity transport system to respond to high concentration of extracellular arabinose faster, whereas the high affinity transport system responds to a small amount of extracellular arabinose. Steady state analysis of the model also predicts that there is a regime for the extracellular concentration of arabinose where the arabinose system can show bistable behavior.