Abstract
Cholecystokinin (CCK-8) has been shown to exhibit pharmacological preconditioning and cardioprotective effects. However, the molecular mechanisms involved in CCK-8-induced pharmacological preconditioning have not yet been clarified. The current study explored the molecular mechanisms involved in CCK-8-mediated pharmacological preconditioning effects on ischemic rat hearts. Pharmacological preconditioning was induced in male Wistar rats by administration of CCK-8 (20 μg/kg) 24 h before heart isolation. The PI3K inhibitor LY294002 (10 mg/kg and 20 mg/kg) and the HIF-1α inhibitor YC-1 (1 mg/kg and 2 mg/kg) were administered 30 min before the administration of CCK-8. The hearts were subjected to ischemia-reperfusion (IR) injury using a Langendorff apparatus. Myocardial injury was quantified by measuring the release of LDH-1, CK-MB and cTnT. The levels of HIF-1α and p-Akt expression and the ratio of p-GSK-3β/GSK-3β, were assessed in the heart homogenates. Pharmacological preconditioning with CCK-8 reduced IR-induced increases in the release of LDH, CK-MB and cTnT. Moreover, it restored the expression of HIF-1α and p-Akt, and the p-GSK-3β/GSK-3β ratio. However, administration of LY294002 or YC-1 with CCK-8 significantly abolished the cardioprotective effects of pharmacological preconditioning. The PI3K and HIF-1α inhibitors also abolished the effects of CCK-8 preconditioning on HIF-1α, p-Akt and p-GSK-3β/GSK-3β. Based on these findings, it may be concluded that the molecular mechanisms participating in CCK-8-induced pharmacological preconditioning involve HIF-1α, PI3K, Akt, and GSK-3β signaling pathways.
Highlights
Cholecystokinin (CCK-8) has been shown to exhibit pharmacological preconditioning and cardioprotective effects
The Phosphoinositide 3-kinase (PI3K) and Hypoxia-inducible factor 1-α (HIF-1α) inhibitors abolished the effects of CCK-8 preconditioning on HIF-1α, p-Akt and p-glycogen synthase kinase-3β (GSK-3β)/GSK-3β
It may be concluded that the molecular mechanisms participating in CCK-8-induced pharmacological preconditioning involve HIF-1α, PI3K, Akt, and GSK-3β signaling pathways
Summary
Cholecystokinin (CCK-8) has been shown to exhibit pharmacological preconditioning and cardioprotective effects. The molecular mechanisms involved in CCK-8-induced pharmacological preconditioning have not yet been clarified. Interruption of blood flow in the form of ischemia induces severe heart injury, and early restoration of blood flow is essential to salvage ischemic heart. Thrombolysis or angioplasty is typically employed in clinical settings to restore the blood supply to ischemic heart.[1] reperfusion of the ischemic heart itself produces myocardial injury, which is referred to as “reperfusion injury”.2. The term “ischemia-reperfusion-induced myocardial injury” is used to denote myocardial injury that occurs during ischemia and reperfusion (IR). There are no well-established pharmacological agents to prevent IR-induced heart injury. There is a need to find new interventions/pharmacological agents that can limit or prevent IR-induced myocardial injury
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Advances in clinical and experimental medicine : official organ Wroclaw Medical University
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
