Acute hypercapnic hyperoxia stimulates reactive species production in the caudal solitary complex of rat brain slices but does not induce oxidative stress
Central CO2 chemoreceptive neurons in the caudal solitary complex (cSC) are stimulated by hyperoxia via a free radical mechanism. Hyperoxia has been shown to increase superoxide and nitric oxide in the cSC, but it remains unknown how changes in Pco2 during hyperoxia affect the production of O2-dependent reactive oxygen and nitrogen species (RONS) downstream that can lead to increased levels of oxidative and nitrosative stress, cellular excitability, and, potentially, dysfunction. We used real-time fluorescence microscopy in rat brain slices to determine how hyperoxia and hypercapnic acidosis (HA) modulate one another in th...
Source: AJP: Cell Physiology - December 11, 2016 Category: Cytology Authors: Ciarlone, G. E., Dean, J. B. Tags: ARTICLES Source Type: research
Normobaric hyperoxia stimulates superoxide and nitric oxide production in the caudal solitary complex of rat brain slices
Central CO2-chemosensitive neurons in the caudal solitary complex (cSC) are stimulated not only by hypercapnic acidosis, but by hyperoxia as well. While a cellular mechanism for the CO2 response has yet to be isolated, previous data show that a redox-sensitive mechanism underlies neuronal excitability to hyperoxia. However, it remains unknown how changes in Po2 affect the production of reactive oxygen and nitrogen species (RONS) in the cSC that can lead to increased cellular excitability and, with larger doses, to cellular dysfunction and death. To this end, we used fluorescence microscopy in real time to determine how nor...
Source: AJP: Cell Physiology - December 11, 2016 Category: Cytology Authors: Ciarlone, G. E., Dean, J. B. Tags: ARTICLES Source Type: research
Expression of the mitochondrial calcium uniporter in cardiac myocytes improves impaired mitochondrial calcium handling and metabolism in simulated hyperglycemia
Diabetic cardiomyopathy is associated with metabolic changes, including decreased glucose oxidation (Gox) and increased fatty acid oxidation (FAox), which result in cardiac energetic deficiency. Diabetic hyperglycemia is a pathophysiological mechanism that triggers multiple maladaptive phenomena. The mitochondrial Ca2+ uniporter (MCU) is the channel responsible for Ca2+ uptake in mitochondria, and free mitochondrial Ca2+ concentration ([Ca2+]m) regulates mitochondrial metabolism. Experiments with cardiac myocytes (CM) exposed to simulated hyperglycemia revealed reduced [Ca2+]m and MCU protein levels. Therefore, we investig...
Source: AJP: Cell Physiology - December 11, 2016 Category: Cytology Authors: Diaz-Juarez, J., Suarez, J., Cividini, F., Scott, B. T., Diemer, T., Dai, A., Dillmann, W. H. Tags: ARTICLES Source Type: research
Myosin light chain kinase mediates intestinal barrier dysfunction via occludin endocytosis during anoxia/reoxygenation injury
Intestinal anoxia/reoxygenation (A/R) injury induces loss of barrier function followed by epithelial repair. Myosin light chain kinase (MLCK) has been shown to alter barrier function via regulation of interepithelial tight junctions, but has not been studied in intestinal A/R injury. We hypothesized that A/R injury would disrupt tight junction barrier function via MLCK activation and myosin light chain (MLC) phosphorylation. Caco-2BBe1 monolayers were subjected to anoxia for 2 h followed by reoxygenation in 21% O2, after which barrier function was determined by measuring transepithelial electrical resistance (TER) and FITC...
Source: AJP: Cell Physiology - December 11, 2016 Category: Cytology Authors: Jin, Y., Blikslager, A. T. Tags: ARTICLES Source Type: research
Adenosine triphosphate is a critical determinant for VEGFR signal during hypoxia
In this study, we examined alterations in VEGF signaling during hypoxia conditions and its determinant in endothelial cells. To analyze VEGF signaling during hypoxia, human umbilical vein endothelial cells (HUVECs) were exposed to 3 h of hypoxia (1% O2) followed by 3 h of reoxygenation or 12 h of hypoxia. Hypoxia induced expression of VEGF mRNA, but it was not associated with an increase in tube formation by HUVECs. During 3 h of hypoxia, VEGF-induced phosphorylation of VEGF receptor-2 (VEGFR-2) and downstream molecules were significantly inhibited without a change in VEGFR-2 expression, but it was completely restored afte...
Source: AJP: Cell Physiology - December 11, 2016 Category: Cytology Authors: Al Mamun, A., Hayashi, H., Sakima, M., Sato, M. Tags: ARTICLES Source Type: research
Lysophosphatidic acid-induced vascular neointimal formation in mouse carotid arteries is mediated by the matricellular protein CCN1/Cyr61
Vascular smooth muscle cell (SMC) migration is an essential step involved in neointimal formation in restenosis and atherosclerosis. Lysophosphatidic acid (LPA) is a bioactive component of oxidized low-density lipoprotein and is produced by activated platelets, implying that LPA influences vascular remodeling. Our previous study revealed that matricellular protein CCN1, a prominent extracellular matrix (ECM) protein, mediates LPA-induced SMC migration in vitro. Here we examined the role of CCN1 in LPA-induced neointimal formation. By using LPA infusion of carotid artery in a mouse model, we demonstrated that LPA highly ind...
Source: AJP: Cell Physiology - December 11, 2016 Category: Cytology Authors: Hao, F., Zhang, F., Wu, D. D., An, D., Shi, J., Li, G., Xu, X., Cui, M.-Z. Tags: ARTICLES Source Type: research
Oxyradical stress increases the biosynthesis of 2-arachidonoylglycerol: involvement of NADPH oxidase
NADPH oxidase (Nox)-derived oxyradicals contribute to atherosclerosis by oxidizing low-density lipoproteins (LDL), leading to their phagocytosis by vascular macrophages. Endocannabinoids, such as 2-arachidonoylglycerol (2-AG), might be an important link between oxidative stress and atherosclerosis. We hypothesized that 2-AG biosynthesis in macrophages is enhanced following ligation of oxidized LDL by scavenger receptors via a signal transduction pathway involving Nox-derived ROS that activates diacylglycerol lipase-β (DAGL-β), the 2-AG biosynthetic enzyme. To test this idea, we challenged macrophage cell lines an...
Source: AJP: Cell Physiology - December 11, 2016 Category: Cytology Authors: Matthews, A. T., Lee, J. H., Borazjani, A., Mangum, L. C., Hou, X., Ross, M. K. Tags: CALL FOR PAPERS Source Type: research
Mouse Slc4a11 expressed in Xenopus oocytes is an ideally selective H+/OH- conductance pathway that is stimulated by rises in intracellular and extracellular pH
The SLC4A11 gene encodes the bicarbonate-transporter-related protein BTR1, which is mutated in syndromes characterized by vision and hearing loss. Signs of these diseases [congenital hereditary endothelial dystrophy (CHED) and Harboyan syndrome] are evident in mouse models of Slc4a11 disruption. However, the intrinsic activity of Slc4a11 remains controversial, complicating assignment of its (patho)physiological role. Most studies concur that Slc4a11 transports H+ (or the thermodynamically equivalent species OH–) rather than HCO3–, but disparities have arisen as to whether the transport is coupled to another spe...
Source: AJP: Cell Physiology - December 11, 2016 Category: Cytology Authors: Myers, E. J., Marshall, A., Jennings, M. L., Parker, M. D. Tags: ARTICLES Source Type: research
H(OH), H(OH), H(OH): a holiday perspective. Focus on "Mouse Slc4a11 expressed in Xenopus oocytes is an ideally selective H+/OH- conductance pathway that is stimulated by rises in intracellular and extracellular pH"
(Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - December 11, 2016 Category: Cytology Authors: Nehrke, K. Tags: EDITORIAL FOCUS Source Type: research
A role for sodium-chloride cotransporters in the rapid regulation of ion uptake following acute environmental acidosis: new insights from the zebrafish model
The effects of acute exposure to acidic water on Na+ and Cl– homeostasis, and the mechanisms underlying their compensatory regulation, were investigated in the larval zebrafish Danio rerio. Exposure to acidic water (pH 4.0; control pH 7.6) for 2 h significantly reduced Na+ uptake and whole body Na+ content. Nevertheless, the capacity for Na+ uptake was substantially increased in fish preexposed to acidic water but measured in control water. Based on the accumulation of the Na+-selective dye, Sodium Green, two ionocyte subtypes exhibited intracellular Na+ enrichment after preexposure to acidic water: H+-ATPase rich (H...
Source: AJP: Cell Physiology - November 30, 2016 Category: Cytology Authors: Kwong, R. W. M., Perry, S. F. Tags: ARTICLES Source Type: research
Ca2+ permeability and Na+ conductance in cellular toxicity caused by hyperactive DEG/ENaC channels
Hyperactivated DEG/ENaC channels cause neuronal death mediated by intracellular Ca2+ overload. Mammalian ASIC1a channels and MEC-4(d) neurotoxic channels in Caenorhabditis elegans both conduct Na+ and Ca2+, raising the possibility that direct Ca2+ influx through these channels contributes to intracellular Ca2+ overload. However, we showed that the homologous C. elegans DEG/ENaC channel UNC-8(d) is not Ca2+ permeable, yet it is neurotoxic, suggesting that Na+ influx is sufficient to induce cell death. Interestingly, UNC-8(d) shows small currents due to extracellular Ca2+ block in the Xenopus oocyte expression system. Thus, ...
Source: AJP: Cell Physiology - November 30, 2016 Category: Cytology Authors: Matthewman, C., Miller-Fleming, T. W., Miller, D. M., Bianchi, L. Tags: ARTICLES Source Type: research
Hematopoietic stem and progenitor cells as novel prognostic biomarkers of longevity in a murine model for amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a difficult diagnosis and prognosis. In this regard, new and more reliable biomarkers for the disease are needed. We propose peripheral blood, and, more specifically, the hematopoietic stem and progenitor cells (HSPCs) as potential prognostic biomarkers in the SOD1G93A murine model of ALS. We accurately and serially studied three HSPCs—hematopoietic stem cells (HSCs), common lymphoid progenitors (CLPs), and common myeloid progenitors (CMPs)—in both control and SOD1G93A mice along the disease's progression by RT-PCR and flow cytometry ...
Source: AJP: Cell Physiology - November 30, 2016 Category: Cytology Authors: Gasco, S., Rando, A., Zaragoza, P., Garcia-Redondo, A., Calvo, A. C., Osta, R. Tags: ARTICLES Source Type: research
Defects in brainstem neurons associated with breathing and motor function in the Mecp2R168X/Y mouse model of Rett syndrome
Rett Syndrome (RTT) is an X-linked neurodevelopmental disorder caused mostly by disruption of the MECP2 gene. Among several RTT-like mouse models, one of them is a strain of mice that carries an R168X point mutation in Mecp2 and resembles one of the most common RTT-causing mutations in humans. Although several behavioral defects have previously been found in the Mecp2R168X/Y mice, alterations in nerve cells remain unknown. Here we compare several behavioral and cellular outcomes between this Mecp2R168X/Y model and a widely used Mecp2Bird/Y mouse model. With lower body weight and shorter lifespan than their wild-type litter...
Source: AJP: Cell Physiology - November 30, 2016 Category: Cytology Authors: Johnson, C. M., Zhong, W., Cui, N., Wu, Y., Xing, H., Zhang, S., Jiang, C. Tags: ARTICLES Source Type: research
Functional and molecular identification of a TASK-1 potassium channel regulating chloride secretion through CFTR channels in the shark rectal gland: implications for cystic fibrosis
In the shark rectal gland (SRG), apical chloride secretion through CFTR channels is electrically coupled to a basolateral K+ conductance whose type and molecular identity are unknown. We performed studies in the perfused SRG with 17 K+ channel inhibitors to begin this search. Maximal chloride secretion was markedly inhibited by low-perfusate pH, bupivicaine, anandamide, zinc, quinidine, and quinine, consistent with the properties of an acid-sensitive, four-transmembrane, two-pore-domain K+ channel (4TM-K2P). Using PCR with degenerate primers to this family, we identified a TASK-1 fragment in shark rectal gland, brain, gill...
Source: AJP: Cell Physiology - November 30, 2016 Category: Cytology Authors: Telles, C. J., Decker, S. E., Motley, W. W., Peters, A. W., Mehr, A. P., Frizzell, R. A., Forrest, J. N. Tags: ARTICLES Source Type: research
Transcriptional regulation of importin-{alpha}1 by JunD modulates subcellular localization of RNA-binding protein HuR in intestinal epithelial cells
The RNA-binding protein HuR is crucial for normal intestinal mucosal regeneration by modulating the stability and translation of target mRNAs, but the exact mechanism underlying HuR trafficking between the cytoplasm and nucleus remains largely unknown. Here we report a novel function of transcription factor JunD in the regulation of HuR subcellular localization through the control of importin-α1 expression in intestinal epithelial cells (IECs). Ectopically expressed JunD specifically inhibited importin-α1 at the transcription level, and this repression is mediated via interaction with CREB-binding site that was...
Source: AJP: Cell Physiology - November 30, 2016 Category: Cytology Authors: Xu, Y., Chen, J., Xiao, L., Chung, H. K., Zhang, Y., Robinson, J. C., Rao, J. N., Wang, J.-Y. Tags: CALL FOR PAPERS Source Type: research
