(Circulation. 1997;96:1937-1943.)
© 1997 American Heart Association, Inc.
Articles |
Chronic Hypoxia Modulates the Interleukin-1ß–Stimulated Inducible Nitric Oxide Synthase Pathway in Cardiac Myocytes
From the Cardiology Section of the Veterans Affairs Medical Center, the Cardiovascular Research Institute, and the Department of Medicine, University of California, San Francisco.
Correspondence to Dr Joel S. Karliner, Chief, Cardiology Section, VA Medical Center, 4150 Clement St, San Francisco, CA 94121. E-mail karliner.joel-s{at}sanfrancisco.va.gov
Background We wished to determine whether the cytokine-inducible nitric oxide synthase (iNOS) pathway is modulated by chronic hypoxia in vitro.
Methods and Results We investigated the effects of the
proinflammatory cytokine interleukin (IL)-1ß on expression of
iNOS mRNA, iNOS protein, and NO production in cultured neonatal
rat cardiomyocytes subjected to 1% O2 for 48
hours. Among several cytokines tested, IL-1ß was the most
effective in stimulating NO production, which was maximum at 48
hours. In parallel, IL-1ß induced expression of both iNOS mRNA and
protein. Hypoxia alone had no effect on NO production,
iNOS gene expression, or protein induction. However, chronic
hypoxia decreased IL-1ß–stimulated NO production,
mRNA expression, and protein level in cardiac myocytes.
Radioligand binding and electrophoretic mobility shift
assays showed that during chronic hypoxia, IL-1 receptor
density and activity of the transcription factor NF-
B induced by
IL-1ß were decreased, which may account at least in part for the
decrease in iNOS expression.
Conclusions These data indicate that IL-1ß induces iNOS gene expression, de novo synthesis of iNOS protein, and NO generation in neonatal rat cardiomyocytes and that chronic hypoxia appears to be a potent negative regulator of iNOS expression in these cells.
Key Words: interleukins • nitric oxide synthase • signal transduction • hypoxia
This article has been cited by other articles:
 |
|
 |
|
  A. Degrossoli and S. Giorgio Functional Alterations in Macrophages After Hypoxia Selection Exp Biol Med, January 1, 2007; 232(1): 88 - 95. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Tatsumi, J. Shiraishi, N. Keira, K. Akashi, A. Mano, S. Yamanaka, S. Matoba, S. Fushiki, H. Fliss, and M. Nakagawa Intracellular ATP is required for mitochondrial apoptotic pathways in isolated hypoxic rat cardiac myocytes Cardiovasc Res, August 1, 2003; 59(2): 428 - 440. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Wright, J. J. Higgin, R. T. Raines, C. Steenbergen, and E. Murphy Activation of the Prolyl Hydroxylase Oxygen-sensor Results in Induction of GLUT1, Heme Oxygenase-1, and Nitric-oxide Synthase Proteins and Confers Protection from Metabolic Inhibition to Cardiomyocytes J. Biol. Chem., May 23, 2003; 278(22): 20235 - 20239. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Kacimi and A. M. Gerdes Alterations in G Protein and MAP Kinase Signaling Pathways During Cardiac Remodeling in Hypertension and Heart Failure Hypertension, April 1, 2003; 41(4): 968 - 977. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Heineke, T. Kempf, T. Kraft, A. Hilfiker, H. Morawietz, R. J. Scheubel, P. Caroni, S. M. Lohmann, H. Drexler, and K. C. Wollert Downregulation of Cytoskeletal Muscle LIM Protein by Nitric Oxide: Impact on Cardiac Myocyte Hypertrophy Circulation, March 18, 2003; 107(10): 1424 - 1432. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. R. Pitt and C. M. St. Croix Complex Regulation of iNOS in Lung Am. J. Respir. Cell Mol. Biol., January 1, 2002; 26(1): 6 - 9. [Full Text] [PDF]
|
|
|
|
|
|
J. J. Zulueta, R. Sawhney, U. Kayyali, M. Fogel, C. Donaldson, H. Huang, J. J. Lanzillo, and P. M. Hassoun Modulation of Inducible Nitric Oxide Synthase by Hypoxia in Pulmonary Artery Endothelial Cells Am. J. Respir. Cell Mol. Biol., January 1, 2002; 26(1): 22 - 30. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Ferreiro, A. C. P. Chagas, M. H. C. Carvalho, A. P. Dantas, M. B. Jatene, L. C. Bento de Souza, and P. Lemos da Luz Influence of Hypoxia on Nitric Oxide Synthase Activity and Gene Expression in Children With Congenital Heart Disease : A Novel Pathophysiological Adaptive Mechanism Circulation, May 8, 2001; 103(18): 2272 - 2276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Otto and J. E. Baumgardner Effect of culture PO2 on macrophage (RAW 264.7) nitric oxide production Am J Physiol Cell Physiol, February 1, 2001; 280(2): C280 - C287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Marin-Garcia, M. J Goldenthal, and G. W Moe Mitochondrial pathology in cardiac failure Cardiovasc Res, January 1, 2001; 49(1): 17 - 26. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kan, Z. Xie, and M. S. Finkel HIV gp120 enhances NO production by cardiac myocytes through p38 MAP kinase-mediated NF-kappa B activation Am J Physiol Heart Circ Physiol, December 1, 2000; 279(6): H3138 - H3143. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Kacimi, J. Chentoufi, N. Honbo, C. S. Long, and J. S. Karliner Hypoxia differentially regulates stress proteins in cultured cardiomyocytes: Role of the p38 stress-activated kinase signaling cascade, and relation to cytoprotection Cardiovasc Res, April 1, 2000; 46(1): 139 - 150. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Jung, L. A. Palmer, N. Zhou, and R. A. Johns Hypoxic Regulation of Inducible Nitric Oxide Synthase via Hypoxia Inducible Factor-1 in Cardiac Myocytes Circ. Res., February 18, 2000; 86(3): 319 - 325. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. KAKOKI, Y. HIRATA, H. HAYAKAWA, E. SUZUKI, D. NAGATA, A. TOJO, H. NISHIMATSU, N. NAKANISHI, Y. HATTORI, K. KIKUCHI, et al. Effects of Tetrahydrobiopterin on Endothelial Dysfunction in Rats with Ischemic Acute Renal Failure J. Am. Soc. Nephrol., February 1, 2000; 11(2): 301 - 309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. He and M. C. LaPointe Interleukin-1{beta} Regulates the Human Brain Natriuretic Peptide Promoter via Ca2+-Dependent Protein Kinase Pathways Hypertension, January 1, 2000; 35(1): 292 - 296. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kan, Z. Xie, and M. S. Finkel TNF-alpha enhances cardiac myocyte NO production through MAP kinase-mediated NF-kappa B activation Am J Physiol Heart Circ Physiol, October 1, 1999; 277(4): H1641 - H1646. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sasayama, A. Matsumori, and Y. Kihara New insights into the pathophysiological role for cytokines in heart failure Cardiovasc Res, June 1, 1999; 42(3): 557 - 564. [Full Text] [PDF]
|
|
|
|
|
|
Q. He and M. C. LaPointe Interleukin-1ß Regulation of the Human Brain Natriuretic Peptide Promoter Involves Ras-, Rac-, and p38 Kinase–Dependent Pathways in Cardiac Myocytes Hypertension, January 1, 1999; 33(1): 283 - 289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Koudssi, J. E. Lopez, S. Villegas, and C. S. Long Cardiac Fibroblasts Arrest at the G1/S Restriction Point in Response to Interleukin (IL)-1beta . EVIDENCE FOR IL-1beta -INDUCED HYPOPHOSPHORYLATION OF THE RETINOBLASTOMA PROTEIN J. Biol. Chem., October 2, 1998; 273(40): 25796 - 25803. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A.M. Norman, M. H. Yacoub, and P. J.R. Barton Nuclear factor NF-{kappa}B in myocardium: developmental expression of subunits and activation by interleukin-1{beta} in cardiac myocytes in vitro Cardiovasc Res, August 1, 1998; 39(2): 434 - 441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Kacimi, J. S. Karliner, F. Koudssi, and C. S. Long Expression and Regulation of Adhesion Molecules in Cardiac Cells by Cytokines : Response to Acute Hypoxia Circ. Res., March 23, 1998; 82(5): 576 - 586. [Abstract] [Full Text] [PDF]
|
|