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Grape Seed Proanthocyanidins Protect N2a Cells against Ischemic Injury via Endoplasmic Reticulum Stress and Mitochondrial-associated Pathways

[ Vol. 18 , Issue. 4 ]

Author(s):

Kun Fu, Liqiang Chen, Lifeng Miao*, Yan Guo, Wei Zhang and Yunan Bai*   Pages 334 - 341 ( 8 )

Abstract:


Background/Objective: Grape seed proanthocyanidins (GSPs) are a group of polyphenolic bioflavonoids, which possess a variety of biological functions and pharmacological properties. We studied the neuroprotective effects of GSP against oxygen-glucose deprivation/reoxygenation (OGD/R) injury and the potential mechanisms in mouse neuroblastoma N2a cells.

Methods: OGD/R was conducted in N2a cells. Cell viability was evaluated by CCK-8 and LDH release assay. Apoptosis was assessed by TUNEL staining and flow cytometry. Protein levels of cleaved caspase-3, Bax and Bcl-2 were detected by Western blotting. CHOP, GRP78 and caspase-12 mRNA levels were assessed by real-time PCR. JC-1 dying was used to detect mitochondrial membrane potential. ROS levels, activities of endogenous antioxidant enzymes and ATP production were examined to evaluate mitochondrial function.

Results: GSP increased cell viability after OGD/R injury in a dose-dependent manner. Furthermore, GSP inhibited cell apoptosis, reduced the mRNA levels of CHOP, GRP78 and caspase-12 (ER stressassociated genes), restored mitochondrial membrane potential and ATP generation, improved activities of endogenous anti-oxidant ability (T-AOC, GXH-Px, and SOD), and decreased ROS level.

Conclusion: Our findings suggest that GSP can protect N2a cells from OGD/R insult. The mechanism of anti-apoptotic effects of GSP may involve attenuating ER stress and mitochondrial dysfunction.

Keywords:

Grape seed proanthocyanidins, oxygen-glucose deprivation/reoxygenation, apoptosis, endoplasmic reticulum stress, mitochondrial dysfunction, brain ischemia.

Affiliation:

Department of Neurosurgery, Yidu Central Hospital of Weifang, Qingzhou 262500, Shandong, Department of Neurosurgery, Yidu Central Hospital of Weifang, Qingzhou 262500, Shandong, Department of Neurosurgery, Dezhou People's Hospital, Dezhou 253014, Shandong, Department of Internal Medicine, Qingzhoushi People's Hospital, Qingzhou 262500 Shandong, Department of Neurosurgery, Yidu Central Hospital of Weifang, Qingzhou 262500, Shandong, Department of Neurosurgery, Yidu Central Hospital of Weifang, Qingzhou 262500, Shandong

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