| First Author | Lips DJ | Year | 2004 |
| Journal | Circulation | Volume | 109 |
| Issue | 16 | Pages | 1938-41 |
| PubMed ID | 15096454 | Mgi Jnum | J:127872 |
| Mgi Id | MGI:3765168 | Doi | 10.1161/01.CIR.0000127126.73759.23 |
| Citation | Lips DJ, et al. (2004) MEK1-ERK2 signaling pathway protects myocardium from ischemic injury in vivo. Circulation 109(16):1938-41 |
| abstractText | BACKGROUND: Myocardial infarction causes a rapid and largely irreversible loss of cardiac myocytes that can lead to sudden death, ventricular dilation, and heart failure. Members of the mitogen-activated protein kinase (MAPK) signaling cascade have been implicated as important effectors of cardiac myocyte cell death in response to diverse stimuli, including ischemia-reperfusion injury. Specifically, activation of the extracellular signal-regulated kinases 1/2 (ERK1/2) has been associated with cardioprotection, likely through antagonism of apoptotic regulatory pathways. METHODS AND RESULTS: To establish a causal relationship between ERK1/2 signaling and cardioprotection, we analyzed Erk1 nullizygous gene-targeted mice, Erk2 heterozygous gene-targeted mice, and transgenic mice with activated MEK1-ERK1/2 signaling in the heart. Although MEK1 transgenic mice were largely resistant to ischemia-reperfusion injury, Erk2+/- gene-targeted mice showed enhanced infarction areas, DNA laddering, and terminal deoxynucleotidyl transferase-mediated dUTP biotin nick-end labeling (TUNEL) compared with littermate controls. In contrast, enhanced MEK1-ERK1/2 signaling protected hearts from DNA laddering, TUNEL, and preserved hemodynamic function assessed by pressure-volume loop recordings after ischemia-reperfusion injury. CONCLUSIONS: These data are the first to demonstrate that ERK2 signaling is required to protect the myocardium from ischemia-reperfusion injury in vivo. |
