Faculty Collaboration Database

Substance P induces cardioprotection in ischemia-reperfusion via activation of AKT. Am J Physiol Heart Circ Physiol 2015 Aug 15;309(4):H676-84

Date

06/14/2015

Pubmed ID

26071541

Pubmed Central ID

PMC4537946

DOI

10.1152/ajpheart.00200.2015

Scopus ID

2-s2.0-84939443820 (requires institutional sign-in at Scopus site)   21 Citations

Abstract

Accumulating evidence indicates that substance P is cardioprotective following ischemia-reperfusion primarily due to its potent coronary vasodilator actions. However, an anti-apoptotic effect of substance P has been observed in tenocytes following ischemia, which involved activation of the AKT pathway. This suggests the possibility that substance P also provides cardioprotection via direct actions to activate AKT in myocardial cells. The purpose of this study was to test the hypothesis that substance P attenuates ischemia-related cell death via direct effects on myocardial cells by activating cell survival pathways. Seven-week-old male Sprague-Dawley rats, anesthetized with intraperitoneal pentobarbital sodium (100 mg/kg), were used. The ability of substance P to prevent cellular damage was assessed following ischemia-reperfusion in an isolated heart preparation and in short-term hypoxia without reperfusion using a left ventricular tissue slice culture preparation. In addition, the NK-1 receptor and AKT involvement was assessed using the NK-1 receptor antagonist L732138 and the AKT inhibitor LY294002. The results indicate that substance P reduced the ischemia-related release of lactate dehydrogenase in both preparations and the degree of apoptosis and necrosis in the hypoxic left ventricular slices, indicating its ability to attenuate cell damage; and induced AKT phosphorylation, with both the AKT inhibitor and NK-1 receptor antagonist preventing the increased phosphorylation of AKT and the ability of substance P to attenuate hypoxic cellular damage. It is concluded that substance P reduces ischemia/hypoxia-induced myocardial cell death by acting directly on cardiac cells to initiate cell survival pathways via the NK-1 receptor and AKT.

Author List

Jubair S, Li J, Dehlin HM, Manteufel EJ, Goldspink PH, Levick SP, Janicki JS

MESH terms used to index this publication - Major topics in bold

Animals
Cardiotonic Agents
Cell Hypoxia
Cells, Cultured
Male
Mice
Mice, Inbred C57BL
Myocardial Reperfusion Injury
Myocytes, Cardiac
Proto-Oncogene Proteins c-akt
Rats
Rats, Sprague-Dawley
Receptors, Neurokinin-1
Signal Transduction
Substance P