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Comp Biochem Physiol C Toxicol Pharmacol. 2019 Mar;217:68-75. doi: 10.1016/j.cbpc.2018.11.018. Epub 2018 Nov 27.

A novel mechanism of Gamma-aminobutyric acid (GABA) protecting human umbilical vein endothelial cells (HUVECs) against H2O2-induced oxidative injury.

Author information

1
Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, China; Center for Southern Economic Crops, Chinese Academy of Agricultural Sciences, China.
2
Huayuan Tianle Fu Agriculture Technology Co. Ltd., China.
3
Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, China; Center for Southern Economic Crops, Chinese Academy of Agricultural Sciences, China. Electronic address: ibfczzh@126.com.

Abstract

Vascular endothelial cell damage is related to many vascular diseases, including cardiovascular disease (CVD). Reactive oxygen species (ROS) play a vital role in the pathogenesis of many cardiovascular diseases. Herein, H2O2-induced human umbilical vein endothelial cell (HUVEC) injury model was used to explore the mechanisms involved in the pathogenesis of ROS-induced oxidative stress and cell dysfunction. Gamma-aminobutyric acid (GABA), a naturally occurring four-carbon non-protein amino acid, has antioxidant activity and anti-inflammatory action. In the present study, we demonstrated that GABA could scavenge free radicals including DPPH and ABTS, reverse H2O2-induced suppression on HUVEC proliferation, HUVEC apoptosis and ROS formation via p65 signaling. Interestingly, GABA treatment alone did not cause significant changes in p65 phosphorylation, suggesting that GABA will not cause imbalance in NF-κB signaling and ROS formation without oxidative stress. Moreover, GABA also modulated Keap1-Nrf2 and Notch signaling pathways upon H2O2 stimulation, suggesting that GABA may exert its effect via multi mechanisms. In conclusion, the present study demonstrated that GABA inhibits H2O2-induced oxidative stress in HUVECs via inhibiting ROS-induced NF-κB and Caspase 3 pathway activation. GABA may, therefore, have potential as a pharmacological agent in the prevention or treatment of oxidative injury-related cardiovascular disease.

KEYWORDS:

Gamma-aminobutyric acid (GABA); Human umbilical vein endothelial cell (HUVEC); NF-κB signaling pathway; Oxidative injury; Reactive oxygen species (ROS)

PMID:
30500452
DOI:
10.1016/j.cbpc.2018.11.018
[Indexed for MEDLINE]

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