Paediatrics Publications
Document Type
Article
Publication Date
3-1-2018
Journal
International Journal of Molecular Medicine
Volume
41
Issue
3
First Page
1724
Last Page
1730
URL with Digital Object Identifier
10.3892/ijmm.2017.3338
Abstract
Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel and a molecular integrator of noxious stimuli. TRPV1 activation confers cardiac protection against ischemia/reperfusion (I/R) injury. The present study aimed to investigate whether the cardioprotective effects of TRPV1 were associated with the inhibition of apoptosis via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) signaling pathways. Briefly, the hearts of TRPV1 knockout (TRPV1-/-) or wild-type (WT) mice were isolated and subjected to 30 min of ischemia followed by 60 min of reperfusion in a Langendorff apparatus in the presence or absence of the PI3K inhibitor, LY294002. At the end of reperfusion, infarct size was measured using 2, 3, 5-triphenyltetrazolium chloride staining and myocardial apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. The expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and phosphorylated Akt and ERK1/2 were determined by western blot analysis. There was a significant increase in the extent of infarction and the percentage of TUNEL-positive cells, and a decrease in the Bcl-2/Bax ratio, and Akt and ERK1/2 phosphorylation in TRPV1-/- hearts. In addition, treatment with LY294002 increased infarct size and the percentage of TUNEL-positive cells, and reduced Bcl-2/Bax expression and Akt phosphorylation in WT hearts, but not in TRPV1-/- hearts, following I/R. Taken together, these data suggested that TRPV1 serves a protective role against myocardial apoptosis during I/R via the PI3K/Akt signaling pathway. In conclusion, activating TRPV1 may be considered a potential approach to protect the heart against I/R injury.