Caveolin-1 regulates corneal wound healing by modulating Kir4.1 activity
The expression of caveolin-1 (Cav1) in corneal epithelium is associated with regeneration potency. We used Cav1–/– mice to study the role of Cav1 in modulating corneal wound healing. Western blot and whole cell patch clamp were employed to study the effect of Cav1 deletion on Kir4.1 current density in corneas. We found that Ba2+-sensitive K+ currents in primary cultured murine corneal epithelial cells (pMCE) from Cav1–/– were dramatically reduced (602 pA) compared with those from wild type (WT; 1,300 pA). As a consequence, membrane potential was elevated in pMCE from Cav1–/– compared wit...
Source: AJP: Cell Physiology - June 14, 2016 Category: Cytology Authors: Zhang, C., Su, X., Bellner, L., Lin, D.-H. Tags: CALL FOR PAPERS Source Type: research
PDGF induces SphK1 expression via Egr-1 to promote pulmonary artery smooth muscle cell proliferation
In this study, we investigated the role of platelet-derived growth factor (PDGF), a PAH-relevant stimuli associated with enhanced PASMC proliferation, on SphK1 expression regulation. In human PASMCs (hPASMCs), PDGF significantly increased SphK1 mRNA and protein expression and induced cell proliferation. Selective inhibition of SphK1 attenuated PDGF-induced hPASMC proliferation. In silico promoter analysis for SphK1 identified several binding sites for early growth response protein 1 (Egr-1), a PDGF-associated transcription factor. Luciferase assays demonstrated that PDGF activates the SphK1 promoter in hPASMCs, and truncat...
Source: AJP: Cell Physiology - June 14, 2016 Category: Cytology Authors: Sysol, J. R., Natarajan, V., Machado, R. F. Tags: CALL FOR PAPERS Source Type: research
Chronology of mitochondrial and cellular events during skeletal muscle ischemia-reperfusion
Peripheral artery disease (PAD) is a common circulatory disorder of the lower limb arteries that reduces functional capacity and quality of life of patients. Despite relatively effective available treatments, PAD is a serious public health issue associated with significant morbidity and mortality. Ischemia-reperfusion (I/R) cycles during PAD are responsible for insufficient oxygen supply, mitochondriopathy, free radical production, and inflammation and lead to events that contribute to myocyte death and remote organ failure. However, the chronology of mitochondrial and cellular events during the ischemic period and at the ...
Source: AJP: Cell Physiology - June 14, 2016 Category: Cytology Authors: Paradis, S., Charles, A.-L., Meyer, A., Lejay, A., Scholey, J. W., Chakfe, N., Zoll, J., Geny, B. Tags: REVIEW Source Type: research
Structural ECM components in the premetastatic and metastatic niche
The aim of this review is to give an overview of the extracellular matrix (ECM) components that are important for creating structural changes in the premetastatic and metastatic niche. The successful arrival and survival of cancer cells that have left the primary tumor and colonized distant sites depends on the new microenvironment they encounter. The primary tumor itself releases factors into the circulation that travel to distant organs and then initiate structural changes, both non-enzymatic and enzymatic, to create a favorable niche for the disseminating tumor cells. Therapeutic strategies aimed at targeting cell-ECM i...
Source: AJP: Cell Physiology - June 14, 2016 Category: Cytology Authors: Hoye, A. M., Erler, J. T. Tags: THEMES Source Type: research
Imbalanced Rab3D versus Rab27 increases cathepsin S secretion from lacrimal acini in a mouse model of Sjögren's Syndrome
The mechanism responsible for the altered spectrum of tear proteins secreted by lacrimal gland acinar cells (LGAC) in patients with Sjögren's Syndrome (SS) remains unknown. We have previously identified increased cathepsin S (CTSS) activity as a unique characteristic of tears of patients with SS. Here, we investigated the role of Rab3D, Rab27a, and Rab27b proteins in the enhanced release of CTSS from LGAC. Similar to patients with SS and to the male nonobese diabetic (NOD) mouse model of SS, CTSS activity was elevated in tears of mice lacking Rab3D. Findings of lower gene expression and altered localization of Rab3...
Source: AJP: Cell Physiology - May 31, 2016 Category: Cytology Authors: Meng, Z., Edman, M. C., Hsueh, P.-Y., Chen, C.-Y., Klinngam, W., Tolmachova, T., Okamoto, C. T., Hamm-Alvarez, S. F. Tags: ARTICLES Source Type: research
Interleukin-19 induces angiogenesis in the absence of hypoxia by direct and indirect immune mechanisms
Neovascularization and inflammation are independent biological processes but are linked in response to injury. The role of inflammation-dampening cytokines in the regulation of angiogenesis remains to be clarified. The purpose of this work was to test the hypothesis that IL-19 can induce angiogenesis in the absence of tissue hypoxia and to identify potential mechanisms. Using the aortic ring model of angiogenesis, we found significantly reduced sprouting capacity in aortic rings from IL-19–/– compared with wild-type mice. Using an in vivo assay, we found that IL-19–/– mice respond to vascular endoth...
Source: AJP: Cell Physiology - May 31, 2016 Category: Cytology Authors: Kako, F., Gabunia, K., Ray, M., Kelemen, S. E., England, R. N., Kako, B., Scalia, R. G., Autieri, M. V. Tags: ARTICLES Source Type: research
Regulation of mitogen-activated protein kinase by protein kinase C and mitogen-activated protein kinase phosphatase-1 in vascular smooth muscle
Vascular smooth muscle contraction is primarily regulated by phosphorylation of myosin light chain. There are also modulatory pathways that control the final level of force development. We tested the hypothesis that protein kinase C (PKC) and mitogen-activated protein (MAP) kinase modulate vascular smooth muscle activity via effects on MAP kinase phosphatase-1 (MKP-1). Swine carotid arteries were mounted for isometric force recording and subjected to histamine stimulation in the presence and absence of inhibitors of PKC [bisindolylmaleimide-1 (Bis)], MAP kinase kinase (MEK) (U0126), and MKP-1 (sanguinarine) and flash froze...
Source: AJP: Cell Physiology - May 31, 2016 Category: Cytology Authors: Trappanese, D. M., Sivilich, S., Ets, H. K., Kako, F., Autieri, M. V., Moreland, R. S. Tags: ARTICLES Source Type: research
Functional diversification of sea urchin ABCC1 (MRP1) by alternative splicing
The multidrug resistance protein (MRP) family encodes a diverse repertoire of ATP-binding cassette (ABC) transporters with multiple roles in development, disease, and homeostasis. Understanding MRP evolution is central to unraveling their roles in these diverse processes. Sea urchins occupy an important phylogenetic position for understanding the evolution of vertebrate proteins and have been an important invertebrate model system for study of ABC transporters. We used phylogenetic analyses to examine the evolution of MRP transporters and functional approaches to identify functional forms of sea urchin MRP1 (also known as ...
Source: AJP: Cell Physiology - May 31, 2016 Category: Cytology Authors: Gökirmak, T., Campanale, J. P., Reitzel, A. M., Shipp, L. E., Moy, G. W., Hamdoun, A. Tags: ARTICLES Source Type: research
Caveolin-1 is a checkpoint regulator in hypoxia-induced astrocyte apoptosis via Ras/Raf/ERK pathway
Astrocytes, the most numerous cells in the human brain, play a central role in the metabolic homeostasis following hypoxic injury. Caveolin-1 (Cav-1), a transmembrane scaffolding protein, has been shown to converge prosurvival signaling in the central nerve system. The present study aimed to investigate the role of Cav-1 in the hypoxia-induced astrocyte injury. We also examined how Cav-1 alleviates apoptotic astrocyte death. To this end, primary astrocytes were exposed to oxygen-glucose deprivation (OGD) for 6 h and a subsequent 24-h reoxygenation to mimic hypoxic injury. OGD significantly reduced Cav-1 expression. Downreg...
Source: AJP: Cell Physiology - May 31, 2016 Category: Cytology Authors: Xu, L., Wang, L., Wen, Z., Wu, L., Jiang, Y., Yang, L., Xiao, L., Xie, Y., Ma, M., Zhu, W., Ye, R., Liu, X. Tags: ARTICLES Source Type: research
Cross talk between polysulfide and nitric oxide in rat peritoneal mast cells
The aim of this study was to define the effects of polysulfide on intracellular Ca2+ concentration ([Ca2+]i) and the underlying machinery, especially from the hydrogen sulfide (H2S) and nitric oxide (NO) perspectives, in rat peritoneal mast cells. We found that a polysulfide donor, Na2S4, increased [Ca2+]i, which is both extracellular and intracellular Ca2+ dependent. Intracellular Ca2+ release induced by Na2S4 was attenuated by the addition of a ryanodine receptor blocker. A slow-releasing H2S donor, GYY4137, dose dependently increased [Ca2+]i that was independent from extracellular Ca2+ influx. The GYY4137-induced [Ca2+]...
Source: AJP: Cell Physiology - May 31, 2016 Category: Cytology Authors: Moustafa, A., Habara, Y. Tags: CALL FOR PAPERS Source Type: research
Rab25 influences functional Cav1.2 channel surface expression in arterial smooth muscle cells
Plasma membrane-localized CaV1.2 channels are the primary calcium (Ca2+) influx pathway in arterial smooth muscle cells (myocytes). CaV1.2 channels regulate several cellular functions, including contractility and gene expression, but the trafficking pathways that control the surface expression of these proteins are unclear. Similarly, expression and physiological functions of small Rab GTPases, proteins that control vesicular trafficking in arterial myocytes, are poorly understood. Here, we investigated Rab proteins that control functional surface abundance of CaV1.2 channels in cerebral artery myocytes. Western blotting i...
Source: AJP: Cell Physiology - May 31, 2016 Category: Cytology Authors: Bannister, J. P., Bulley, S., Leo, M. D., Kidd, M. W., Jaggar, J. H. Tags: CALL FOR PAPERS Source Type: research
Activation of mTORC1 by leucine is potentiated by branched-chain amino acids and even more so by essential amino acids following resistance exercise
Protein synthesis is stimulated by resistance exercise and intake of amino acids, in particular leucine. Moreover, activation of mammalian target of rapamycin complex 1 (mTORC1) signaling by leucine is potentiated by the presence of other essential amino acids (EAA). However, the contribution of the branched-chain amino acids (BCAA) to this effect is yet unknown. Here we compare the stimulatory role of leucine, BCAA, and EAA ingestion on anabolic signaling following exercise. Accordingly, eight trained volunteers completed four sessions of resistance exercise during which they ingested either placebo, leucine, BCAA, or EAA...
Source: AJP: Cell Physiology - May 31, 2016 Category: Cytology Authors: Moberg, M., Apro, W., Ekblom, B., van Hall, G., Holmberg, H.-C., Blomstrand, E. Tags: CALL FOR PAPERS Source Type: research
Downregulation of LRRC8A protects human ovarian and alveolar carcinoma cells against Cisplatin-induced expression of p53, MDM2, p21Waf1/Cip1, and Caspase-9/-3 activation
The leucine-rich repeat containing 8A (LRRC8A) protein is an essential component of the volume-sensitive organic anion channel (VSOAC), and using pharmacological anion channel inhibitors (NS3728, DIDS) and LRRC8A siRNA we have investigated its role in development of Cisplatin resistance in human ovarian (A2780) and alveolar (A549) carcinoma cells. In Cisplatin-sensitive cells Cisplatin treatment increases p53-protein level as well as downstream signaling, e.g., expression of p21Waf1/Cip1, Bax, Noxa, MDM2, and activation of Caspase-9/-3. In contrast, Cisplatin-resistant cells do not enter apoptosis, i.e., their p53 and down...
Source: AJP: Cell Physiology - May 31, 2016 Category: Cytology Authors: Sorensen, B. H., Nielsen, D., Thorsteinsdottir, U. A., Hoffmann, E. K., Lambert, I. H. Tags: CALL FOR PAPERS Source Type: research
Simulation of the effects of moderate stimulation/inhibition of the {beta}1-adrenergic signaling system and its components in mouse ventricular myocytes
The β1-adrenergic signaling system is one of the most important protein signaling systems in cardiac cells. It regulates cardiac action potential duration, intracellular Ca2+ concentration ([Ca2+]i) transients, and contraction force. In this paper, a comprehensive experimentally based mathematical model of the β1-adrenergic signaling system for mouse ventricular myocytes is explored to simulate the effects of moderate stimulations of β1-adrenergic receptors (β1-ARs) on the action potential, Ca2+ and Na+ dynamics, as well as the effects of inhibition of protein kinase A (PKA) and phosphodiesterase of typ...
Source: AJP: Cell Physiology - May 31, 2016 Category: Cytology Authors: Grinshpon, M., Bondarenko, V. E. Tags: CALL FOR PAPERS Source Type: research
Synchronized simulation with heart. Focus on "Simulation of the effects of moderate stimulation/inhibition of the {beta}1-adrenergic signaling system and its components in mouse ventricular myocytes"
(Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - May 31, 2016 Category: Cytology Authors: Yamamura, H. Tags: EDITORIAL FOCUS Source Type: research
