Association between Soluble α-Klotho Protein and Metabolic Syndrome in the Adult Population

Klotho protein is an anti-aging protein and plays multiple roles in ion-regulation, anti-oxidative stress, and energy metabolism through various pathways. Metabolic syndrome is a combination of multiple conditions that compose of multiple risk factors of cardiovascular disease and type 2 diabetes. Gene regulation and protein expression are discovered associated with metabolic syndrome. We aimed to figure out the correlation between Klotho protein and metabolic syndrome in generally healthy adults. A cross-sectional study of 9976 respondents ≥ 18 years old from the US National Health and Nutrition Examination Survey (2007–2012) by utilizing their soluble Klotho protein concentrations. Multivariate linear regression models were used to analyze the effect of soluble Klotho protein on the prevalence of metabolic syndrome. Soluble Klotho protein concentration was inversely correlated with the presence of metabolic syndromes (p = 0.013) and numbers of components that met the definition of metabolic syndrome (p < 0.05). The concentration of Soluble Klotho protein was negatively associated with abdominal obesity and high triglyceride (TG) in the adjusted model (p < 0.05). Soluble Klotho protein is correlated with changing metabolic syndrome components in adults, especially central obesity and high TG levels. Despite conventional function as co-factor with fibroblast growth factor-23 (FGF23) that regulates phosphate and vitamin D homeostasis, FGF23-independent soluble Klotho protein may act on multiple signal pathways in different organs and tissue in roles of anti-aging and protection from metabolic syndrome.

Cation-Chloride Cotransporters, Na/K Pump, and Channels in Cell Water and Ion Regulation: In silico and Experimental Studies of the U937 Cells Under Stopping the Pump and During Regulatory Volume Decrease

Cation-coupled chloride cotransporters play a key role in generating the Cl– electrochemical gradient on the cell membrane, which is important for regulation of many cellular processes. However, a quantitative analysis of the interplay between numerous membrane transporters and channels in maintaining cell ionic homeostasis is still undeveloped. Here, we demonstrate a recently developed approach on how to predict cell ionic homeostasis dynamics when stopping the sodium pump in human lymphoid cells U937. The results demonstrate the reliability of the approach and provide the first quantitative description of unidirectional monovalent ion fluxes through the plasma membrane of an animal cell, considering all the main types of cation-coupled chloride cotransporters operating in a system with the sodium pump and electroconductive K+, Na+, and Cl– channels. The same approach was used to study ionic and water balance changes associated with regulatory volume decrease (RVD), a well-known cellular response underlying the adaptation of animal cells to a hypoosmolar environment. A computational analysis of cell as an electrochemical system demonstrates that RVD may happen without any changes in the properties of membrane transporters and channels due to time-dependent changes in electrochemical ion gradients. The proposed approach is applicable when studying truly active regulatory processes mediated by the intracellular signaling network. The developed software can be useful for calculation of the balance of the unidirectional fluxes of monovalent ions across the cell membrane of various cells under various conditions.

Evaluation of the Role of Na+/ K+ ATPase Ion Transporters and Na+/K+/ 2Cl and Na+/H+ Exchanger Cotransporters in Nephrons of Periophthalmus Waltoni Using Immunohistochemistry and Histology

Kidneys play an important role in regulating the balance of water and ions in freshwater and seawater fish. However, complex kidney structures impair a comprehensive understanding of kidney function. In this study, in addition to renal histology, Na+/K+/ATPase ion transporter proteins and Na+/K+/2Cl− and NHE3 cotransporters were located in Priophthalmus waltoni kidney tissue to evaluate the ion regulation abilities of epithelial cells in various parts of nephrons. The renal tubules are composed of proximal tubules and distal tubules, followed by collecting tubes and finally collecting ducts. Light microscope immunohistochemistry was utilized to locate Na+/ K+-ATPase along renal tubules and collecting ducts. However, the distribution of the Na+/K+-ATPase immune response varies in different sections. Na+/K+/CL− cotransporter positioning was reported only in collecting tubes and collecting ducts, and proximal tubes and distal tubes did not respond to Na+/K+/Cl− cotransporter immunolocalization. Immunohistochemical response for NHE3 localization was detected only at the apex of epithelial cells of proximal tubules and collecting tubes. The distal tubes showed negative reaction and the collecting ducts showed a weak response to NHE3 safety immunolocalization.

Estrogen-related receptor γ2 controls NaCl uptake to maintain ionic homeostasis

Estrogen-related receptors (ERRs) are known to function in mammalian kidney as key regulators of ion transport-related genes; however, a comprehensive understanding of the physiological functions of ERRs in vertebrate body fluid ionic homeostasis is still elusive. Here, we used medaka (Oryzias melastigma), a euryhaline teleost, to investigate how ERRs are involved in ion regulation. After transferring medaka from hypertonic seawater to hypotonic freshwater (FW), the mRNA expression levels of errγ2 were highly upregulated, suggesting that ERRγ2 may play a crucial role in ion uptake. In situ hybridization and immunofluorescence staining showed that errγ2 was specifically expressed in ionocytes, the cells responsible for Na+/Cl- transport. In normal FW, ERRγ2 morpholino knockdown caused reductions in the mRNA expression of Na+/Cl- cotransporter (NCC), the number of NCC ionocytes, Na+/Cl- influxes of ionocytes, and whole-body Na+/Cl- contents. In FW with low Na+ and low Cl-, the expression levels of mRNA for Na+/H+ exchanger 3 (NHE3) and NCC were both decreased in ERRγ2 morphants. Treating embryos with DY131, an agonist of ERRγ, increased the whole-body Na+/Cl- contents and ncc mRNA expression in ERRγ2 morphants. As such, medaka ERRγ2 may control Na+/Cl- uptake by regulating ncc and/or nhe3 mRNA expression and ionocyte number, and these regulatory actions may be subtly adjusted depending on internal and external ion concentrations. These findings not only provide new insights into the underpinning mechanism of actions of ERRs, but also enhance our understanding of their roles in body fluid ionic homeostasis for adaptation to changing environments during vertebrate evolution.

The Drought-Mediated Soybean GmNAC085 Functions as a Positive Regulator of Plant Response to Salinity

Abiotic stress factors, such as drought and salinity, are known to negatively affect plant growth and development. To cope with these adverse conditions, plants have utilized certain defense mechanisms involved in various aspects, including morphological, biochemical and molecular alterations. Particularly, a great deal of evidence for the biological importance of the plant-specific NAM, ATAF1/2, CUC2 (NAC) transcription factors (TFs) in plant adaptation to abiotic stress conditions has been reported. A previous in planta study conducted by our research group demonstrated that soybean (Glycine max) GmNAC085 mediated drought resistance in transgenic Arabidopsis plants. In this study, further characterization of GmNAC085 function in association with salt stress was performed. The findings revealed that under this condition, transgenic soybean plants overexpressing GmNAC085 displayed better germination rates than wild-type plants. In addition, biochemical and transcriptional analyses showed that the transgenic plants acquired a better defense system against salinity-induced oxidative stress, with higher activities of antioxidant enzymes responsible for scavenging hydrogen peroxide or superoxide radicals. Higher transcript levels of several key stress-responsive genes involved in the proline biosynthetic pathway, sodium ion transporter and accumulation of dehydrins were also observed, indicating better osmoprotection and more efficient ion regulation capacity in the transgenic lines. Taken together, these findings and our previous report indicate that GmNAC085 may play a role as a positive regulator in plant adaptation to drought and salinity conditions.

Deletion of the Wilms’ Tumor Suppressor Gene in the Cardiac Troponin-T Lineage Reveals Novel Functions of WT1 in Heart Development

Expression of Wilms’ tumor suppressor transcription factor (WT1) in the embryonic epicardium is essential for cardiac development, but its myocardial expression is little known. We have found that WT1 is expressed at low levels in 20–25% of the embryonic cardiomyocytes. Conditional ablation of WT1 using a cardiac troponin T driver (Tnnt2Cre) caused abnormal sinus venosus and atrium development, lack of pectinate muscles, thin ventricular myocardium and, in some cases, interventricular septum and cardiac wall defects, ventricular diverticula and aneurisms. Coronary development was normal and there was not embryonic lethality, although survival of adult mutant mice was reduced probably due to perinatal mortality. Adult mutant mice showed electrocardiographic anomalies, including increased RR and QRS intervals, and decreased PR intervals. RNASeq analysis identified differential expression of 137 genes in the E13.5 mutant heart as compared to controls. GO functional enrichment analysis suggested that both calcium ion regulation and modulation of potassium channels are deeply altered in the mutant myocardium. In summary, together with its essential function in the embryonic epicardium, myocardial WT1 expression is also required for normal cardiac development.