Alpha7 nicotinic acetylcholine receptor activation protects against myocardial reperfusion injury through modulation of autophagy

Journal Article · Fri Jun 15 04:00:00 EDT 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.04.077· OSTI ID:23125196

Hou, Zuoxu ^[1]; Zhou, Yaguang ^[2]; Yang, Hongyan ^[1]; Liu, Yan ^[3]; Mao, Xuechao; Qin, Xinghua ^[1]; Li, Xiaoliang ^[4]; Zhang, Xing ^[1]; Hu, Yuanyuan ^[5]

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1. Department of Aerospace Medicine, Fourth Military Medical University, Xi'an 710032 (China)
2. Department of Physiology, Fourth Military Medical University, Xi'an 710032 (China)
3. Department of Prosthodontics, School of Stomatology, Fourth Military Medical University, Xi'an 710032 (China)
4. Department of Emergency Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an 710032 (China)
5. College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710032 (China)

Alpha7 nicotinic acetylcholine receptor (α7nAChR) activation alleviates myocardial ischemia/reperfusion (MI/R) injury. However, the underlying mechanisms remain unclear. Here, we investigated the role of autophagy in α7nAChR-mediated cardioprotection and the molecular mechanisms involved. Activating α7nAChR with PNU-282987 at the initiation of reperfusion reduced myocardial infarct size in MI/R rats. PNU-282987 treatment also significantly inhibited MI/R-induced myocardial autophagy dysfunction as evidenced by the reduction of LC3-II/LC3-I ratio, Beclin-1 and p62 abundance. In addition, PNU-282987 treatment reduced hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury in vitro, accompanied with the inhibition of Beclin-1-associated autophagy and the restoration of autophagic flux. Interestingly, inhibiting autophagic flux attenuated α7nAChR-afforded improvement of mitochondrial function as well as inhibition of apoptosis in vitro. Mechanistically, co-administration of PNU-282987 with LY294002 (a PI3K inhibitor), AG490 (a JAK2 inhibitor) or Bcl-2 siRNA, but not compound C (an AMPK inhibitor), reduced Bcl-2 level and prevented the modulation of autophagy afforded by PNU-282987 in H/R cardiomyocytes. Collectively, these findings suggest that α7nAChR activation inhibits Beclin-1-associated autophagy dysfunction via the JAK2/Bcl-2 and PI3K/Bcl-2 cascades, leading to cardioprotection against MI/R injury.

• OSTI ID: 23125196
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 500; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ACETYLCHOLINE
ANOXIA
ISCHEMIA
MITOCHONDRIA
RATS
RECEPTORS