Suppression of GRASP65 phosphorylation by tetrahydrocurcumin protects against cerebral ischemia/reperfusion injury via ERK signaling

Lin,Bin; Yu,Heng; Lin,Yuting; Cai,Chao; Lu,Huoquan; Zhu,Xinbo

doi:10.3892/mmr.2016.5816

Suppression of GRASP65 phosphorylation by tetrahydrocurcumin protects against cerebral ischemia/reperfusion injury via ERK signaling

Authors:
- Bin Lin
- Heng Yu
- Yuting Lin
- Chao Cai
- Huoquan Lu
- Xinbo Zhu
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Affiliations: Department of Pharmacy, Changxing People's Hospital of Zhejiang, Huzhou, Zhejiang 313100, P.R. China, Department of Medicine, First Clinical Medicine School, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China, Department of Medicine, Renji School, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China, Department of Pharmacy, Pharmacy School, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China
Published online on: October 6, 2016 https://doi.org/10.3892/mmr.2016.5816
Pages: 4775-4780

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Abstract

The aim of the present study was to assess the neuroprotective effects of tetrahydrocurcumin (THC) in a mouse model of cerebral ischemia/reperfusion (I/R) injury, and to investigate the involvement of Golgi reassembly and stacking protein 65 (GRASP65) and the extracellular signal‑regulated kinase (ERK) signaling pathway. Cerebral I/R injury was induced using the Pulsinelli four‑vessel occlusion method. After 5 min of reperfusion, mice received THC (5, 10 or 25 mg/kg) or saline by intraperitoneal injection. After 24 h of reperfusion, mice underwent neurological evaluation. Infarct volumes were determined by triphenyltetrazolium chloride staining, and levels of superoxide dismutase and malondialdehyde were measured in brain tissue homogenates. Expression of GRASP65, phosphorylated‑GRASP65, ERK and phosphorylated‑ERK was determined by western blotting. THC induced a dose‑dependent decrease in the phosphorylation of ERK and GRASP65. Thus, THC attenuated I/R injury‑induced activation of the ERK signaling pathway and reduced the phosphorylation of GRASP65. THC exhibited a dose‑dependent protective effect against cerebral I/R injury, mediated by suppression of the ERK signaling pathway and a subsequent reduction in GRASP65 phosphorylation. The current study provided new information in the research of the cerebral ischemia‑reperfusion injury mechanism.

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