期刊
REGULATORY PEPTIDES
卷 174, 期 1-3, 页码 90-97出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.regpep.2011.12.005
关键词
CRF; CRFR2; Ischemia; PKA; PKC; Cardioprotection; Apoptosis
资金
- University of Bergen
- Heart Foundation
- L Meltzer Foundation
- Norwegian Heart Foundation
Corticotrophin-releasing factor receptor 213 (CRFR213) is expressed in the myocardium. In the present study we explore whether acute treatment with the neuropeptide corticotrophin-releasing factor (CRF) could induce cytoprotection against a lethal ischemic insult in the heart (isolated murine neonatal cardiac myocytes and the isolated Langendorff perfused rat heart) by activating CRFR2. In vitro, CRF offered cytoprotection when added prior to lethal simulated ischemic stress by reducing apoptotic and necrotic cell death. Ex vivo, CRF significantly reduced infarct size from 52.1 +/- 3.1% in control hearts to 35.3 +/- 3.1% (P<0.001) when administered prior to a lethal ischemic insult The CRF peptide did not confer cytoprotection when administered at the point of hypoxic reoxygenation or ischemic reperfusion. The acute effects of CRF treatment are mediated by CRF receptor type 2 (CRFR2) since the cardioprotection ex vivo was inhibited by the CRFR2 antagonist astressin-2B. Inhibition of the mitogen activated protein kinase-ERK1/2 by PD98059 failed to inhibit the effect of CRF. However, both protein kinase A and protein kinase C inhibitors abrogated CRF-mediated protection both ex vivo and in vitro. These data suggest that the CRF peptide reduces both apoptotic and necrotic cell death in cardiac myocytes subjected to lethal ischemic induced stress through activation of PKA and PKC dependent signaling pathways downstream of CRFR2. (C) 2011 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据