Activation of JNK in the Remote Myocardium after Large Myocardial Infarction in Rats

Li, Wei Gen; Zaheer, Asgar; Coppey, Lawrence J.; Oskarsson, Helgi

doi:10.1006/bbrc.1998.8662

Cited by 46 publications

(21 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…JNK, which is a major player in the process of cardiac hypertrophy and myocardial extracellular matrix remodeling, is activated under a variety of pathological conditions, including hypertension, ischemia/reperfusion injury, and myocardial infarction (Li et al, 1998;Pellieux et al, 2000). Upstream (Map3k6 and Map3k8) and downstream (ATF-2) signaling events detected in our study (Table 2; Fig.…”

Section: Discussionmentioning

confidence: 60%

Doxycycline Attenuates Isoproterenol- and Transverse Aortic Banding-Induced Cardiac Hypertrophy in Mice

Errami

Galindo

Tassa

et al. 2007

J Pharmacol Exp Ther

View full text Add to dashboard Cite

The United States Food and Drug Administration-approved antibiotic doxycycline (DOX) inhibits matrix metalloproteases, which contribute to the development of cardiac hypertrophy (CH). We hypothesized that DOX might serve as a treatment for CH. The efficacy of DOX was tested in two mouse models of CH: induced by the ␤-adrenergic agonist isoproterenol (ISO) and induced by transverse aortic banding. DOX significantly attenuated CH in these models, causing a profound reduction of the hypertrophic phenotype and a lower heart/body weight ratio (p Ͻ 0.05, n Ն 6). As expected, ISO increased matrix metalloprotease (MMP) 2 and 9 activities, and administration of DOX reversed this effect. Transcriptional profiles of normal, ISO-, and ISO ϩ DOX-treated mice were examined using microarrays, and the results were confirmed by real-time reverse transcriptase-polymerase chain reaction. Genes (206) were differentially expressed between normal and ISO mice that were reversibly altered between ISO-and ISO ϩ DOX-treated mice, indicating their potential role in CH development and DOX-induced improvement. These genes included those involved in the regulation of cell proliferation and fate, stress, and immune responses, cytoskeleton and extracellular matrix organization, and cardiac-specific signal transduction. The overall gene expression profile suggested that MMP2/9 inactivation was not the only mechanism whereby DOX exerts its beneficial effects. Western blot analysis identified potential signaling events associated with CH, including up-regulation of endothelial differentiation sphingolipid G-protein-coupled receptor 1 receptor and activation of extracellular signal-regulated kinase, p38, and the transcription factor activating transcription factor-2, which were reduced after administration of DOX. These results suggest that DOX might be evaluated as a potential CH therapeutic and also provide potential signaling mechanisms to investigate in the context of CH phenotype development and regression.

show abstract

Section: Discussionmentioning

confidence: 60%

Doxycycline Attenuates Isoproterenol- and Transverse Aortic Banding-Induced Cardiac Hypertrophy in Mice

Errami

Galindo

Tassa

et al. 2007

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…In addition to their role in regulation myocyte hypertrophy, there is increasing evidence for a role for activated stress-response kinases in the regulation of myocyte survival. Overexpression or increased activation of JNKs and p38-MAPKs promotes apoptotic myocyte death, 27,28 whereas inhibition of p38-MAPKs decreases apoptosis after myocardial ischemia and reperfusion, 29 suggesting that the ERKs and the SAPKs have antagonistic roles in mediating apoptotic cell death. 30 Thus, the characterization of myocyte survival pathways indicates that activation of these pathways may drive the onset of myocyte and subsequent muscle remodeling in response to biomechanical stress.…”

Section: Fischer Et Al Cardiac Sapks After Aortic Bandingmentioning

confidence: 99%

Activation of Cardiac c-Jun NH ₂ -Terminal Kinases and p38-Mitogen–Activated Protein Kinases With Abrupt Changes in Hemodynamic Load

Fischer¹,

Ludwig²,

Flory³

et al. 2001

Hypertension

View full text Add to dashboard Cite

Abstract-The role of mitogen-activated protein kinase (MAPK) pathways as signal transduction intermediates of hemodynamic stress leading to cardiac hypertrophy in the adult heart is not fully established. In a rat model of pressure-overload hypertrophy, we examined whether activation of MAPK pathways, namely, the extracellular signal-regulated protein kinase (ERK), c-Jun NH 2 -terminal kinase (JNK), and the p38-MAPK pathways, occurs during rapid changes in hemodynamic load in vivo. A slight activation of ERK2 and marked increases in JNK1 and p38-MAPK activities were observed 30 minutes after aortic banding. The increase in p38-MAPK activity was accompanied by an increase in the phosphorylation of the p38 substrate MAPK-activated protein kinases 2 and 3. Activation of these kinases was coincident with an increase in phosphorylation of c-Jun and activating transcription factor-2 (ATF-2) and enhanced DNA binding of activator protein-1 factors. Thus, hemodynamic stress of the adult rat heart in vivo results in rapid activation of several parallel MAPK kinase cascades, particularly stress-activated MAPK and p38-MAPK and their target transcription factors c-Jun and ATF-2. (Hypertension. 2001;37:1222-1228.)

show abstract

“…Inhibition of ERK activity increases cardiac myocyte death secondary to oxidative damage [41] and the ERKs are implicated in the phosphorylation/inactivation of Bad [37] . The JNKs appear to be pro-apoptotic and experiments suggest JNK signalling is involved in apoptosis secondary to oxidative stress [63] , TNF- [64] and in animal models of AMI [65] . Recently, a novel kinase that acts upstream in the JNK/p38-MAPK signalling pathways has been identified.…”

Section: Non Death-receptor Mediated Apoptosismentioning

confidence: 99%

Cardiac myocyte apoptosis

Cook

Poole‐Wilson

1999

European Heart Journal

View full text Add to dashboard Cite

Activation of JNK in the Remote Myocardium after Large Myocardial Infarction in Rats

Cited by 46 publications

References 28 publications

Doxycycline Attenuates Isoproterenol- and Transverse Aortic Banding-Induced Cardiac Hypertrophy in Mice

Doxycycline Attenuates Isoproterenol- and Transverse Aortic Banding-Induced Cardiac Hypertrophy in Mice

Activation of Cardiac c-Jun NH ₂ -Terminal Kinases and p38-Mitogen–Activated Protein Kinases With Abrupt Changes in Hemodynamic Load

Cardiac myocyte apoptosis

Contact Info

Product

Resources

About

Activation of JNK in the Remote Myocardium after Large Myocardial Infarction in Rats

Cited by 46 publications

References 28 publications

Doxycycline Attenuates Isoproterenol- and Transverse Aortic Banding-Induced Cardiac Hypertrophy in Mice

Doxycycline Attenuates Isoproterenol- and Transverse Aortic Banding-Induced Cardiac Hypertrophy in Mice

Activation of Cardiac c-Jun NH 2 -Terminal Kinases and p38-Mitogen–Activated Protein Kinases With Abrupt Changes in Hemodynamic Load

Cardiac myocyte apoptosis

Contact Info

Product

Resources

About

Activation of Cardiac c-Jun NH ₂ -Terminal Kinases and p38-Mitogen–Activated Protein Kinases With Abrupt Changes in Hemodynamic Load