Substance P induces cardioprotection in ischemia-reperfusion via activation of AKT
| Autor: | Heather M. Dehlin, Shaiban Jubair, Edward J. Manteufel, Scott P. Levick, Paul H. Goldspink, Jianping Li, Joseph S. Janicki |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty Cardiotonic Agents Physiology medicine.drug_class Substance P Myocardial Reperfusion Injury Rats Sprague-Dawley chemistry.chemical_compound Mice Integrative Cardiovascular Physiology and Pathophysiology Physiology (medical) Internal medicine Medicine Animals Myocytes Cardiac Receptor Protein kinase B Cell damage PI3K/AKT/mTOR pathway Cells Cultured Cardioprotection business.industry Receptors Neurokinin-1 medicine.disease Receptor antagonist Cell Hypoxia Rats Mice Inbred C57BL Endocrinology chemistry Coronary vasodilator Cardiology and Cardiovascular Medicine business Proto-Oncogene Proteins c-akt Signal Transduction |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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