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American Journal of Physiology. Cell Physiology

Muriel Nobles, David Montaigne, Sonia Sebastian, Lutz Birnbaumer, Andrew Tinker
G-protein gated inwardly rectifying K+ (GIRK) channels are the major inwardly rectifying K+ currents in cardiac atrial myocytes and an important determinant of atrial electrophysiology. Inhibitory G-protein alpha subunits can both mediate activation via acetylcholine but can also supress basal currents in the absence of agonist. We studied this phenomenon using whole cell patch clamping in murine atria from mice with global genetic deletion of Gαi2, combined deletion of Gαi1/Gαi3 and littermate controls...
January 17, 2018: American Journal of Physiology. Cell Physiology
Kristoffer B Sugg, James F Markworth, Nathaniel P Disser, Andrew M Rizzi, Jeffrey R Talarek, Dylan C Sarver, Susan V Brooks, Christopher L Mendias
Platelet-derived growth factor receptor (PDGFR) signaling plays an important role in the fundamental biological activities of many cells that compose musculoskeletal tissues. However, little is known about the role of PDGFR signaling during tendon growth and remodeling in adult animals. Using the hindlimb synergist ablation model of tendon growth, our objectives were to determine the role of PDGFR signaling in the adaptation of tendons subjected to a mechanical growth stimulus, as well as to investigate the biological mechanisms behind this response...
December 13, 2017: American Journal of Physiology. Cell Physiology
Claudio F Perez, Jose M Eltit, Jose R Lopez, Dóra Bodnár, Angela F Dulhunty, Shouvik Aditya, Marco G Casarotto
Malignant Hyperthermia (MH) susceptibility has been recently linked to a novel variant of β1a subunit of the dihydropyridine receptor (DHPR), a channel essential for Ca2+ regulation in skeletal muscle. Here we evaluate the effect of the mutant variant V156A on the structure/function of DHPR β1a subunit and assess its role on Ca2+ metabolism of cultured myotubes. Using differential scanning fluorimetry we show that mutation V156A causes a significant reduction in thermal stability of the Src homology 3 (SH3)/Guanylate Kinase (GK) core domain of β1a subunit...
December 6, 2017: American Journal of Physiology. Cell Physiology
Yasaman Amoozadeh, Shaista Anwer, Qinghong Dan, Shruthi Venugopal, Yixuan Shi, Emily Branchard, Elisabeth Liedtke, Menachem Ailenberg, Ori D Rotstein, Andras Kapus, Katalin Szaszi
Claudin-2 (Cldn-2) is a channel-forming tight junction (TJ) protein in the proximal tubules that mediates paracellular Na+ transport and has also emerged as a regulator of proliferation and migration. Expression of Cldn-2 is altered by numerous stimuli, but the underlying mechanisms remain incompletely understood. Here we show that Cldn-2 protein and mRNA expression were low in sub-confluent tubular cells and increased during junction maturation. Cldn-1 or occludin did not exhibit similar confluence-dependence...
November 29, 2017: American Journal of Physiology. Cell Physiology
Yewei Liu, Sarah J Russell, Martin F Schneider
Foxo transcription factors promote protein breakdown and atrophy of skeletal muscle fibers. Foxo transcriptional effectiveness is largely determined by phosphorylation-dependent nucleo-cytoplasmic shuttling. Imaging Foxo1-GFP over time in 124 nuclei in 68 multi-nucleated adult skeletal muscle fibers under control culture conditions reveals large variability in Foxo1-GFP nucleo-cytoplasmic concentration ratio (N/C) and in the apparent rate coefficient (kI') for Foxo1-GFP unidirectional nuclear influx (measured with efflux blocked by leptomycin B)...
November 29, 2017: American Journal of Physiology. Cell Physiology
James Boslett, Craig Hemann, Fivos L Christofi, Jay L Zweier
The NAD(P)+-hydrolyzing enzyme CD38 is activated in the heart during the process of ischemia and reperfusion, triggering NAD(P)(H) depletion. However, the presence and role of CD38 in the major cell types of the heart are unknown. Therefore, we characterize the presence and function of CD38 in cardiac myocytes, endothelial cells, and fibroblasts. To comprehensively evaluate CD38 in these cells, we measured gene transcription via mRNA, as well as protein expression and enzymatic activity. Endothelial cells strongly expressed CD38, while only low expression was present in cardiac myocytes with intermediate levels in fibroblasts...
November 29, 2017: American Journal of Physiology. Cell Physiology
Luciana I Gallo, Marianela G Dalghi, Dennis R Clayton, Wily G Ruiz, Puneet Khandelwal, Gerard Apodaca
Umbrella cells, which must maintain a tight barrier, modulate their apical surface area during bladder filling by exocytosis of an abundant, subapical pool of discoidal- and/or fusiform-shaped vesicles (DFVs). Despite the importance of this trafficking event for bladder function, the pathways the promote DFV exocytosis remain to be identified. We previously showed that DFV exocytosis depends in part on a RAB11A-RAB8A-MYO5B network, but RAB27B is also reported to be associated with DFVs, and knockout mice lacking RAB27B have fewer DFVs...
November 22, 2017: American Journal of Physiology. Cell Physiology
Srinivas Aluri, Rongbao Zhao, Andras Fiser, I David Goldman
The proton-coupled folate transporter (PCFT-SLC46A1) is required for folate transport across the apical membrane of the small intestine and across the choroid plexus. This study focuses on the structure/function of the 7th transmembrane domain (TMD), and its relationship to the 8th TMD as assessed by the substituted cysteine accessibility method (SCAM) and dicysteine cross-linking. Nine exofacial residues (I278C; H281C-L288C) of 23 residues in the 7th TMD were accessible to 2-((Biotinoyl)amino)ethyl methanethiosulfonate (MTSEA-biotin)...
November 22, 2017: American Journal of Physiology. Cell Physiology
Matthew Alleyn, Mason Breitzig, Richard Lockey, Narasaiah Kolliputi
Posttranslational modifications affect almost all proteins and are critical to a well-functioning and diverse proteome; however, many modifications remain relatively unknown and unstudied. This paper will give a perspective on the rapidly developing, novel posttranslational modification called succinylation. This modification may be implicated in numerous diseases, such as hepatic, cardiac, and pulmonary diseases. Although the influences of this modification still remain poorly understood, we are confident that further research into succinylation will provide an enhanced understanding of the complex machinery within the mitochondria, as well as the imposing consequences associated with its dysfunction...
November 22, 2017: American Journal of Physiology. Cell Physiology
Shin-Haw Lee, Sina Hadipour-Lakmehsari, Tetsuaki Miyake, Anthony O Gramolini
The mammalian nucleus has invaginations from the cytoplasm, termed nucleoplasmic reticulum (NR). With increased resolution of cellular imaging, progress has been made in understanding the formation and function of NR. In fact, nucleoplasmic Ca2+ homeostasis has been implicated in the regulation of gene expression, DNA repair, and cell death. However, the majority of studies focus on cross-sectional or single plane analyses of NR invaginations, providing an incomplete assessment of its distribution and content...
November 22, 2017: American Journal of Physiology. Cell Physiology
Gleisy Kelly Goncalves, Sergio Scalzo, Ana Paula Alves, Ubirajara Agero, Silvia Guatimosim, Adelina M Reis
Estradiol (E2) prevents cardiac hypertrophy and these protective actions are mediated by estrogen receptor (ER)α and ERβ. The G protein-coupled estrogen receptor (GPER) mediates many estrogenic effects and its activation in the heart has been observed in ischemia and reperfusion injury or hypertension models. However, the underlying mechanisms need to be fully elucidated. Herein we investigated whether the protective effect of E2 against cardiomyocytes hypertrophy induced by Endothelin-1 (ET-1) is mediated by GPER and the signaling pathways involved...
November 22, 2017: American Journal of Physiology. Cell Physiology
John D Tompkins, Todd A Clason, Thomas R Buttolph, Beatrice M Girard, Anne K Linden, Jean C Hardwick, Laura A Merriam, Victor May, Rodney L Parsons
Pituitary adenylate cyclase activating polypeptide (PACAP, Adcyap1) activation of PAC1 receptors (Adcyap1r1) significantly increases excitability of guinea pig cardiac neurons. This modulation of excitability is mediated in part by plasma membrane G protein-dependent activation of adenylyl cyclase and downstream signaling cascades. However, additional mechanisms responsible for the enhanced excitability are activated following internalization of the PAC1 receptor and endosomal signaling. Src family kinases play critical roles mediating endocytosis of many trophic factor and G-protein coupled receptors...
November 15, 2017: American Journal of Physiology. Cell Physiology
Li-Fen Zhou, Qing-Zi Chen, Chun-Tao Yang, Zhao-Di Fu, Shen-Ting Zhao, Yan Chen, Shu-Ni Li, Li Liao, Yu-Bo Zhou, Jian-Rong Huang, Jian-Hua Li
Transient receptor potential canonical (TRPC) channels are currently an emerging target for airway disorders. Recent evidences have indicated that TRPC6 as a member of the TRPC family plays an important role in airway inflammation, but its precise function in bronchial epithelial cells remains unclear. The aim of this study was to investigate the role of TRPC6 in TLR4-mediated inflammation in human bronchial epithelial cells stimulated by endotoxin (lipopolysaccharide, LPS). Hyp9 is a simplified phloroglucinol derivative of Hyperforin which highly selective activates TRPC6 channels...
November 15, 2017: American Journal of Physiology. Cell Physiology
Bo Pan, Derek Toms, Julang Li
MicroRNAs (miRNAs) have been established as important regulators of gene expression in the mammalian ovary. A previous screen of small RNA in the porcine ovary identified the down regulation of miR-574 during oocyte maturation, although its role during this process was not established. Here, we found that miR-574 directly targets the transcript for hyaluron synthase 2 protein (HAS2), a key enzyme in the production of extracellular matrix by the surrounding cumulus cells. Inhibiting this miRNA during in vitro maturation (IVM) increased HAS2 levels along with several markers of oocyte quality...
November 15, 2017: American Journal of Physiology. Cell Physiology
Mazène Hochane, Denis Raison, Catherine Coquard, Claire Béraud, Audrey Bethry, Sabrina Danilin, Thierry Massfelder, Mariette Barthelmebs
Mesangial cell (MC) injury is a prominent feature of glomerulonephritis. Activated MC secretes inflammatory mediators which induce cell apoptosis. Parathyroid hormone-related peptide (PTHrP) is a locally active cytokine that enhances cell survival and is upregulated by pro-inflammatory factors in many cell types. The aim of this study was to analyze the regulation of PTHrP expression by inflammatory cytokines, and to evaluate whether PTHrP itself acts as a pro-inflammatory and/or survival factor on male murine MC in primary culture...
November 15, 2017: American Journal of Physiology. Cell Physiology
Rosica S Petrova, Kevin F Webb, Ehsan Vaghefi, Kerry Walker, Kevin L Schey, Paul J Donaldson
Although the functionality of the lens water channels, AQP1 (epithelium) and AQP0 (fiber cells), are well established less is known about the role of AQP5 in the lens. Since in other tissues AQP5 functions as a regulated water channel with a water permeability (PH2O) some 20x higher than AQP0, AQP5 could function to modulate PH2O in lens fiber cells. To test this possibility a fluorescence dye dilution assay was used to calculate the relative PH2O of epithelial cells and fiber membrane vesicles isolated from either the mouse or rat lens, in the absence and presence of HgCl2 - an inhibitor of AQP1 and AQP5...
November 8, 2017: American Journal of Physiology. Cell Physiology
Hui Yu, Xiaoyu Cui, Jue Zhang, Joe X Xie, Moumita Banerjee, Sandrine V Pierre, Zijian Xie
Of the four Na/K-ATPase α isoforms, the ubiquitous α1 Na/K-ATPase possesses both ion transport and Src-dependent signaling functions. Mechanistically, we have identified two putative pairs of domain interactions between α1 Na/K-ATPase and Src that are critical for α1 signaling. Our subsequent report that α2 Na/K-ATPase lacks these putative Src-binding sites and fails to carry on Src-dependent signaling further supported our proposed model of direct interaction between α1 Na/K-ATPase and Src, but fell short of providing evidence for a causative role...
November 8, 2017: American Journal of Physiology. Cell Physiology
Stefan W Ryter, Kevin C Ma, Augustine M K Choi
Carbon monoxide (CO) is an endogenously produced gas that has gained recognition as a biological signal transduction effector with properties similar, but not identical, to that of nitric oxide (NO). CO, which binds primarily to heme iron, may activate the hemoprotein guanylate cyclase (sGC), although with lower potency than NO. Furthermore, CO can modulate the activities of several cellular signaling molecules such as p38 MAPK, ERK1/2, JNK, AKT, NF-κB, and others. Emerging studies suggest that mitochondria, the energy-generating organelle of cells, represent a key target of CO action in eukaryotes...
November 8, 2017: American Journal of Physiology. Cell Physiology
Eric Delpire, Kirk L Hamilton, Thomas J Hawke, Jeffrey S Isenberg, Sophie Lotersztajn, Jason X-J Yuan, Josephine C Adams
Not applicable for an Editorial.
November 1, 2017: American Journal of Physiology. Cell Physiology
Derek W Stouth, Alexander Manta, Vladimir Ljubicic
Protein arginine methyltransferase 1 (PRMT1), PRMT4, and PRMT5 catalyze the methylation of arginine residues on target proteins. Previous work suggests that these enzymes regulate skeletal muscle plasticity. However, the function of PRMTs during disuse-induced muscle remodelling is unknown. The purpose of our study was to determine whether denervation-induced muscle disuse alters PRMT expression and activity in skeletal muscle, as well as to contextualize PRMT biology within the early disuse-evoked events that precede atrophy, which remain largely undefined...
November 1, 2017: American Journal of Physiology. Cell Physiology
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