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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 opioid receptors signaling in remote electro-stimulation (RES)-induced myocardial GSK3 and PKCε expression.A non-selective opioid receptor antagonist, naloxone (1 mg/kg) (A, B, n = 4–5), and three specific opioid receptor subtypes antagonists targeting the kappa opioid receptors (KORs), delta opioid receptors (DOR)s and mu opioid receptor (MOR) antagonists (C, D, n = 4–5), were used to pretreat the animals for 15 min before RES preconditioning. Next, after RES treatment for 30 min, the heart proteins were analyzed by Western blotting. Optic density (OD) ratio = phosphorylated form divided by the total form. Only the band of GSK3-β was quantified. *, p<0.05, vs. sham RES; #, p<0.05, vs. RES-30 or RES. KOR, kappa opioid receptor; DOR, delta opioid receptor; MOR, mu opioid receptor; KOR left, KOR activity remained; DOR left, DOR activity remained; MOR left, MOR activity remained.
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pone.0138108.g003: The role of opioid receptors signaling in remote electro-stimulation (RES)-induced myocardial GSK3 and PKCε expression.A non-selective opioid receptor antagonist, naloxone (1 mg/kg) (A, B, n = 4–5), and three specific opioid receptor subtypes antagonists targeting the kappa opioid receptors (KORs), delta opioid receptors (DOR)s and mu opioid receptor (MOR) antagonists (C, D, n = 4–5), were used to pretreat the animals for 15 min before RES preconditioning. Next, after RES treatment for 30 min, the heart proteins were analyzed by Western blotting. Optic density (OD) ratio = phosphorylated form divided by the total form. Only the band of GSK3-β was quantified. *, p<0.05, vs. sham RES; #, p<0.05, vs. RES-30 or RES. KOR, kappa opioid receptor; DOR, delta opioid receptor; MOR, mu opioid receptor; KOR left, KOR activity remained; DOR left, DOR activity remained; MOR left, MOR activity remained.

Mentions: To investigate the role of opioid receptors signaling in RES-induced myocardial GSK3 and PKCε activation, a non-selective opioid receptor antagonist, naloxone (1 mg/kg), was used to pretreat the animals for 15 min before RES on bil. median nerves. The results showed that RES-induced GSK3 and PKCε phosphorylation was blocked by naloxone treatment (Fig 3A and 3B, n = 4–5), which suggests the opioid receptor signaling also plays a role in GSK3 and PKCε phosphorylation.


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 opioid receptors signaling in remote electro-stimulation (RES)-induced myocardial GSK3 and PKCε expression.A non-selective opioid receptor antagonist, naloxone (1 mg/kg) (A, B, n = 4–5), and three specific opioid receptor subtypes antagonists targeting the kappa opioid receptors (KORs), delta opioid receptors (DOR)s and mu opioid receptor (MOR) antagonists (C, D, n = 4–5), were used to pretreat the animals for 15 min before RES preconditioning. Next, after RES treatment for 30 min, the heart proteins were analyzed by Western blotting. Optic density (OD) ratio = phosphorylated form divided by the total form. Only the band of GSK3-β was quantified. *, p<0.05, vs. sham RES; #, p<0.05, vs. RES-30 or RES. KOR, kappa opioid receptor; DOR, delta opioid receptor; MOR, mu opioid receptor; KOR left, KOR activity remained; DOR left, DOR activity remained; MOR left, MOR activity remained.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0138108.g003: The role of opioid receptors signaling in remote electro-stimulation (RES)-induced myocardial GSK3 and PKCε expression.A non-selective opioid receptor antagonist, naloxone (1 mg/kg) (A, B, n = 4–5), and three specific opioid receptor subtypes antagonists targeting the kappa opioid receptors (KORs), delta opioid receptors (DOR)s and mu opioid receptor (MOR) antagonists (C, D, n = 4–5), were used to pretreat the animals for 15 min before RES preconditioning. Next, after RES treatment for 30 min, the heart proteins were analyzed by Western blotting. Optic density (OD) ratio = phosphorylated form divided by the total form. Only the band of GSK3-β was quantified. *, p<0.05, vs. sham RES; #, p<0.05, vs. RES-30 or RES. KOR, kappa opioid receptor; DOR, delta opioid receptor; MOR, mu opioid receptor; KOR left, KOR activity remained; DOR left, DOR activity remained; MOR left, MOR activity remained.
Mentions: To investigate the role of opioid receptors signaling in RES-induced myocardial GSK3 and PKCε activation, a non-selective opioid receptor antagonist, naloxone (1 mg/kg), was used to pretreat the animals for 15 min before RES on bil. median nerves. The results showed that RES-induced GSK3 and PKCε phosphorylation was blocked by naloxone treatment (Fig 3A and 3B, n = 4–5), which suggests the opioid receptor signaling also plays a role in GSK3 and PKCε phosphorylation.

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