Ion homeostasis in differently adapted populations of Suaeda vera Forssk. ex J.F. Gmel. for phytoremediation of hypersaline soils.

Salt-accumulator species are of great interest for the phytoremediation of salt-affected soils to reclaim soil salinization, a major constraints causing germination retardation and growth restriction of plants as well as habitat degradation. Higher biomass production at ECe 23-36 dS m-1 indicated that this species grows better in high to moderate salinity that was linked to osmotic adjustment through higher ion accumulation (Na+, Cl‒, and Ca2+) and organic osmolytes (free amino acids and proline). Plants from highly and moderately saline habitats exhibited broader metaxylem vessels, which was associated with eased conduction of solutes leading to better growth. Leaf anatomical characteristics generally increased with increasing salinity except at the highest ECe 55 dS m-1. The increased leaf lamina thickness contributed to succulence because of increased storage parenchymatous spongy tissues (that can store high amounts of water), water contents and it is a reflection of maintaining ion homeostasis and colonizing hyper-saline soil. Reduced stomatal density and area under high salinity are critical to cope with environmental hazards. Under high salinity, compartmentalization of excessive Na+ and Cl- ions and accumulation of compatible osmolytes are directly related to high degree of salinity tolerance, and hence are useful for phyto-amelioration of salinity-impacted lands.

Salinity tolerance mechanism in Suaeda vera have been explored extensively, but these mechanisms have not been addressed in the context of soil-plant interaction and functioning connection between structural and functional features with respect to phytoremediation. This work aims to provide mechanistic insight into how different morphological and physio-anatomical mechanisms in differently adapted population of Suaeda vera operate in coordinated manner to maintain ionic homeostasis under high salinity that are useful for phytoremediation.

Functional traits for salinity tolerance in differently adapted populations of Fimbristylis complanata (Retz.).

Functional modifications in three populations of Fimbristylis complanata collected from differently salt effected habitats were evaluated. The populations were established in pots and treated with five NaCl levels (0, 100, 200, 300, and 400 mM). Population SH (collected from the highest salinities, ECe 37.94 dS m-1) exhibited better osmotic adjustment because of the higher accumulation of organic osmolytes under high salinities and was ranked as highly tolerant. Other features like an increased concentration of chlorophyll pigments ensured maintenance of photosynthetic capability, and accumulated higher K+ and Ca2+ contents that minimized the toxic effect of Na+ and maintained ion homeostasis. Salinity tolerance in the Lillah-Khewra foothills (LR) population (collected from moderately saline site, ECe 31.36 dS m-1) relied on the maintenance of shoot dry weight (SDW) and shoot and root length (RL) with a parallel accumulation of organic osmolytes and shoot Ca2+. This species is a stem succulent and can store excessive amount of salt in storage parenchyma, as indicated by the accumulation of high concentration of Na+ in shoot. The SH population, in particular, can be rated as the best for phytoremediation of salt-affected soils that accumulated more Na+ than other populations and concentration of osmolytes for turgor maintenance under high salinities. Novelty statement Fimbristylis is less explored, particularly no information available on salt tolerance of F. complanata exists in the literature.

Salt tolerance mechanisms in three Irano-Turanian Brassicaceae halophytes relatives of Arabidopsis thaliana.

Salt tolerance mechanisms were studied in three Irano-Turanian halophytic species from the Brassicaceae (Lepidium latifolium, L. perfoliatum and Schrenkiella parvula) and compared with the glycophyte Arabidopsis thaliana. According to seed germination under salt stress, L. perfoliatum was the most tolerant species, while L. latifolium and S. parvula were rather susceptible. Contrastingly, based on biomass production L. perfoliatum was more salt sensitive than the other two species. In S. parvula biomass was increased up to 2.8-fold by 100 mM NaCl; no significant growth reduction was observed even when exposed to 400 mM NaCl. Stable activities of antioxidative defense enzymes, nil or negligible accumulation of superoxide anion and hydrogen peroxide, as well as stable membrane integrity in the three halophytes revealed that no oxidative stress occurred in these tolerant species under salt stress. Proline levels increased in response to salt treatment. However, it contributed only by 0.3‒2.0% to the total osmolyte concentration in the three halophytes (at 400 mM NaCl) and even less (0.04%) in the glycophyte, A. thaliana (at 100 mM NaCl). Soluble sugars in all three halophytes and free amino acids pool in S. parvula decreased under salt treatment in contrast to the glycophyte, A. thaliana. The contribution of organic osmolytes to the total osmolyte pool increased by salt treatment in the roots, while decreased in halophyte and glycophyte, A. thaliana leaves. Interestingly, this reduction was compensated by a higher relative contribution of K in the leaves of the halophytes, but of Na in A. thaliana. Taken together, biomass data and biochemical indicators show that S. parvula is more salt tolerant than the two Lepidium species. Our data indicate that L. latifolium, as a perennial halophyte with a large biomass, is highly suitable for both restoration of saline habitats and saline agriculture.

Thermal history and gape of individual Mytilus californianus correlate with oxidative damage and thermoprotective osmolytes.

The ability of animals to cope with environmental stress depends - in part - on past experience, yet knowledge of the factors influencing an individual's physiology in nature remains underdeveloped. We used an individual monitoring system to record body temperature and valve gaping behavior of rocky intertidal zone mussels (Mytilus californianus). Thirty individuals were selected from two mussel beds (wave-exposed and wave-protected) that differ in thermal regime. Instrumented mussels were deployed at two intertidal heights (near the lower and upper edges of the mussel zone) and in a continuously submerged tidepool. Following a 23-day monitoring period, measures of oxidative damage to DNA and lipids, antioxidant capacities (catalase activity and peroxyl radical scavenging) and tissue contents of organic osmolytes were obtained from gill tissue of each individual. Univariate and multivariate analyses indicated that inter-individual variation in cumulative thermal stress is a predominant driver of physiological variation. Thermal history over the outplant period was positively correlated with oxidative DNA damage. Thermal history was also positively correlated with tissue contents of taurine, a thermoprotectant osmolyte, and with activity of the antioxidant enzyme catalase. Origin site differences, possibly indicative of developmental plasticity, were only significant for catalase activity. Gaping behavior was positively correlated with tissue contents of two osmolytes. Overall, these results are some of the first to clearly demonstrate relationships between inter-individual variation in recent experience in the field and inter-individual physiological variation, in this case within mussel beds. Such micro-scale, environmentally mediated physiological differences should be considered in attempts to forecast biological responses to a changing environment.

Serum-free non-toxic freezing solution for cryopreservation of human adipose tissue-derived mesenchymal stem cells.

OBJECTIVE: To develop a cost-effective, non-toxic and xeno-free freezing solution for the preservation of adipose tissue-derived stem cells (hADSC) with a long shelf-life. RESULTS: The potential of various hydrocolloids and organic osmolytes as cryoprotectants and individual components of phosphate buffered saline (PBS) as carrier media were evaluated to formulate a freezing solution for the cryopreservation of hADSCs. Among the hydrocolloids, the highest viability, 55 %, was achieved with post-thawed (after 48 h storage at -80 °C) hADSCs cryopreserved in 10 % (v/v) polyvinylpyrrolidone (PVP) using PBS as carrier media. 0.9 % NaCl was a superior carrier medium resulting an enhanced cell viability (70 %) when used in 10 % PVP than other components of PBS. A higher cell viability (81 %) was achieved when 10 % PVP/0.9 % NaCl was supplemented with 60 mM ectoin. The cryopreserved cells retained normal cytoskeletal distribution pattern and adipogenic and osteogenic differentiation ability during 14 and 21 days of incubation. CONCLUSION: A serum-free and non-toxic 10 % PVP/0.9 % NaCl/60 mM ectoin freezing solution was developed for cryopreservation of hADSC for application in tissue engineering and regenerative medicine.

Global discovery of high-NaCl-induced changes of protein phosphorylation.

High extracellular NaCl, such as in the renal medulla, can perturb and even kill cells, but cells mount protective responses that enable them to survive and function. Many high-NaCl-induced perturbations and protective responses are known, but the signaling pathways involved are less clear. Change in protein phosphorylation is a common mode of cell signaling, but there was no unbiased survey of protein phosphorylation in response to high NaCl. We used stable isotopic labeling of amino acids in cell culture coupled to mass spectrometry to identify changes in protein phosphorylation in human embryonic kidney (HEK 293) cells exposed to high NaCl. We reproducibly identify >8,000 unique phosphopeptides in 4 biological replicate samples with a 1% false discovery rate. High NaCl significantly changed phosphorylation of 253 proteins. Western analysis and targeted ion selection mass spectrometry confirm a representative sample of the phosphorylation events. We analyze the affected proteins by functional category to infer how altered protein phosphorylation might signal cellular responses to high NaCl, including alteration of cell cycle, cyto/nucleoskeletal organization, DNA double-strand breaks, transcription, proteostasis, metabolism of mRNA, and cell death.

Role of organic osmolytes in water homoeostasis in skin.

The ability to conserve water is fundamental to terrestrial life. A number of organs such as the kidney and the bladder have important roles in the regulation of body water balance. The epidermis of skin is also fundamental to this process, and it is in a constant battle to prevent loss of water to the external, dry environment. Given this important role of the epidermis as a barrier to water loss, it is perhaps surprising that many of the cellular mechanisms by which human keratinocytes achieve cell volume homoeostasis, maintain epidermal hydration and adapt to biological effects from environmental stressors such as ultraviolet radiation are poorly understood. This article reviews what is known thus far and speculates about other potential mechanisms through which skin conducts water homoeostasis, with a particular emphasis on the putative role of organic osmolytes.

Structural and Functional Strategies in Cenchrus Species to Combat Environmental Extremities Imposed by Multiple Abiotic Stresses.

Multiple abiotic stresses such as drought, salinity, heat, and cold stress prevailing in natural habitats affect plant growth and development. Different species modify their structural and functional traits to combat these abiotic stresses while growing in stressful environments. Cenchrus species, i.e., Cenchrus pennisetiformis, C. setiger, and C. prieurii are widely distributed grasses found growing all over the world. Samples from natural populations were collected from different ecological regions in the Punjab and Khyber Pakhtoonkhwa that were exposed to aridity, salinity, and cold, while one site was designated as normal control. In the present study, structural and functional modifications of three Cenchrus species under abiotic stresses were evaluated. It was expected that each Cenchrus species may evolve different strategies to cope with multiple abiotic stresses. All Cenchrus species responded differently whether growing in normal environment or stressful conditions. The most remarkable feature for survival in C. pennisetiformis under cold stress was increased inflorescence and increased stem and root lignification. C. prieurii showed better tolerance to saline and cold environments. C. setiger showed better development of leaf sheath anatomical traits. The structural and functional modifications in Cenchrus species such as development of mechanical tissues provided structural support, while dermal and parenchymatous tissues increased water storage capacity and minimized water loss. An increase in the concentration of organic osmolytes and ionic content aids turgor pressure maintenance and ionic content crucial for plant growth and development. It was concluded that structural and functional alterations in all Cenchrus species were very specific and critical for survival under different environmental stresses. The ecological fitness of these species relied on maintenance of growth and biomass production, and the development of mechanical, vascular, dermal and parenchyma tissues under stressful environmental conditions. Moreover, accumulation of beneficial ions (K+ and Ca2+) and organic osmolytes were critical in turgor maintenance, hence survival of Cenchrus spp.

Changes in translation rate modulate stress-induced damage of diverse proteins.

Proteostasis is the maintenance of the proper function of cellular proteins. Hypertonic stress disrupts proteostasis and causes rapid and widespread protein aggregation and misfolding in the nematode Caenorhabditis elegans. Optimal survival in hypertonic environments requires degradation of damaged proteins. Inhibition of protein synthesis occurs in response to diverse environmental stressors and may function in part to minimize stress-induced protein damage. We recently tested this idea directly and demonstrated that translation inhibition by acute exposure to cycloheximide suppresses hypertonicity-induced aggregation of polyglutamine::YFP (Q35::YFP) in body wall muscle cells. In this article, we further characterized the relationship between protein synthesis and hypertonic stress-induced protein damage. We demonstrate that inhibition of translation reduces hypertonic stress-induced formation and growth of Q35::YFP, Q44::YFP, and α-synuclein aggregates; misfolding of paramyosin and ras GTPase; and aggregation of multiple endogenous proteins expressed in diverse cell types. Activation of general control nonderepressible-2 (GCN-2) kinase signaling during hypertonic stress inhibits protein synthesis via phosphorylation of eukaryotic initiation factor-2α (eIF-2α). Inhibition of GCN-2 activation prevents the reduction in translation rate and greatly exacerbates the formation and growth of Q35::YFP aggregates and the aggregation of endogenous proteins. The current studies together with our previous work provide the first direct demonstration that hypertonic stress-induced reduction in protein synthesis minimizes protein aggregation and misfolding. Reduction in translation rate also serves as a signal that activates osmoprotective gene expression. The cellular proteostasis network thus plays a critical role in minimizing hypertonic stress-induced protein damage, in degrading stress-damaged proteins, and in cellular osmosensing and signaling.

Osmotic regulation of hepatic betaine metabolism.

Betaine critically contributes to the control of hepatocellular hydration and provides protection of the liver from different kinds of stress. To investigate how the hepatocellular hydration state affects gene expression of enzymes involved in the metabolism of betaine and related organic osmolytes, we used quantitative RT-PCR gene expression studies in rat hepatoma cells as well as metabolic and gene expression profiling in primary hepatocytes of both wild-type and 5,10-methylenetetrahydrofolate reductase (MTHFR)-deficient mice. Anisotonic incubation caused coordinated adaptive changes in the expression of various genes involved in betaine metabolism, in particular of betaine homocysteine methyltransferase, dimethylglycine dehydrogenase, and sarcosine dehydrogenase. The expression of betaine-degrading enzymes was downregulated by cell shrinking and strongly induced by an increase in cell volume under hypotonic conditions. Metabolite concentrations in the culture system changed accordingly. Expression changes were mediated through tyrosine kinases, cyclic nucleotide-dependent protein kinases, and JNK-dependent signaling. Assessment of hepatic gene expression using a customized microarray chip showed that hepatic betaine depletion in MTHFR(-/-) mice was associated with alterations that were comparable to those induced by cell swelling in hepatocytes. In conclusion, the adaptation of hepatocytes to changes in cell volume involves the coordinated regulation of betaine synthesis and degradation and concomitant changes in intracellular osmolyte concentrations. The existence of such a well-orchestrated response underlines the importance of cell volume homeostasis for liver function and of methylamine osmolytes such as betaine as hepatic osmolytes.

Digestive cells from Mytilus galloprovincialis show a partial regulatory volume decrease following acute hypotonic stress through mechanisms involving inorganic ions.

The response of isolated digestive cells of the digestive gland of Mytilus galloprovincialis to hypotonic shock was studied using videometric methods. The isolated cells exposed to a rapid change (from 1100 to 800 mosmol kg(-1) ) of the bathing solution osmolality swelled but thereafter underwent a regulatory volume decrease (RVD), tending to recover the original size. When the hypotonic stress was applied in the presence of quinine and glibenclamide, known inhibitors of swelling activated ion channels, the cells did not exhibit an RVD response; in addition, they showed a larger increase in size in respect to control cells. These observations suggest that the digestive cells of the digestive gland have the machinery to cope with the hyposmotic shock allowing them to exhibit a small but significant RVD preventing an excessive increase in cell size. The pharmacological treatment of digestive cells during the RVD experiments suggests that cell volume is regulated by K(+) and Cl(-) efflux followed by an obliged water efflux from the cell. The involvement of organic osmolytes such as taurine and betaine seems to be excluded by NMR measurement on digestive cells.

Structural and functional traits underlying the capacity of Calotropis procera to face different stress conditions.

Calotropis procera (Aiton) W. T. Aiton, originally native to tropical and sub-tropical regions of northwestern Africa to southwest Asia through the Arabian Peninsula. The present study was engaged to uncover the underlying mechanism (structural and functional) of C. procera sampled from six different ecological regions. The population of normal irrigated agriculture field (IAF) had better growth, high K+ ion content, photosynthetic pigments (chl a chl b, Tchl and caro) and stomatal density. The population of dust and pollution stressed habitat (IWD) exhibited enlarged epidermal cells in stem and leaf, enhanced cortical proportion with largest cells in stem and phloem area in leaf. The population of drought and aridity stressed habitat (ARS) showed increased root cellular area, cortical region thickness and its cell area, and phloem region. The population from salt-affected habitat (SLF) possessed high root and shoot ionic contents (Na+ and Ca2+), total soluble sugars, total antioxidant activity, chlorophyll a/b, widened metaxylem vessels and phloem area in the stem, while intensive sclerification observed in both stem and leaf. The population native to waterlogged and salinity stressed habitat (APC) represented vigorous root growth, total free amino acids, well-developed metaxylem vessels and stomatal area in leaf. The population from drought and salinity-prone habitat (UBL) indicate increased storage of parenchymatous tissue (pith region and its cells area) and epidermal cell area in leaf. It is concluded that C. procera showed much outmost behavior in view of growth, structural and functional attributes in response to prevailing environmental condition.

Comparative Analysis of Antioxidant System and Salt-Stress Tolerance in Two Hibiscus Cultivars Exposed to NaCl Toxicity.

Hibiscus (Hibiscus syriacus L.) is known as a horticultural plant of great ornamental and medicinal value. However, the effect of NaCl stress on hibiscus seedlings is unclear. Little is known about H. syriacus 'Duede Brabaul' (DB) and H. syriacus 'Blueberry Smoothie' (BS). Here, the effects of solutions with different concentrations of NaCl on the organic osmolytes, ion accumulation, and antioxidant enzyme activity of hibiscus seedling leaves were determined. The results showed that the Na+/K+ ratio was imbalanced with increasing NaCl concentration, especially in BS (range 34% to 121%), which was more sensitive than DB (range 32% to 187%) under NaCl concentrations of 50 to 200 mM. To cope with the osmotic stress, the content of organic osmolytes increased significantly. Additionally, NaCl stress caused a large increase in O2·- and H2O2, and other reactive oxygen species (ROS), and antioxidant enzyme activity was significantly increased to remove excess ROS. The expression level of genes related to salt tolerance was significantly higher in DB than that in BS under different NaCl concentrations. Taken together, DB possessed a stronger tolerance to salt stress and the results suggest membrane stability, Na+/K+, H2O2, catalase and ascorbate peroxidase as salt tolerance biomarkers that can be used for gene transformation and breeding in future hibiscus research.

Can hyper/hypo-osmoregulating fiddler crabs from the Atlantic coast of South America mobilize intracellular free amino acids as osmotic effectors during salinity challenge?

Weakly osmoregulating crustaceans use intracellular free amino acids (FAA) to attenuate cell volume changes consequent to alterations in hemolymph osmolality. Whether semiterrestrial, strong hyper/hypo-osmoregulators exhibit this ability is unknown. We investigate FAA mobilization in muscle tissue of 10 fiddler crabs from the genera Minuca, Leptuca, and Uca distributed along the Atlantic coast of South America. Crabs were subjected to severe hypo- or hyper-osmotic challenge at their lower or upper critical salinity limits for 5 days; reference crabs were held in isosmotic media. Hemolymph osmolality was measured, chela muscle FAA were identified and quantified, and percent contribution to intracellular osmolality (%FAA) was calculated. At isosmoticity, total FAA were nominally twofold higher in Minuca species (≈116 mmol/kg wet mass) compared to Uca (≈60 mmol/kg wet mass). Glycine, alanine, arginine, and taurine constituted >80% of the total FAA pool. On hyperosmotic challenge, hemolymph osmolalities ranged from 843 to 1282 mOsm/kg H2 O. FAA increased, although %FAA remained unaltered. Hypo-osmoregulating crabs thus can mobilize FAA, likely owing to a lesser ability to secrete salt near their upper critical limits. On hypo-osmotic challenge, osmolalities were regulated more tightly, between 475 and 736 mOsm/kg H2 O. Total FAA and %FAA showed little change, probably due to the crabs' strong hyper-osmotic extracellular regulatory ability, FAA consequently playing a diminished role in isosmotic intracellular regulation (IIR). Total FAA responses to hyper/hypo-osmotic challenge are thus asymmetrical. The lack of phylogenetic signal in FAA mobilization suggests that closely related fiddler crabs do not share similar strategies of IIR.

Foliar architecture and physio-biochemical plasticity determines survival of Typha domingensis pers. Ecotypes in nickel and salt affected soil.

Six ecotypes of Typha domingensis Pers. Jahlar (E1), Sheikhupura (E2), Sahianwala (E3), Gatwala (E4), Treemu (E5) and Knotti (E6) from different ecological regions were collected to evaluate the leaf anatomical and biochemical attributes under different levels of salinity and nickel stress viz; L0 (control), L1 (100 mM + 50 mg kg-1), L2 (200 mM + 100 mg kg-1) and L3 (300 mM + 150 mg kg-1). Presence of salt and Ni in rooting medium consistently affected growth, anatomical and physio-biochemical attributes in all Typha ecotypes. Discrete anatomical modifications among ecotypes such as reduced leaf thickness, increased parenchyma area, metaxylem cell area, aerenchyma formation and improved metaxylem vessels were recorded with increasing dose of salt and Ni. The minimum anatomical damages were recorded in E1 and E6 ecotypes. In all ecotypes, progressive perturbations in ionic homeostasis (Na+, K+, Cl-, N) due to salt and metal toxicity were evident along with reduction in photosynthetic pigments. Maximum enhancement in Catalase (CAT), Superoxide dismutase (SOD), Peroxidase (POD) and modulated Malondialdehyde (MDA) activity was recorded in E1 and E6 as compared to other ecotypes. Accumulation of large amounts of metabolites such as total soluble sugars, total free amino acids content in Jahlar, Knotti, Treemu and Sahianawala ecotypes under different levels of salt and Ni prevented cellular damages in T. domingensis Pers. The correlation analysis exhibited a close relationship among different levels of salinity and Ni with various plant attributes. PCA-Biplot verified our correlational analysis among various attributes of Typha ecotypes. An obvious separation of Typha characters in response to different salinity and Ni levels was exhibited by PC1. We recommend that genetic potential of T. domingensis Pers. To grow under salt and Ni stresses must be investigated and used for phytoremediation and reclamation of contaminated soil.

Comparison of Isotonic Activation of Cell Volume Regulation in Rat Peritoneal Mesothelial Cells and in Kidney Outer Medullary Collecting Duct Principal Cells.

In disease states, mesothelial cells are exposed to variable osmotic conditions, with high osmotic stress exerted by peritoneal dialysis (PD) fluids. They contain unphysiologically high concentrations of glucose and result in major peritoneal membrane transformation and PD function loss. The effects of isotonic entry of urea and myo-inositol in hypertonic (380 mOsm/kg) medium on the cell volume of primary cultures of rat peritoneal mesothelial cells and rat kidney outer medullary collecting duct (OMCD) principal cells were studied. In hypertonic medium, rat peritoneal mesothelial cells activated a different mechanism of cell volume regulation in the presence of isotonic urea (100 mM) in comparison to rat kidney OMCD principal cells. In kidney OMCD cells inflow of urea into the shrunken cell results in restoration of cell volume. In the shrunken peritoneal mesothelial cells, isotonic urea inflow caused a small volume increase and activated regulatory volume decrease (RVD). Isotonic myo-inositol activated RVD in hypertonic medium in both cell types. Isotonic application of both osmolytes caused a sharp increase of intracellular calcium both in peritoneal mesothelial cells and in kidney OMCD principal cells. In conclusion, peritoneal mesothelial cells exhibit RVD mechanisms when challenged with myo-inositol and urea under hyperosmolar isotonic switch from mannitol through involvement of calcium-dependent control. Myo-inositol effects were identical with the ones in OMCD principal cells whereas urea effects in OMCD principal cells led to no RVD induction.

The PKA-p38MAPK-NFAT5-Organic Osmolytes Pathway in Duchenne Muscular Dystrophy: From Essential Player in Osmotic Homeostasis, Inflammation and Skeletal Muscle Regeneration to Therapeutic Target.

In Duchenne muscular dystrophy (DMD), the absence of dystrophin from the dystrophin-associated protein complex (DAPC) causes muscle membrane instability, which leads to myofiber necrosis, hampered regeneration, and chronic inflammation. The resulting disabled DAPC-associated cellular pathways have been described both at the molecular and the therapeutical level, with the Toll-like receptor nuclear factor kappa-light-chain-enhancer of activated B cells pathway (NF-ƘB), Janus kinase/signal transducer and activator of transcription proteins, and the transforming growth factor-ß pathways receiving the most attention. In this review, we specifically focus on the protein kinase A/ mitogen-activated protein kinase/nuclear factor of activated T-cells 5/organic osmolytes (PKA-p38MAPK-NFAT5-organic osmolytes) pathway. This pathway plays an important role in osmotic homeostasis essential to normal cell physiology via its regulation of the influx/efflux of organic osmolytes. Besides, NFAT5 plays an essential role in cell survival under hyperosmolar conditions, in skeletal muscle regeneration, and in tissue inflammation, closely interacting with the master regulator of inflammation NF-ƘB. We describe the involvement of the PKA-p38MAPK-NFAT5-organic osmolytes pathway in DMD pathophysiology and provide a clear overview of which therapeutic molecules could be of potential benefit to DMD patients. We conclude that modulation of the PKA-p38MAPK-NFAT5-organic osmolytes pathway could be developed as supportive treatment for DMD in conjunction with genetic therapy.

Adaptive physiological water conservation explains hypertension and muscle catabolism in experimental chronic renal failure.

AIM: We have reported earlier that a high salt intake triggered an aestivation-like natriuretic-ureotelic body water conservation response that lowered muscle mass and increased blood pressure. Here, we tested the hypothesis that a similar adaptive water conservation response occurs in experimental chronic renal failure. METHODS: In four subsequent experiments in Sprague Dawley rats, we used surgical 5/6 renal mass reduction (5/6 Nx) to induce chronic renal failure. We studied solute and water excretion in 24-hour metabolic cage experiments, chronic blood pressure by radiotelemetry, chronic metabolic adjustment in liver and skeletal muscle by metabolomics and selected enzyme activity measurements, body Na+ , K+ and water by dry ashing, and acute transepidermal water loss in conjunction with skin blood flow and intra-arterial blood pressure. RESULTS: 5/6 Nx rats were polyuric, because their kidneys could not sufficiently concentrate the urine. Physiological adaptation to this renal water loss included mobilization of nitrogen and energy from muscle for organic osmolyte production, elevated norepinephrine and copeptin levels with reduced skin blood flow, which by means of compensation reduced their transepidermal water loss. This complex physiologic-metabolic adjustment across multiple organs allowed the rats to stabilize their body water content despite persisting renal water loss, albeit at the expense of hypertension and catabolic mobilization of muscle protein. CONCLUSION: Physiological adaptation to body water loss, termed aestivation, is an evolutionary conserved survival strategy and an under-studied research area in medical physiology, which besides hypertension and muscle mass loss in chronic renal failure may explain many otherwise unexplainable phenomena in medicine.

Formulas for fixing serum sodium: curb your enthusiasm.

A variety of formulas have been proposed to predict changes in serum sodium concentration. All are based on an experiment done over 50 years ago by Edelman, who derived a formula relating the plasma sodium concentration to isotopically measured body sodium, potassium, and water. Some of these formulas fail because they do not include urinary losses of electrolytes and water. Even those that include these essential variables are not accurate enough for clinical use because it is impractical to adjust calculations to rapid changes in urinary composition, and because the formulas do not account for changes in serum sodium caused by internal exchanges between soluble and bound sodium stores or shifts of water into or out of cells resulting from changes in intracellular organic osmolytes. Nephrologists should curb their enthusiasm for predictive formulas and rely instead on frequent measurements of the serum sodium when correcting hyponatremia and hypernatremia.

Green algae in alpine biological soil crust communities: acclimation strategies against ultraviolet radiation and dehydration.

Green algae are major components of biological soil crusts in alpine habitats. Together with cyanobacteria, fungi and lichens, green algae form a pioneer community important for the organisms that will succeed them. In their high altitudinal habitat these algae are exposed to harsh and strongly fluctuating environmental conditions, mainly intense irradiation, including ultraviolet radiation, and lack of water leading to desiccation. Therefore, green algae surviving in these environments must have evolved with either avoidance or protective strategies, as well as repair mechanisms for damage. In this review we have highlighted these mechanisms, which include photoprotection, photochemical quenching, and high osmotic values to avoid water loss, and in some groups flexibility of secondary cell walls to maintain turgor pressure even in water-limited situations. These highly specialized green algae will serve as good model organisms to study desiccation tolerance or photoprotective mechanisms, due to their natural capacity to withstand unfavorable conditions. We point out the urgent need for modern phylogenetic approaches in characterizing these organisms, and molecular methods for analyzing the metabolic changes involved in their adaptive strategies.