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Role of Opioid Receptors Signaling in Remote Electrostimulation--Induced Protection against Ischemia/Reperfusion Injury in Rat Hearts.

Tsai HJ, Huang SS, Tsou MT, Wang HT, Chiu JH - PLoS ONE (2015)

Bottom Line: Our results showed that Akt, GSK3 and PKCε expression levels were significantly increased in the RES group compared to the sham group, which were blocked by pretreatment with specific antagonists targeting KOR and DOR, but not MOR subtype.Using the I/R model, the duration of arrhythmia and infarct size were both significantly attenuated in RES group.The mortality rates of the sham RES group, the RES group, RES group + KOR antagonist, RES group + DOR/MOR antagonists (KOR left), RES group + DOR antagonist, and RES group + KOR/MOR antagonists (DOR left) were 50%, 20%, 67%, 13%, 50% and 55%, respectively.

View Article: PubMed Central - PubMed

Affiliation: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.

ABSTRACT

Aims: Our previous studies demonstrated that remote electro-stimulation (RES) increased myocardial GSK3 phosphorylation and attenuated ischemia/ reperfusion (I/R) injury in rat hearts. However, the role of various opioid receptors (OR) subtypes in preconditioned RES-induced myocardial protection remains unknown. We investigated the role of OR subtype signaling in RES-induced cardioprotection against I/R injury of the rat heart.

Methods & results: Male Spraque-Dawley rats were used. RES was performed on median nerves area with/without pretreatment with various receptors antagonists such as opioid receptor (OR) subtype receptors (KOR, DOR, and MOR). The expressions of Akt, GSK3, and PKCε expression were analyzed by Western blotting. When RES was preconditioned before the I/R model, the rat's hemodynamic index, infarction size, mortality and serum CK-MB were evaluated. Our results showed that Akt, GSK3 and PKCε expression levels were significantly increased in the RES group compared to the sham group, which were blocked by pretreatment with specific antagonists targeting KOR and DOR, but not MOR subtype. Using the I/R model, the duration of arrhythmia and infarct size were both significantly attenuated in RES group. The mortality rates of the sham RES group, the RES group, RES group + KOR antagonist, RES group + DOR/MOR antagonists (KOR left), RES group + DOR antagonist, and RES group + KOR/MOR antagonists (DOR left) were 50%, 20%, 67%, 13%, 50% and 55%, respectively.

Conclusion: The mechanism of RES-induced myocardial protection against I/R injury seems to involve multiple target pathways such as Akt, KOR and/or DOR signaling.

No MeSH data available.


Related in: MedlinePlus

The role of α-adrenergic receptor, β-adrenergic receptor and muscarinic receptor signaling in remote electro-stimulation (RES)-induced Akt phosphorylation.Rat hearts were harvested at the designated time points of 0 min, 30min and 60 min after RES preconditioning and then analyzed by Western blotting (A) followed by quantification (B). For mechanistic analysis, rat hearts pretreated with phentolamine, an α-adrenergic receptor antagonist, with propanolol, a β-adrenergic receptor antagonist, and with atropine, a muscarinic receptor antagonist, were harvested at 30 min after RES stimulation and the proteins were analyzed with Western blotting (C), followed by quantification (D). Optic density (OD) ratio = phosphorylated form divided by the total form. Only the band of GSK3-β was quantified. *, p<0.05, vs. anesthesia alone; #, p<0.05, vs. sham RES; n = 4 in each group.
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pone.0138108.g002: The role of α-adrenergic receptor, β-adrenergic receptor and muscarinic receptor signaling in remote electro-stimulation (RES)-induced Akt phosphorylation.Rat hearts were harvested at the designated time points of 0 min, 30min and 60 min after RES preconditioning and then analyzed by Western blotting (A) followed by quantification (B). For mechanistic analysis, rat hearts pretreated with phentolamine, an α-adrenergic receptor antagonist, with propanolol, a β-adrenergic receptor antagonist, and with atropine, a muscarinic receptor antagonist, were harvested at 30 min after RES stimulation and the proteins were analyzed with Western blotting (C), followed by quantification (D). Optic density (OD) ratio = phosphorylated form divided by the total form. Only the band of GSK3-β was quantified. *, p<0.05, vs. anesthesia alone; #, p<0.05, vs. sham RES; n = 4 in each group.

Mentions: To determine the effect of RES on Akt and GSK3 expression in rats, hearts were harvested at the specific time points (0 min, 30 min and 60 min) after RES on the area of the bilateral median nerve and tissue samples from these hearts were then analyzed by Western blotting. The results showed that RES-induced activation of the protein kinase B/Akt resulted a peak in activity at 30 min after RES, followed by a decline at 60 min after stimulation (Fig 2A and 2B, n = 4); this activation was blocked by pretreatment with phentolamine (an α- adrenergic receptor antagonist) and by propanolol (a β-adrenergic receptor antagonist), but not by atropine (a muscarinic receptor antagonist). These findings suggest that both adrenergic receptors play a role in RES-induced Akt activation (Fig 2C and 2D, n = 4).


Role of Opioid Receptors Signaling in Remote Electrostimulation--Induced Protection against Ischemia/Reperfusion Injury in Rat Hearts.

Tsai HJ, Huang SS, Tsou MT, Wang HT, Chiu JH - PLoS ONE (2015)

The role of α-adrenergic receptor, β-adrenergic receptor and muscarinic receptor signaling in remote electro-stimulation (RES)-induced Akt phosphorylation.Rat hearts were harvested at the designated time points of 0 min, 30min and 60 min after RES preconditioning and then analyzed by Western blotting (A) followed by quantification (B). For mechanistic analysis, rat hearts pretreated with phentolamine, an α-adrenergic receptor antagonist, with propanolol, a β-adrenergic receptor antagonist, and with atropine, a muscarinic receptor antagonist, were harvested at 30 min after RES stimulation and the proteins were analyzed with Western blotting (C), followed by quantification (D). Optic density (OD) ratio = phosphorylated form divided by the total form. Only the band of GSK3-β was quantified. *, p<0.05, vs. anesthesia alone; #, p<0.05, vs. sham RES; n = 4 in each group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4592126&req=5

pone.0138108.g002: The role of α-adrenergic receptor, β-adrenergic receptor and muscarinic receptor signaling in remote electro-stimulation (RES)-induced Akt phosphorylation.Rat hearts were harvested at the designated time points of 0 min, 30min and 60 min after RES preconditioning and then analyzed by Western blotting (A) followed by quantification (B). For mechanistic analysis, rat hearts pretreated with phentolamine, an α-adrenergic receptor antagonist, with propanolol, a β-adrenergic receptor antagonist, and with atropine, a muscarinic receptor antagonist, were harvested at 30 min after RES stimulation and the proteins were analyzed with Western blotting (C), followed by quantification (D). Optic density (OD) ratio = phosphorylated form divided by the total form. Only the band of GSK3-β was quantified. *, p<0.05, vs. anesthesia alone; #, p<0.05, vs. sham RES; n = 4 in each group.
Mentions: To determine the effect of RES on Akt and GSK3 expression in rats, hearts were harvested at the specific time points (0 min, 30 min and 60 min) after RES on the area of the bilateral median nerve and tissue samples from these hearts were then analyzed by Western blotting. The results showed that RES-induced activation of the protein kinase B/Akt resulted a peak in activity at 30 min after RES, followed by a decline at 60 min after stimulation (Fig 2A and 2B, n = 4); this activation was blocked by pretreatment with phentolamine (an α- adrenergic receptor antagonist) and by propanolol (a β-adrenergic receptor antagonist), but not by atropine (a muscarinic receptor antagonist). These findings suggest that both adrenergic receptors play a role in RES-induced Akt activation (Fig 2C and 2D, n = 4).

Bottom Line: Our results showed that Akt, GSK3 and PKCε expression levels were significantly increased in the RES group compared to the sham group, which were blocked by pretreatment with specific antagonists targeting KOR and DOR, but not MOR subtype.Using the I/R model, the duration of arrhythmia and infarct size were both significantly attenuated in RES group.The mortality rates of the sham RES group, the RES group, RES group + KOR antagonist, RES group + DOR/MOR antagonists (KOR left), RES group + DOR antagonist, and RES group + KOR/MOR antagonists (DOR left) were 50%, 20%, 67%, 13%, 50% and 55%, respectively.

View Article: PubMed Central - PubMed

Affiliation: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.

ABSTRACT

Aims: Our previous studies demonstrated that remote electro-stimulation (RES) increased myocardial GSK3 phosphorylation and attenuated ischemia/ reperfusion (I/R) injury in rat hearts. However, the role of various opioid receptors (OR) subtypes in preconditioned RES-induced myocardial protection remains unknown. We investigated the role of OR subtype signaling in RES-induced cardioprotection against I/R injury of the rat heart.

Methods & results: Male Spraque-Dawley rats were used. RES was performed on median nerves area with/without pretreatment with various receptors antagonists such as opioid receptor (OR) subtype receptors (KOR, DOR, and MOR). The expressions of Akt, GSK3, and PKCε expression were analyzed by Western blotting. When RES was preconditioned before the I/R model, the rat's hemodynamic index, infarction size, mortality and serum CK-MB were evaluated. Our results showed that Akt, GSK3 and PKCε expression levels were significantly increased in the RES group compared to the sham group, which were blocked by pretreatment with specific antagonists targeting KOR and DOR, but not MOR subtype. Using the I/R model, the duration of arrhythmia and infarct size were both significantly attenuated in RES group. The mortality rates of the sham RES group, the RES group, RES group + KOR antagonist, RES group + DOR/MOR antagonists (KOR left), RES group + DOR antagonist, and RES group + KOR/MOR antagonists (DOR left) were 50%, 20%, 67%, 13%, 50% and 55%, respectively.

Conclusion: The mechanism of RES-induced myocardial protection against I/R injury seems to involve multiple target pathways such as Akt, KOR and/or DOR signaling.

No MeSH data available.


Related in: MedlinePlus