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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

Molecular evidence of kappa opioid receptor (KOR) in rat heart.After rat hearts were harvested from the animals, total RNA was isolated and tissue specimen prepared for real-time PCR (A) and immunofluorecent staining (B) as described in Methods. The real-time PCR was analyzed using glyceraldehyde-3-phosphate dehydrogenase (G3PDH) as internal control and normalized using mu opioid receptor as relative baseline level. KOR, kappa opioid receptor; DOR, delta opioid receptor; MOR, mu opioid receptor. Yellow arrows indicate the localization of KOR in cardiomyotes while white arrow heads indicate the margin of a vessel. The results were repeated in three independent experiments, only represented figure was shown.
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pone.0138108.g007: Molecular evidence of kappa opioid receptor (KOR) in rat heart.After rat hearts were harvested from the animals, total RNA was isolated and tissue specimen prepared for real-time PCR (A) and immunofluorecent staining (B) as described in Methods. The real-time PCR was analyzed using glyceraldehyde-3-phosphate dehydrogenase (G3PDH) as internal control and normalized using mu opioid receptor as relative baseline level. KOR, kappa opioid receptor; DOR, delta opioid receptor; MOR, mu opioid receptor. Yellow arrows indicate the localization of KOR in cardiomyotes while white arrow heads indicate the margin of a vessel. The results were repeated in three independent experiments, only represented figure was shown.

Mentions: To validate the presence of KOR in rat heart, real-time PCR and immunostaining were performed. The results showed that the level of mRNA transcript of ORs in rat heart (Fig 7A), and Fig 7B demonstrated the localization of KOR in rat myocardiocytes, indicating KOR was de novo synthesized.


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)

Molecular evidence of kappa opioid receptor (KOR) in rat heart.After rat hearts were harvested from the animals, total RNA was isolated and tissue specimen prepared for real-time PCR (A) and immunofluorecent staining (B) as described in Methods. The real-time PCR was analyzed using glyceraldehyde-3-phosphate dehydrogenase (G3PDH) as internal control and normalized using mu opioid receptor as relative baseline level. KOR, kappa opioid receptor; DOR, delta opioid receptor; MOR, mu opioid receptor. Yellow arrows indicate the localization of KOR in cardiomyotes while white arrow heads indicate the margin of a vessel. The results were repeated in three independent experiments, only represented figure was shown.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0138108.g007: Molecular evidence of kappa opioid receptor (KOR) in rat heart.After rat hearts were harvested from the animals, total RNA was isolated and tissue specimen prepared for real-time PCR (A) and immunofluorecent staining (B) as described in Methods. The real-time PCR was analyzed using glyceraldehyde-3-phosphate dehydrogenase (G3PDH) as internal control and normalized using mu opioid receptor as relative baseline level. KOR, kappa opioid receptor; DOR, delta opioid receptor; MOR, mu opioid receptor. Yellow arrows indicate the localization of KOR in cardiomyotes while white arrow heads indicate the margin of a vessel. The results were repeated in three independent experiments, only represented figure was shown.
Mentions: To validate the presence of KOR in rat heart, real-time PCR and immunostaining were performed. The results showed that the level of mRNA transcript of ORs in rat heart (Fig 7A), and Fig 7B demonstrated the localization of KOR in rat myocardiocytes, indicating KOR was de novo synthesized.

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