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

2004 ◽  
Vol 286 (1) ◽  
pp. C1-C7 ◽  
Author(s):  
Hong Kan ◽  
Zirong Xie ◽  
Mitchell S. Finkel
Keyword(s):  
Map Kinase ◽  
Cardiac Myocytes ◽  
Myocardial Dysfunction ◽  
Negative Inotropic Effect ◽  
P38 Map Kinase ◽  
Neonatal Rat ◽  
Inotropic Effect ◽  
Kinase Activation ◽  
Hiv Gp120 ◽  
Sb 203580

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+]iwithin 5 min and then depressed FS without a decrease in [Ca2+]iby 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.

scholarly journals p38 MAP kinase inhibitor reverses stress-induced myocardial dysfunction in vivo

2009 ◽  
Vol 106 (4) ◽  
pp. 1132-1141 ◽  
Author(s):  
Fangping Chen ◽  
Hong Kan ◽  
Gerry Hobbs ◽  
Mitchell S. Finkel
Keyword(s):  
Map Kinase ◽  
Diastolic Function ◽  
Prenatal Stress ◽  
Intraperitoneal Injection ◽  
Restraint Stress ◽  
Kinase Inhibitor ◽  
Myocardial Dysfunction ◽  
Left Ventricular ◽  
P38 Map Kinase ◽  
Sb 203580

Recent clinical reports strongly support the intriguing possibility that emotional stress alone is sufficient to cause reversible myocardial dysfunction in patients. We previously reported that a combination of prenatal stress followed by restraint stress (PS+R) results in echocardiographic evidence of myocardial dysfunction in anesthetized rats compared with control rats subjected to the same restraint stress (Control+R). We now report results of our catheter-based hemodynamic studies in both anesthetized and freely ambulatory awake rats, comparing PS+R vs. Control+R. Systolic function [positive rate of change in left ventricular pressure over time (+dP/d t)] was significantly depressed ( P < 0.01) in PS+R vs. Control+R both under anesthesia (6,287 ± 252 vs. 7,837 ± 453 mmHg/s) and awake (10,438 ± 741 vs. 12,111 ± 652 mmHg/s). Diastolic function (−dP/d t) was also significantly depressed ( P < 0.05) in PS+R vs. Control+R both under anesthesia (−5,686 ± 340 vs. −7,058 ± 458 mmHg/s) and awake (−8,287 ± 444 vs. 10,440 ± 364 mmHg/s). PS+R also demonstrated a significantly attenuated ( P < 0.05) hemodynamic response to increasing doses of the β-adrenergic agonist isoproterenol. Intraperitoneal injection of the p38 MAP kinase inhibitor SB-203580 reversed the baseline reduction in +dP/d t and −dP/d t as well as the blunted isoproterenol response. Intraperitoneal injection of SB-203580 also reversed p38 MAP kinase and troponin I phosphorylation in cardiac myocytes isolated from PS+R. Thus the combination of prenatal stress followed by restraint stress results in reversible depression in both systolic and diastolic function as well as defective β-adrenergic receptor signaling. Future studies in this animal model may provide insights into the basic mechanisms contributing to reversible myocardial dysfunction in patients with ischemic and nonischemic cardiomyopathies.

scholarly journals HIV GP120 Mediates Negative Inotropic Effect through CXCR4 Receptor on Cardiac Myocytes

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Youxi Yuan ◽  
Hong Kan ◽  
Qiujuan Fang ◽  
Fangping Chen ◽  
Sherry Xie ◽  
...  
Keyword(s):  
Cardiac Myocytes ◽  
Negative Inotropic Effect ◽  
Inotropic Effect ◽  
Cxcr4 Receptor ◽  
Hiv Gp120

SAPKs regulation of ischemic preconditioning

2000 ◽  
Vol 279 (3) ◽  
pp. H901-H907 ◽  
Author(s):  
Motoaki Sato ◽  
Gerald A. Cordis ◽  
Nilanjana Maulik ◽  
Dipak K. Das
Keyword(s):  
Map Kinase ◽  
Map Kinases ◽  
Kinase Inhibitor ◽  
Signal Transduction Pathway ◽  
P38 Map Kinase ◽  
Kinase Activation ◽  
Protein Levels ◽  
Rat Hearts ◽  
Mitogen Activated Protein ◽  
Sb 203580

The role of stress-activated protein kinases (SAPKs), c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase, in preconditioning (PC) was examined with the use of isolated rat hearts subjected to four cyclic episodes of 5-min ischemia and 10-min reperfusion followed by 30-min ischemia and 2-h reperfusion (I/R). A group of hearts was preperfused with 100 μM curcumin, a c-Jun and JNK1 inhibitor, or 5 μM SB 203580, a p38 MAP kinase inhibitor. Another group of hearts was preperfused with 20 μM anisomycin, a stimulator for both JNK and p38 MAP kinases. I/R increased the protein levels of JNK1, c-Jun, and p38 MAP kinase. PC also enhanced the induction of these kinases, but subsequent I/R-mediated increase was blocked by PC. Curcumin blocked I/R- and PC-mediated increase in JNK1 and c-Jun protein levels, whereas it had no effects on p38 MAP kinase. SB 203580, on the other hand, was equally effective in reducing the p38 MAP kinase activation but exerted no effects on JNK1 and c-Jun induction. I/R-mediated increased myocardial infarction was reduced by any of the following compounds: anisomycin, curcumin, and SB 203580. The cardioprotective effects of PC were abolished by either curcumin or SB 203580. The results demonstrate that PC is mediated by a signal-transduction pathway involving both JNK1 and p38 MAP kinase. Activation of SAPKs, although transient, is obligatory for PC.

HIV gp120 enhances NO production by cardiac myocytes through p38 MAP kinase-mediated NF-κB activation

2000 ◽  
Vol 279 (6) ◽  
pp. H3138-H3143 ◽  
Author(s):  
Hong Kan ◽  
Zirong Xie ◽  
Mitchell S. Finkel
Keyword(s):  
Protein Kinase ◽  
Cardiac Myocytes ◽  
Myocardial Dysfunction ◽  
Neonatal Rat ◽  
Inos Mrna ◽  
Protein Kinase Activity ◽  
No Production ◽  
Direct Effects ◽  
Hiv Gp120 ◽  
Hiv 1

Human immunodeficiency virus (HIV) infection is associated with a surprisingly high frequency of myocardial dysfunction. Potential mechanisms include direct effects of HIV, indirect effects mediated by cytokines, or a combination. We have previously reported that interleukin-1β (IL-1β) (500 U/ml) alone induced nitric oxide (NO) production by neonatal rat cardiac myocytes (CM). Effects of the HIV-1 envelope, glycoprotein120 (gp120), on inducible NO synthase (iNOS) in CM have not been previously reported. Unlike IL-1β, recombinant HIV-gp120 (1 μg/ml) alone failed to enhance NO production in CM (0.5 ± 0.4 vs. 0.4 ± 0.5 μmol/1.25 × 105 cells/48 h, gp120 vs. control, respectively; n = 12, P = not significant). However, the addition of gp120 to IL-1β significantly enhanced iNOS mRNA expression (70 ± 1.5 vs. 26 ± 2.4 optical units, IL-1β + gp120 vs. IL-1β, respectively; n = 3), iNOS protein synthesis (42 ± 1.4 vs. 18 ± 0.8 optical units, IL-1β + gp120 vs. IL-1β, respectively; n = 3), and NO production (NO2 −) (6.6 ± 0.6 vs. 4.1 ± 0.8 μmol/1.25 × 105 cells/48 h, IL-1β + gp120 vs. IL-1β, respectively; n = 12, P ≤ 0.5). HIV-gp120 enhancement of IL-1β-induced NO2 −production was blocked by 10 μM of SB-203580 (SB), a selective p38 protein kinase inhibitor (3.6 ± 0.2 vs. 6.6 ± 0.6 μmol/1.25 × 105 cells/48 h, IL-1β + gp120 + SB vs. IL-1β + gp120, respectively; n = 12, P ≤ 0.5). HIV-gp120-enhanced p38 protein kinase activity was associated with an increase in IL-1β-stimulated NF-κB activity (184 ± 12.7 vs. 92 ± 10.7 optical units, IL-1β + gp120 vs. IL-1β, respectively; n = 3). None of these effects was seen with another recombinant HIV-1 protein, Tat. Thus HIV-gp120 enhancement of IL-1β-induced NO production is associated with p38-mediated activation of NF-κB. Direct effects of HIV-gp120 on CM may provide a previously unrecognized mechanism contributing to HIV cardiomyopathy.

Thioredoxin Negatively Regulates p38 MAP Kinase Activation and IL-6 Production by Tumor Necrosis Factor-α

1999 ◽  
Vol 258 (2) ◽  
pp. 443-447 ◽  
Author(s):  
Shu Hashimoto ◽  
Ken Matsumoto ◽  
Yasuhiro Gon ◽  
Sachiko Furuichi ◽  
Shuichiro Maruoka ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Map Kinase ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
P38 Map Kinase ◽  
Kinase Activation ◽  
Factor Α ◽  
Necrosis Factor

Enhanced tolerance to ischaemia of thyroxine treated rat heart is associated with attenuated P38 map kinase activation

2001 ◽  
Vol 33 (6) ◽  
pp. A89
Author(s):  
Costas Pantos ◽  
Vassilliki Malliopoulou ◽  
Evangelia Karamanoli ◽  
Stelios Tzeis ◽  
Iordanis S. Mourouzis ◽  
...  
Keyword(s):  
Map Kinase ◽  
Rat Heart ◽  
P38 Map Kinase ◽  
Kinase Activation

Specific Regulation of Cytokine-Dependent p38 MAP Kinase Activation by p62/SQSTM1

2007 ◽  
Vol 143 (6) ◽  
pp. 765-772 ◽  
Author(s):  
K. Kawai ◽  
A. Saito ◽  
T. Sudo ◽  
H. Osada
Keyword(s):  
Map Kinase ◽  
P38 Map Kinase ◽  
Kinase Activation ◽  
Specific Regulation

Gαi-biased apelin analog protects against isoproterenol-induced myocardial dysfunction in rats

2021 ◽  
Vol 320 (4) ◽  
pp. H1646-H1656
Author(s):  
David Coquerel ◽  
Eugénie Delile ◽  
Lauralyne Dumont ◽  
Frédéric Chagnon ◽  
Alexandre Murza ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Left Ventricular Hypertrophy ◽  
Ventricular Hypertrophy ◽  
Myocardial Dysfunction ◽  
Negative Inotropic Effect ◽  
Left Ventricular ◽  
Inotropic Effect ◽  
Camp Production ◽  
Data Point

By using more potent Gαi-biased APJ agonists that strongly inhibit cAMP production, these data point to the negative inotropic effect of APJ-mediated Gαi signaling in the heart and highlight the potential protective impact of APJ-dependent Gαi signaling in cardiovascular diseases associated with left ventricular hypertrophy.

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