Adiponectin inhibits cardiac arrest/cardiopulmonary resuscitation‑induced apoptosis in brain by increasing autophagy involved in AdipoR1‑AMPK signaling

He,Yarong; Liu,Bofu; Yao,Peng; Shao,Yuming; Cheng,Yanwei; Zhao,Jie; Wu,Jiang; Zhao,Zhi   Wei; Huang,Wen; Christopher,Theodore   A.; Lopez,Bernard; Ma,Xinliang; Cao,Yu

doi:10.3892/mmr.2020.11181

Adiponectin inhibits cardiac arrest/cardiopulmonary resuscitation‑induced apoptosis in brain by increasing autophagy involved in AdipoR1‑AMPK signaling

Authors:
- Yarong He
- Bofu Liu
- Peng Yao
- Yuming Shao
- Yanwei Cheng
- Jie Zhao
- Jiang Wu
- Zhi Wei Zhao
- Wen Huang
- Theodore A. Christopher
- Bernard Lopez
- Xinliang Ma
- Yu Cao
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Affiliations: Emergency Medicine Department, West China Hospital, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China, West China Clinical Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China, Laboratory of Ethnopharmacology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China, Emergency Medicine Department, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
Published online on: May 22, 2020 https://doi.org/10.3892/mmr.2020.11181
Pages: 870-878
Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Emerging evidence suggests that both apoptosis and autophagy contribute to global cerebral ischemia‑reperfusion (GCIR)‑induced neuronal death, which results from cardiac arrest (CA). However, the mechanism of how GCIR may affect the balance between apoptosis and autophagy resulting from CA remains to be elucidated. Additionally, the role of adiponectin (APN) in reversing the apoptosis and autophagy induced by GCIR following cardiac arrest‑cardiopulmonary resuscitation (CA‑CPR) is unclear. Thus, the aim of the present study was to investigate how GCIR affect the apoptosis and autophagy in response to CA and to clarify whether APN may alter the apoptosis and autophagy of neuronal death in GCIR‑injured brain post‑CA‑CPR. Using normal controls (Sham group) and two experimental groups [CA‑CPR‑induced GCIR injury (PCAS) group and exogenous treatment with adiponectin post‑CA‑CPR (APN group)], it was demonstrated that both apoptosis and autophagy were observed simultaneously in the brain subjected to GCIR, but apoptosis appeared to be more apparent. Exogenous administration of APN significantly reduced the formation of malondialdehyde, a marker of oxidative stress and increased the expression of superoxide dismutase, an anti‑oxidative enzyme, resulting in the stimulation of autophagy, inhibition of apoptosis and reduced brain tissue injury (P<0.05 vs. PCAS). APN treatment increased the expression of APN receptor 1 (AdipR1) and the phosphorylation of AMP‑activated protein kinase (AMPK; Ser182) in brain tissues. In conclusion, GCIR induced apoptosis and inhibited autophagy, contributing to brain injury in CA‑CPR. By contrast, APN reduced the brain injury by reversing the changes of neuronal autophagy and apoptosis induced by GCIR. The possible mechanism might owe to its effects on the activation of AMPK after combining with AdipR1 on neurons, which suggests a novel intervention against GCIR injury in CA‑CPR conditions.

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