Am J Physiol Cell Physiol Watch the video to learn how APS reaches out to developing nations.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Cell Physiol 286: C1-C7, 2004; doi:10.1152/ajpcell.00059.2003
0363-6143/04 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (17)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kan, H.
Right arrow Articles by Finkel, M. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kan, H.
Right arrow Articles by Finkel, M. S.

RECEPTORS AND SIGNAL TRANSDUCTION

p38 MAP kinase-mediated negative inotropic effect of HIV gp120 on cardiac myocytes

Hong Kan,1,2 Zirong Xie,1 and Mitchell S. Finkel1,2,3

Departments of 1Medicine and 2Physiology and Pharmacology, West Virginia University School of Medicine, Robert C. Byrd Health Sciences Center, Morgantown 26506; and 3Louis A. Johnson Department of Veterans Affairs Medical Center, Clarksburg, West Virginia 26301

Submitted 11 February 2003 ; accepted in final form 19 August 2003

Myocardial dysfunction leading to dilated cardiomyopathy has been documented with surprisingly high frequency in human immunodeficiency virus (HIV)-infected individuals. p38 MAP kinase has been implicated as a mediator of myocardial dysfunction. We previously reported p38 MAP kinase activation by the HIV coat protein gp120 in neonatal rat cardiac myocytes. We now report the direct inotropic effects of HIV gp120 on adult rat ventricular myocytes (ARVM). ARVM were continuously superfused with gp120, and percent fractional shortening (FS) was determined by automated border detection and simultaneous intracellular ionized free Ca2+ concentration ([Ca2+]i) measured by fura 2-AM fluorescence: gp120 alone increased FS and increased [Ca2+]i within 5 min and then depressed FS without a decrease in [Ca2+]i by 20–60 min, which persisted for at least 2 h. Exposure of ARVM to gp120 also resulted in the phosphorylation of the upstream regulator of p38 MAP kinase MKK3/6, p38 MAP kinase itself, and its downstream effector, ATF-2, over a similar time course. ERK (p44/42) and JNK stress signaling pathways were not similarly activated. The effects of the p38 MAP kinase inhibitor were concentration dependent. SB-203580 (10 µM) blocked both p38 MAP kinase phosphorylation and the delayed negative inotropic effect of gp120. SB-203580 (5 µM) selectively blocked phosphorylation of ATF-2 without blocking the phosphorylation of MKK3/6 or p38 MAP kinase itself. SB-203580 (5 µM) administered before, with, or after gp120 blocked the negative inotropic effect of gp120 in ARVM. p38 MAP kinase activation may be a common stress-response mechanism contributing to myocardial dysfunction in HIV and other nonischemic as well as ischemic cardiomyopathies.

cardiomyopathy; cell signaling


Address for reprint requests and other correspondence: M. S. Finkel, Dept. of Medicine, WVU Cardiology, Medical Center Dr., Morgantown, WV 26506-9157 (E-mail: mfinkel{at}hsc.wvu.edu).




This article has been cited by other articles:


Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
J.-B. Shen, R. Shutt, A. Pappano, and B. T. Liang
Characterization and mechanism of P2X receptor-mediated increase in cardiac myocyte contractility
Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H3056 - H3062.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
K. Urayama, C. Guilini, N. Messaddeq, K. Hu, M. Steenman, H. Kurose, G. Ert, and C. G. Nebigil
The prokineticin receptor-1 (GPR73) promotes cardiomyocyte survival and angiogenesis
FASEB J, September 1, 2007; 21(11): 2980 - 2993.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
M. Bellahcene, S. Jacquet, X. B. Cao, M. Tanno, R. S. Haworth, J. Layland, A. M. Kabir, M. Gaestel, R. J. Davis, R. A. Flavell, et al.
Activation of p38 Mitogen-Activated Protein Kinase Contributes to the Early Cardiodepressant Action of Tumor Necrosis Factor
J. Am. Coll. Cardiol., August 1, 2006; 48(3): 545 - 555.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
A. Sabri and P. A. Lucchesi
ANG II and cardiac myocyte contractility: p38 is not stressed out!
Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H72 - H73.
[Full Text] [PDF]

Home page
 J. Virol.Home page
D. Hargett, T. McLean, and S. L. Bachenheimer
Herpes Simplex Virus ICP27 Activation of Stress Kinases JNK and p38
J. Virol., July 1, 2005; 79(13): 8348 - 8360.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
T. Sumida, H. Otani, S. Kyoi, T. Okada, H. Fujiwara, Y. Nakao, M. Kido, and H. Imamura
Temporary blockade of contractility during reperfusion elicits a cardioprotective effect of the p38 MAP kinase inhibitor SB-203580
Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2726 - H2734.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
H. Kan, D. Birkle, A. C. Jain, C. Failinger, S. Xie, and M. S. Finkel
p38 MAP kinase inhibitor reverses stress-induced cardiac myocyte dysfunction
J Appl Physiol, January 1, 2005; 98(1): 77 - 82.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2004 by the American Physiological Society.