Activation of transient receptor potential vanilloid 1 protects the heart against apoptosis in ischemia/reperfusion injury through upregulating the PI3K/Akt signaling pathway

Jiang,Xiao‑Xue; Liu,Guan‑Yu; Lei,Han; Li,Zuo‑Ling; Feng,Qing‑Ping; Huang,Wei

doi:10.3892/ijmm.2017.3338

Activation of transient receptor potential vanilloid 1 protects the heart against apoptosis in ischemia/reperfusion injury through upregulating the PI3K/Akt signaling pathway

Authors:
- Xiao‑Xue Jiang
- Guan‑Yu Liu
- Han Lei
- Zuo‑Ling Li
- Qing‑Ping Feng
- Wei Huang
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Affiliations: Cardiovascular Laboratory, Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Department of Physiology and Pharmacology, University of Western Ontario, London, ON N6A‑5C1, Canada
Published online on: December 21, 2017 https://doi.org/10.3892/ijmm.2017.3338
Pages: 1724-1730

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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.

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