Potential role of the cAMP/PKA/CREB signalling pathway in hypoxic preconditioning and effect on propofol‑induced neurotoxicity in the hippocampus of neonatal rats

Guan,Ruicong; Lv,Jing; Xiao,Fei; Tu,Youbing; Xie,Yubo; Li,Li

doi:10.3892/mmr.2019.10397

Potential role of the cAMP/PKA/CREB signalling pathway in hypoxic preconditioning and effect on propofol‑induced neurotoxicity in the hippocampus of neonatal rats

Authors:
- Ruicong Guan
- Jing Lv
- Fei Xiao
- Youbing Tu
- Yubo Xie
- Li Li
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Affiliations: Department of Anaesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China
Published online on: June 19, 2019 https://doi.org/10.3892/mmr.2019.10397
Pages: 1837-1845
Copyright: © Guan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hypoxic preconditioning (HPC) is neuroprotective against ischaemic brain injury; however, the roles of potential anti‑apoptotic signals in this process have not been assessed. To elucidate the molecular mechanisms involved in HPC‑induced neuroprotection, the effects of HPC on the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP response element‑binding protein (CREB) signalling pathway and apoptosis in Sprague‑Dawley pups (postnatal day 7) treated with propofol were investigated. Western blot and histological analyses demonstrated that HPC exerts multiple effects on the hippocampus, including the upregulation of cAMP and phosphorylation of CREB. These effects were partially blocked by intracerebroventricular injection of the protein kinase antagonist H89 (5 µmol/5 µl). Notably, the level of cleaved caspase‑3 was significantly downregulated by treatment with the cAMP agonist Sp‑cAMP (20 nmol/5 µl). The results indicate that propofol increased the level of cleaved caspase‑3 and Bax by suppressing the activity of cAMP‑dependent proteins and Bcl‑2; thus, HPC prevents propofol from triggering apoptosis via the cAMP/PKA/CREB signalling pathway.

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