DOCSLIB.ORG

Caveolin-1 Expression by Means of P38β Mitogen-Activated Protein

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Caveolin-1 Expression by Means of P38β Mitogen-Activated Protein Corrections PHARMACOLOGY. For the article ‘‘5-Methyltetrahydrofolate and 2005; 10.1073͞pnas.0408919102), the authors note that previ- tetrahydrobiopterin can modulate electrotonically mediated ously published data had been included in error. Specifically, endothelium-dependent vascular relaxation,’’ by Tudor M. in Fig. 3A of the PNAS article, representative traces of the Griffith, Andrew T. Chaytor, Linda M. Bakker, and David H. endothelial cell patch clamp data were identical to those in Edwards, which appeared in issue 19, May 10, 2005, of Proc. figure 2A of ref. 4. The corrected figure and its legend appear Natl. Acad. Sci. USA (102, 7008–7013; first published May 2, below. 4. Chaytor, A. T., Bakker, L. M., Edwards, D. H. & Griffith, T. M. (2005) Br. J. Pharmacol. 144, 108–114. Fig. 3. Electrophysiological studies with connexin-mimetic peptides. (A) Whole-cell patch-clamp recordings and histogram confirming that 600 ␮M 37,40Gap 26 and 100 ␮M 43Gap 26 did not depress endothelial hyperpolarizations evoked by 30 ␮M CPA. (B and C) Original recordings and histograms comparing the effects of the peptides and 2,000 units͞ml catalase on subintimal (B) and subadventitial (C) hyperpolarizations evoked by CPA. 37,40Gap 26 attenuated the transmission of endothelial hyperpolarization to subintimal smooth muscle, whereas 43Gap 26 selectively impaired transmission of subintimal hyperpolarization across the 37,40 vessel wall. The effects of both peptides were prevented by 100 ␮M 5-MTHF and (6R)-BH4 but not by 100 ␮MFAorBH2. Catalase prevented the effects of Gap 26 on subintimal hyperpolarization, but not those of 43Gap 26 on subadventitial hyperpolarization. *, P Ͻ 0.05, compared with control. www.pnas.org͞cgi͞doi͞10.1073͞pnas.0505943102 12644–12645 ͉ PNAS ͉ August 30, 2005 ͉ vol. 102 ͉ no. 35 www.pnas.org Downloaded by guest on September 30, 2021 CELL BIOLOGY. For the article ‘‘Caveolin-1 expression by means of p38␤ mitogen-activated protein kinase mediates the antiprolif- erative effect of carbon monoxide,’’ by Hong Pyo Kim, Xue Wang, Atsunori Nakao, Sung Il Kim, Noriko Murase, Mary E. Choi, Stefan W. Ryter, and Augustine M. K. Choi, which appeared in issue 32, August 9, 2005, of Proc. Natl. Acad. Sci. USA (102, 11319–11324; first published July 28, 2005; 10.1073͞ pnas.0501345102), the authors note that the following state- ments should be added to the acknowledgments: ‘‘We thank M. Drab (Max Planck Institute for Molecular Cell Biology and Genetics, Dresden, Germany) for providing the caveolin-1 knockout mice. We thank K. Kuida (Vertex Pharmaceuticals, Boston) and Richard Flavell (Yale University School of Medi- cine, New Haven, CT) for the gifts of p38Ϫ/Ϫ and jnk-1Ϫ/Ϫ mice, respectively.’’ www.pnas.org͞cgi͞doi͞10.1073͞pnas.0506710102 CORRECTIONS PNAS ͉ August 30, 2005 ͉ vol. 102 ͉ no. 35 ͉ 12645 Downloaded by guest on September 30, 2021 Correction CELL BIOLOGY Correction for “Caveolin-1 expression by means of p38β mitogen- activated protein kinase mediates the antiproliferative effect of carbon monoxide,” by Hong Pyo Kim, Xue Wang, Atsunori Nakao, Sung Il Kim, Noriko Murase, Mary E. Choi, Stefan W. Ryter, and Augustine M. K. Choi, which was first published July 28, 2005; 10.1073/pnas.0501345102 (Proc. Natl. Acad. Sci. U.S.A. 102, 11319–11324). The authors note that: “Although the unacknowledged splice was consistent with editorial policies at the time of publication, in the spirit of transparency, we want to alert readers with an ex- planation. It has come to our attention that a splice in the p38β-/- panel of Fig. 6D has raised concerns about our work. While the splice in the p38β-/- panel was acceptable at the time of publica- tion, we acknowledge it is no longer acceptable by current editorial standards. The induction of caveolin-1 protein expression in p38β-/- cells transfected by p38β expression vector compared to vector alone in the Left panel was further validated in the Right panel of Fig. 6D in an independent experiment wherein we observed caveolin- 1 protein induction in the p38β-transfected p38β-/- cells (lane 1) CORRECTION compared to vector pCDNA alone (lane 3) in room air. The con- clusion of Fig. 6 and the paper are not affected by the splice. “Since the publication of this paper in 2005, there have been numerous published papers by other investigators corroborat- ing the discoveries made in this paper that CO is a potent anti- proliferative molecule, and the regulation of p38 pathway by CO. In addition, based on our paper here and others showing the critical role of HO-1/CO and caveolin, biochemists in recent years have demonstrated the physical interaction between caveolin and HO-1, mapping out the specific binding motifs between caveolin scaffolding domain and HO-1.” Published under the PNAS license. Published June 28, 2021. www.pnas.org/cgi/doi/10.1073/pnas.2108491118 PNAS 2021 Vol. 118 No. 27 e2108491118 https://doi.org/10.1073/pnas.2108491118 | 1of1 Caveolin-1 expression by means of p38␤ mitogen-activated protein kinase mediates the antiproliferative effect of carbon monoxide Hong Pyo Kim*, Xue Wang*, Atsunori Nakao†, Sung Il Kim‡, Noriko Murase†, Mary E. Choi‡, Stefan W. Ryter*, and Augustine M. K. Choi*§ *Division of Pulmonary, Allergy, and Critical Care Medicine, †Thomas E. Starzl Transplantation Institute, ‡Renal-Electrolyte Division, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213 Edited by Solomon H. Snyder, Johns Hopkins University School of Medicine, Baltimore, MD, and approved June 24, 2005 (received for review February 16, 2005) During vascular injury, the proliferation and migration of smooth proliferation (18). Despite the well known toxicity of this gas, muscle cells leads to characteristic neointima formation, which can CO potentially acts as a signaling molecule at trace levels in be exacerbated by genetic depletion of caveolin-1 or heme oxy- cellular and biological systems (19). CO arises physiologically genase 1 (HO-1), and inhibited by carbon monoxide (CO), a by- in most cell types during the oxidative catabolism of heme by product of heme oxygenase 1 activity. CO inhibited smooth muscle the heme oxygenase (HO, E.C. 1:14:99:3) enzymes (19). cell proliferation by activating p38 mitogen-activated protein ki- Expression of the inducible isozyme, heme oxygenase-1 nase (MAPK) and p21Waf1/Cip1. Exposure to CO increased caveolin-1 (HO-1) represents a protective response to injury associated expression in neointimal lesions of injured aorta and in vitro by with proapoptotic stimuli or inflammation (20–22). Expres- ؊ ؊ activating guanylyl cyclase and p38 MAPK. p38␤ / fibroblasts did sion of HO-1-inhibited cellular proliferation in pulmonary not induce caveolin-1 in response to CO, and exhibited a dimin- epithelial cells (23) and in vascular SMC in vivo and in vitro, ished basal caveolin-1 expression, which was restored by p38␤ associated with G1͞S growth arrest and up-regulation of gene transfer. p38␤ MAPK down-regulated extracellular signal- p21Waf1/Cip1 (24). CO, when applied exogenously confers po- regulated protein kinase 1͞2 (ERK-1͞2), which can repress caveo- tent antiproliferative effects in airway and vascular SMC, lin-1 transcription. Genetic depletion of caveolin-1 abolished the which depend on cGMP and p38 MAPK (18, 25, 26). antiproliferative effect of CO. Thus, we demonstrate that CO, by In this study, we have further investigated the signaling ␤ activating p38 MAPK, up-regulates caveolin-1, which acts as a pathways that mediate the antiproliferative effects of CO. We tumor suppressor protein that mediates the growth inhibitory show that the activation of the p38␤ MAPK signaling pathway properties of this gas. by CO led to an enhanced expression of caveolin-1 in fibroblasts and SMC, which in turn mediated the increased expression of ctivation of the p38 mitogen-activated protein kinase (MAPK) p21Waf1/Cip1, and the down-regulation of cyclin A, leading to Aby genetic overexpression or cellular stimulation with noxious growth arrest. The inhibition of intimal hyperplasia by CO environmental agents can result in permanent cell cycle arrest and treatment in a vascular injury model involved the enhanced premature cell senescence (1–3). Many cell differentiation pro- expression of caveolin-1 in vascular smooth muscle. We dem- grams also involve the activation of p38 MAPK, including the onstrate that CO failed to inhibit cellular proliferation in the neuronal differentiation of PC12 cells (4), the erythropoietin- absence of caveolin-1 expression, strongly supporting a critical induced differentiation of erythroid precursors (5), as well as role for caveolin-1 in the antiproliferative activity of this gas. C2C12 myogenesis (6), and 3T3-L1 adipogenesis (7). Caveolin-1, which serves as the principle structural compo- Materials and Methods CELL BIOLOGY nent of plasma membrane caveolae, potentially regulates many Materials. Platelet-derived growth factor (PDGF, rat recombi- downstream signaling processes that originate in the membrane nant BB-form) and all other reagent chemicals were from Sigma. (8). Caveolin-1-null mice develop hypercellularity in the lungs, mammary gland, and heart associated with hyperactivation of Cell Culture and Treatments. Primary rat pulmonary artery SMC ͞ ͞ the extracellular regulated kinase-1 2 (ERK1 2) MAPK (9–11). were cultured as described (18) and used for experiments as Interestingly, elevated levels of caveolin-1 appear in senescent subconfluent monolayers at passages 7–12. SMC were grown in cells or in aged animals (12, 13), and in fully differentiated cells, DMEM high glucose media containing 10% FBS and antibiotics. such as endothelial cells, epithelial cells, fibroblasts, and adipo- Ϫ/Ϫ Fibroblasts were cultured from the lungs of p38␤ , c-Jun-NH2- cytes (13). On the other hand, caveolin-1 seems down-regulated terminal kinase Ϫ͞Ϫ (JnkϪ/Ϫ), or caveolin-1-null (cavϪ/Ϫ) mice in human tumors, in cell lines derived from human tumors, and as described (27). Cells were grown in humidified incubators in oncogene-transformed cell lines (i.e., H-Ras and v-Abl) (14, containing an atmosphere of 5% CO2 and 95% air at 37°C.
Load more

Recommended publications
  • Identi®Cation and Role of Adenylyl Cyclase in Auxin Signalling in Higher
    letters to nature + + + P.P. thank the Academy of Finland and the Deutsche Forschungsgemeinschaft, respectively, for ®nancial CO , 53), 77 (C6H5 , 60), 73 (TMSi , 84); 6-methyl-4-hydroxy-2-pyrone: RRt 0.35, 198 (M+, 18), 183 ([M-Me]+, 16), 170 ([M-CO]+, 54), 155 ([M-CO-Me]+, support. + + Correspondence and requests for materials should be addressed to J.S. (e-mail: [email protected] 15), 139 ([M-Me-CO2] , 10), 127 ([M-Me-2CO] , 13), 99 (12), 84 (13), 73 + + freiburg.de). (TMSi , 100), 43 (CH3CO , 55). The numbers show m/z values, and the key fragments and their relative intensities are indicated in parentheses. Received 4 August; accepted 14 October 1998. erratum 1. Helariutta, Y. et al. Chalcone synthase-like genes active during corolla development are differentially expressed and encode enzymes with different catalytic properties in Gerbera hybrida (Asteraceae). Plant Mol. Biol. 28, 47±60 (1995). 2. Helariutta, Y. et al. Duplication and functional divergence in the chalcone synthase gene family of 8 Asteraceae: evolution with substrate change and catalytic simpli®cation. Proc. Natl Acad. Sci. USA 93, Crystal structure of the complex 9033±9038 (1996). 3. Thaisrivongs, S. et al. Structure-based design of HIV protease inhibitors: 5,6-dihydro-4-hydroxy-2- of the cyclin D-dependent pyrones as effective, nonpeptidic inhibitors. J. Med. Chem. 39, 4630±4642 (1996). 4. Hagen, S. E. et al. Synthesis of 5,6-dihydro-4-hydroxy-2-pyrones as HIV-1 protease inhibitors: the kinase Cdk6 bound to the profound effect of polarity on antiviral activity. J. Med. Chem.
    [Show full text]
  • Soluble Guanylate Cyclase and Cgmp-Dependent Protein Kinase I Expression in the Human Corpus Cavernosum
    International Journal of Impotence Research (2000) 12, 157±164 ß 2000 Macmillan Publishers Ltd All rights reserved 0955-9930/00 $15.00 www.nature.com/ijir Soluble guanylate cyclase and cGMP-dependent protein kinase I expression in the human corpus cavernosum T Klotz1*, W Bloch2, J Zimmermann1, P Ruth3, U Engelmann1 and K Addicks2 1Department of Urology, University of Cologne; 2Institute I of Anatomy, University of Cologne; and 3Institute of Pharmacology, TU University of Munich, Germany Nitric oxide (NO) as a mediator in smooth muscle cells causes rapid and robust increases in cGMP levels. The cGMP-dependent protein kinase I has emerged as an important signal transduction mediator for smooth muscle relaxation. The purpose of this study was to examine the existence and distribution of two key enzymes of the NO=cGMP pathway, the cGMP-dependent kinase I (cGK I) and the soluble guanylate cyclase (sGC) in human cavernosal tissue. The expression of the enzymes were examined in corpus cavernosum specimens of 23 patients. Eleven potent patients suffered from penile deviations and were treated via Nesbit's surgical method. Nine long-term impotent patients underwent implantation of ¯exible hydraulic prothesis. Three potent patients underwent trans-sexual operations. Expression of the sGC and cGK I were examined immunohistochemically using speci®c antibodies. In all specimens of cavernosal tissue a distinct immunoreactivity was observed in different parts and structures. We found a high expression of sGC and cGK I in smooth muscle cells of vessels and in the ®bromuscular stroma. The endothelium of the cavernosal sinus, of the cavernosal arteries, and the cavernosal nerve ®bers showed an immunoreactivity against sGC.
    [Show full text]
  • Soluble Guanylate Cyclase B1-Subunit Expression Is Increased in Mononuclear Cells from Patients with Erectile Dysfunction
    International Journal of Impotence Research (2006) 18, 432–437 & 2006 Nature Publishing Group All rights reserved 0955-9930/06 $30.00 www.nature.com/ijir ORIGINAL ARTICLE Soluble guanylate cyclase b1-subunit expression is increased in mononuclear cells from patients with erectile dysfunction PJ Mateos-Ca´ceres1, J Garcia-Cardoso2, L Lapuente1, JJ Zamorano-Leo´n1, D Sacrista´n1, TP de Prada1, J Calahorra2, C Macaya1, R Vela-Navarrete2 and AJ Lo´pez-Farre´1 1Cardiovascular Research Unit, Cardiovascular Institute, Hospital Clı´nico San Carlos, Madrid, Spain and 2Urology Department, Fundacio´n Jime´nez Diaz, Madrid, Spain The aim was to determine in circulating mononuclear cells from patients with erectile dysfunction (ED), the level of expression of endothelial nitric oxide synthase (eNOS), soluble guanylate cyclase (sGC) b1-subunit and phosphodiesterase type-V (PDE-V). Peripheral mononuclear cells from nine patients with ED of vascular origin and nine patients with ED of neurological origin were obtained. Fourteen age-matched volunteers with normal erectile function were used as control. Reduction in eNOS protein was observed in the mononuclear cells from patients with ED of vascular origin but not in those from neurological origin. Although sGC b1-subunit expression was increased in mononuclear cells from patients with ED, the sGC activity was reduced. However, only the patients with ED of vascular origin showed an increased expression of PDE-V. This work shows for the first time that, independently of the aetiology of ED, the expression of sGC b1-subunit was increased in circulating mononuclear cells; however, the expression of both eNOS and PDE-V was only modified in the circulating mononuclear cells from patients with ED of vascular origin.
    [Show full text]
  • Looking for New Classes of Bronchodilators
    REVIEW BRONCHODILATORS The future of bronchodilation: looking for new classes of bronchodilators Mario Cazzola1, Paola Rogliani 1 and Maria Gabriella Matera2 Affiliations: 1Dept of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy. 2Dept of Experimental Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy. Correspondence: Mario Cazzola, Dept of Experimental Medicine, University of Rome Tor Vergata, Via Montpellier 1, Rome, 00133, Italy. E-mail: [email protected] @ERSpublications There is a real interest among researchers and the pharmaceutical industry in developing novel bronchodilators. There are several new opportunities; however, they are mostly in a preclinical phase. They could better optimise bronchodilation. http://bit.ly/2lW1q39 Cite this article as: Cazzola M, Rogliani P, Matera MG. The future of bronchodilation: looking for new classes of bronchodilators. Eur Respir Rev 2019; 28: 190095 [https://doi.org/10.1183/16000617.0095-2019]. ABSTRACT Available bronchodilators can satisfy many of the needs of patients suffering from airway disorders, but they often do not relieve symptoms and their long-term use raises safety concerns. Therefore, there is interest in developing new classes that could help to overcome the limits that characterise the existing classes. At least nine potential new classes of bronchodilators have been identified: 1) selective phosphodiesterase inhibitors; 2) bitter-taste receptor agonists; 3) E-prostanoid receptor 4 agonists; 4) Rho kinase inhibitors; 5) calcilytics; 6) agonists of peroxisome proliferator-activated receptor-γ; 7) agonists of relaxin receptor 1; 8) soluble guanylyl cyclase activators; and 9) pepducins. They are under consideration, but they are mostly in a preclinical phase and, consequently, we still do not know which classes will actually be developed for clinical use and whether it will be proven that a possible clinical benefit outweighs the impact of any adverse effect.
    [Show full text]
  • Nitric Oxide Activates Guanylate Cyclase and Increases Guanosine 3':5'
    Proc. Natl. Acad. Sci. USA Vol. 74, No. 8, pp. 3203-3207, August 1977 Biochemistry Nitric oxide activates guanylate cyclase and increases guanosine 3':5'-cyclic monophosphate levels in various tissue preparations (nitro compounds/adenosine 3':5'-cyclic monophosphate/sodium nitroprusside/sodium azide/nitrogen oxides) WILLIAM P. ARNOLD, CHANDRA K. MITTAL, SHOJI KATSUKI, AND FERID MURAD Division of Clinical Pharmacology, Departments of Medicine, Pharmacology, and Anesthesiology, University of Virginia, Charlottesville, Virginia 22903 Communicated by Alfred Gilman, May 16, 1977 ABSTRACT Nitric oxide gas (NO) increased guanylate cy- tigation of this activation. NO activated all crude and partially clase [GTP pyrophosphate-yase (cyclizing), EC 4.6.1.21 activity purified guanylate cyclase preparations examined. It also in- in soluble and particulate preparations from various tissues. The effect was dose-dependent and was observed with all tissue creased cyclic GMP but not adenosine 3':5'-cyclic monophos- preparations examined. The extent of activation was variable phate (cyclic AMP) levels in incubations of minces from various among different tissue preparations and was greatest (19- to rat tissues. 33-fold) with supernatant fractions of homogenates from liver, lung, tracheal smooth muscle, heart, kidney, cerebral cortex, and MATERIALS AND METHODS cerebellum. Smaller effects (5- to 14-fold) were observed with supernatant fractions from skeletal muscle, spleen, intestinal Male Sprague-Dawley rats weighing 150-250 g were decapi- muscle, adrenal, and epididymal fat. Activation was also ob- tated. Tissues were rapidly removed, placed in cold 0.-25 M served with partially purified preparations of guanylate cyclase. sucrose/10 mM Tris-HCl buffer (pH 7.6), and homogenized Activation of rat liver supernatant preparations was augmented in nine volumes of this solution by using a glass homogenizer slightly with reducing agents, decreased with some oxidizing and Teflon pestle at 2-4°.
    [Show full text]
  • A Nitric Oxide/Cysteine Interaction Mediates the Activation of Soluble Guanylate Cyclase
    A nitric oxide/cysteine interaction mediates the activation of soluble guanylate cyclase Nathaniel B. Fernhoffa,1, Emily R. Derbyshirea,1,2, and Michael A. Marlettaa,b,c,3 Departments of aMolecular and Cell Biology and bChemistry, University of California, Berkeley, CA 94720; and cCalifornia Institute for Quantitative Biosciences and Division of Physical Biosciences, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 Contributed by Michael A. Marletta, October 1, 2009 (sent for review August 22, 2009) Nitric oxide (NO) regulates a number of essential physiological pro- high activity of the xsNO state rapidly reverts to the low activity of cesses by activating soluble guanylate cyclase (sGC) to produce the the 1-NO state. Thus, all three sGC states (basal, 1-NO, and xsNO) second messenger cGMP. The mechanism of NO sensing was previ- can be prepared and studied in vitro (7, 8). Importantly, these ously thought to result exclusively from NO binding to the sGC heme; results define two different states of purified sGC with heme bound however, recent studies indicate that heme-bound NO only partially NO (7, 8), one with a high activity and one with a low activity. activates sGC and additional NO is involved in the mechanism of Further evidence for a non-heme NO binding site was obtained maximal NO activation. Furthermore, thiol oxidation of sGC cysteines by blocking the heme site with the tight-binding ligand butyl results in the loss of enzyme activity. Herein the role of cysteines in isocyanide, and then showing that NO still activated the enzyme NO-stimulated sGC activity investigated. We find that the thiol mod- (14).
    [Show full text]
  • Biosignaling-2014.Pdf
    Biosignaling Principals of Biochemistry, Lehninger, Chap 12 CBIO7100 Su Dharmawardhane [email protected] Lecture Outline } Introduction: Importance of cell signaling to periodontal disease } Principals of signal transduction, adaptors } G protein coupled receptors, Chemokine receptors } Receptor tyrosine kinases } Inflammatory signaling: Toll like receptor signaling and the role of NfκB in periodontitis } Receptor guanylyl kinases } Hormone receptors INTRODUCTION } Why do I have to learn about signaling? I am going to be a dentist Signaling is central to teeth development and decay. Signaling is important in periodontal disease. Periodontal Disease (Gum Disease) } Periodontal disease is inflammation and infection that destroys the tissues that support the teeth, including the gums, the periodontal ligaments, and the tooth sockets (alveolar bone). } Gingivitis: inflammation of the gums due to bacteria. Signaling molecules produced by bacteria activate receptors on periodontal cells to ultimately destroy periodontal tissue. } Although periodontal disease is initiated by bacteria that colonize the tooth surface and ginigva, the host signaling response is essential for breakdown of bone and connective tissue: Osteoclastogenesis and bone resorption. } Periodontal infection requires expression of a number of signaling molecules: proinflammatory and antiinflammatory cytokines, growth factors, etc. Cell signaling in periodontal disease u de Souza, et al. 2012. Modulation of host cell signaling pathways as a therapeutic approach in periodontal disease. Appl. Oral Sci. 20:128-138. Pharmacological inhibitors of MAPK, NFκB and JAK/STAT pathways are being developed to manage periodontal disease. u Kirkwood, et al., Novel host response therapeutic approaches to treat periodontal diseases. Periodontol 2000. 2007 ; 43: 294–315. Periodontal disease initiation and progression occurs as a consequence of the host immune inflammatory response to oral pathogens.
    [Show full text]
  • New Insights Into the Role of Soluble Guanylate Cyclase in Blood Pressure Regulation
    New insights into the role of soluble guanylate cyclase in blood pressure regulation The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Buys, Emmanuel, and Patrick Sips. 2014. New Insights into the Role of Soluble Guanylate Cyclase in Blood Pressure Regulation. Current Opinion in Nephrology and Hypertension 23, no. 2: 135–142. doi:10.1097/01.mnh.0000441048.91041.3a. Published Version doi:10.1097/01.mnh.0000441048.91041.3a Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:29731915 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA NIH Public Access Author Manuscript Curr Opin Nephrol Hypertens. Author manuscript; available in PMC 2015 March 01. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Curr Opin Nephrol Hypertens. 2014 March ; 23(2): 135–142. doi:10.1097/01.mnh.0000441048.91041.3a. New Insights into the Role of Soluble Guanylate Cyclase in Blood Pressure Regulation Emmanuel Buys1 and Patrick Sips2 1Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA 2Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Abstract Purpose of review—Nitric oxide (NO) – soluble guanylate cyclase (sGC)-dependent signaling mechanisms have a profound effect on the regulation of blood pressure.
    [Show full text]
  • Metabolic Phenotyping of Murine Hearts Overexpressing Constitutively Active Soluble Guanylate Cyclase
    METABOLIC PHENOTYPING OF MURINE HEARTS OVEREXPRESSING CONSTITUTIVELY ACTIVE SOLUBLE GUANYLATE CYCLASE Ramzi Khairallah Department of Experimental Medicine Faculty of Medicine McGill University, Montreal Quebec, Canada A thesis submitted to McGill University in partial fulfillment of the requirements of the degree of Master’s in Science August 2007 ©Ramzi Khairallah, 2007 1 Table of Contents Table of Contents .......................................................................................................................................... 2 Abstract ......................................................................................................................................................... 5 Résumé ......................................................................................................................................................... 6 Acknowledgments ......................................................................................................................................... 7 Chapter I ‐ Introduction ................................................................................................................................ 8 Cardiac hypertrophy and its progression to failure .................................................................................. 8 Molecular pathways leading to cardiomyocyte hypertrophy ............................................................. 11 Calcineurin‐ Nuclear Factor of Activated T‐cells (NFAT) signaling .................................................
    [Show full text]
  • Non-Canonical Chemical Feedback Self-Limits Nitric Oxide-Cyclic GMP Signaling in Health and Disease Vu Thao-Vi Dao1,2,9, Mahmoud H
    www.nature.com/scientificreports OPEN Non-canonical chemical feedback self-limits nitric oxide-cyclic GMP signaling in health and disease Vu Thao-Vi Dao1,2,9, Mahmoud H. Elbatreek1,3,9 ✉ , Martin Deile4, Pavel I. Nedvetsky5, Andreas Güldner6, César Ibarra-Alvarado7, Axel Gödecke8 & Harald H. H. W. Schmidt1 ✉ Nitric oxide (NO)-cyclic GMP (cGMP) signaling is a vasoprotective pathway therapeutically targeted, for example, in pulmonary hypertension. Its dysregulation in disease is incompletely understood. Here we show in pulmonary artery endothelial cells that feedback inhibition by NO of the NO receptor, the cGMP forming soluble guanylate cyclase (sGC), may contribute to this. Both endogenous NO from endothelial NO synthase and exogenous NO from NO donor compounds decreased sGC protein and activity. This efect was not mediated by cGMP as the NO-independent sGC stimulator, or direct activation of cGMP- dependent protein kinase did not mimic it. Thiol-sensitive mechanisms were also not involved as the thiol-reducing agent N-acetyl-L-cysteine did not prevent this feedback. Instead, both in-vitro and in- vivo and in health and acute respiratory lung disease, chronically elevated NO led to the inactivation and degradation of sGC while leaving the heme-free isoform, apo-sGC, intact or even increasing its levels. Thus, NO regulates sGC in a bimodal manner, acutely stimulating and chronically inhibiting, as part of self-limiting direct feedback that is cGMP independent. In high NO disease conditions, this is aggravated but can be functionally recovered in a mechanism-based manner by apo-sGC activators that re-establish cGMP formation. Te nitric oxide (NO)-cGMP signaling pathway plays several essential roles in physiology, including cardio- pulmonary homeostasis1,2.
    [Show full text]
  • Identification of the Molecular Basis of Anti-Fibrotic Effects of Soluble Guanylate Cyclase Activator Using the Human Lung Fibroblast
    https://www.scientificarchives.com/journal/archives-of-proteomics-and-bioinformatics Archives of Proteomics and Bioinformatics Research Article Identification of the Molecular Basis of Anti-fibrotic Effects of Soluble Guanylate Cyclase Activator Using the Human Lung Fibroblast Sunhwa Kim1*, Ashmita Saigal1, Weilong Zhao2, Peyvand Amini1, Alex M. Tamburino3, Subharekha Raghavan4, Maarten Hoek5# 1Cardiometabolic Disease Biology-Discovery, Merck & Co., Inc., South San Francisco, CA, USA 2Scientific informatics, Merck & Co., Inc., South San Francisco, CA, USA 3Discovery pGx, Merck & Co., Inc., West Point, PA, USA 4Chemistry Capabilities Accelerate Therapeutics, Merck & Co., Inc., Kenilworth, NJ, USA 5Cardiovascular, Metabolic, Renal, Ophthalmology Biology-Discovery, Merck & Co., Inc., South San Francisco, CA, USA #Present Address: Maze Therapeutics, South San Francisco, CA USA *Correspondence should be addressed to Sunhwa Kim; [email protected] Received date: September 09, 2020, Accepted date: November 11, 2020 Copyright: © 2020 Kim S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Idiopathic pulmonary fibrosis (IPF) is an irreversible and progressive fibrotic lung disease. Advanced IPF patients often demonstrate pulmonary hypertension, which severely impairs patients’ quality of life. The critical physiological roles of soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway have been well characterized in vasodilation and the corresponding therapies and pathway agonists have shown clinical benefits in treating hypertension. In recent years, many preclinical studies have demonstrated anti-fibrotic efficacy of sGC-cGMP activation in various experimental fibrosis models but the molecular basis of the efficacy in these models are not well understood.
    [Show full text]
  • Receptor Guanylyl Cyclases
    Receptor guanylyl cyclases. S K Wong, D L Garbers J Clin Invest. 1992;90(2):299-305. https://doi.org/10.1172/JCI115862. Research Article Three different guanylyl cyclase cell receptors are known, but others will likely be discovered within the next few years. The general function of these receptors appear to relate to the regulation of fluid volume or fluid movement. New receptors, or possibly the currently known receptors, therefore, may be discovered in areas of the body where fluid volume regulation is important. Such fluids whose volume or composition might be regulated by guanylyl cyclase receptors include synovial fluid, uterine/oviductal luminal fluid, follicular fluid, aqueous humor, cerebral spinal fluid, seminiferous tubule luminal fluid, epididymal luminal fluid, seminal plasma, and airway luminal fluid. The function of the heterodimeric forms of guanylyl cyclase appear to relate to a primary regulation of nitric oxide (or similar molecules) concentrations, which are in turn regulated by a Ca2+/calmodulin-sensitive nitric oxide synthase. Find the latest version: https://jci.me/115862/pdf Perspectives Receptor Guanylyl Cyclases Stephen K.-F. Wong and David L. Garbers Department ofPharmacology, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75235 Introduction it therefore remains possible that these forms will closely resem- Cyclic GMP is an intracellular signaling molecule that regu- ble known plasma membrane receptor forms. lates ion channels, cyclic AMP concentrations by virtue of its The second major group of guanylyl cyclases appears to effects on selective phosphodiesterases, and protein kinases to exist as heterodimers containing heme as a prosthetic group alter cellular processes and behavior.
    [Show full text]