GATA-4 regulates neuronal apoptosis after intracerebral hemorrhage via the NF-κB/Bax/Caspase-3 pathway both in vivo and in vitro.

Abstract

GATA-binding protein 4 (GATA-4)，a member of the GATA family of transcription factors, is expressed in the normal brain and participates in the neural inflammatory response and senescence. However, few studies have investigated whether GATA-4 is involved in the brain damage induced by intracerebral hemorrhage (ICH). The aim of this study was to investigate in vivo and in vitro the role of GATA-4 in ICH-induced secondary brain injury (SBI) and its potential underlying mechanisms. A rat model of ICH was established by autologous blood injection in vivo. In vitro, oxidized hemoglobin was applied to mimic the effects of ICH in neuronal culture. The function of GATA-4 and its mechanism of action after ICH were investigated using siRNA-mediated knockdown and plasmid-mediated overexpression techniques combined with immunofluorescence, western blot, and other molecular methods. It was found that the expression of GATA-4 was increased in the brain of rats after ICH, and its phosphorylation also increased correspondingly. Furthermore, knocking down the expression of GATA-4 led to a significant decrease in neurobehavioral scores and neuronal apoptosis, indicating that secondary brain damage was improved. Conversely, the overexpression of GATA-4 aggravated brain damage. Blockade of a critical phosphorylation site on the GATA-4 overexpression plasmid alleviated the exacerbated damage in vitro and in vivo. Moreover, GATA-4 promoted the activation of NF-κB, and increased the expression of Bax, and cysteine aspartate-specific protease 3 (caspase-3) in its cleaved form, causing neuronal apoptosis. In conclusion, the expression of GATA-4 was increased in the brain of rats after ICH. GATA-4 phosphorylation mediates the function of the protein in ICH-induced SBI. Neuronal apoptosis after ICH was mainly induced by NF-κB activation, which was promoted by GATA-4.

• Authors: Hui Xu, Jie Cao, Jianguo Xu, Haiying Li, Haitao Shen, Xiang Li, Zhong Wang, Jiang Wu, Gang Chen
• Journal: Experimental neurology (Exp Neurol) Vol. 315 Pg. 21-31 (05 2019) ISSN: 1090-2430 [Electronic] United States
• PMID: 30710529 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Bax protein, rat
• GATA4 Transcription Factor
• NF-kappa B
• bcl-2-Associated X Protein
• Casp3 protein, rat
• Caspase 3

Topics

• Animals
• Apoptosis (genetics)
• Behavior, Animal
• Brain Chemistry
• Caspase 3 (genetics)
• Cerebral Hemorrhage (metabolism, pathology)
• GATA4 Transcription Factor (biosynthesis, genetics)
• Gene Knockdown Techniques
• Male
• NF-kappa B (genetics)
• Neurons (pathology)
• Phosphorylation
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (genetics)
• bcl-2-Associated X Protein (genetics)