Upregulation of Connexin-43 is Critical for Irradiation-induced Neuroinflammation.

Abstract

BACKGROUND:

Radiation therapy is widely used for the treatment of pituitary adenomas. Unfortunately, it might raise the risk of ischemic stroke, with neuroinflammation being a major pathological process. Astrocytes are the most abundant cell type in the central nervous system and have been reported for playing important roles in ischemic stroke.

OBJECTIVE:

Here we studied how γ-radiation would introduce astrocytes into a detrimental state for neuroinflammation and provide new theory evidence and target for the clinical management of inflammation- related neural damage after radiation-induced ischemic stroke.

METHOD:

HA-1800 cells were treated with γ-radiation and then the protein and mRNA levels of Connexin (Cx)-43 were evaluated by western and q-PCR. The culture supernatant was collected and the concentrations of the inflammatory factors were determined by ELISA. MiRNA complementary to Cx-43 was designed through the online tools.

RESULTS:

Cx-43 is upregulated in the treatment of γ-radiation in astrocytes and γ-radiation introduced the detrimental function of astrocytes: cell viability was reduced while the apoptotic cells were increased. Inflammatory factors like tumor necrosis factor alpha, interferon gamma, interleukin-6, interleukin 1-beta were dramatically up-regulated by the irradiation. MiR-374a rescued irradiation induced Cx-43 up-regulation of astrocytes and eliminated detrimental function triggered by γ-radiation.

CONCLUSION:

Cx-43 expression level may play an important role in the inflammation-related neural damage after irradiation-induced ischemic stroke.

• Authors: Wei Chen, Wusong Tong, Yijun Guo, Bin He, Lei Chen, Wenjin Yang, Chenxing Wu, Dabin Ren, Ping Zheng, Jiugeng Feng
• Journal: CNS & neurological disorders drug targets (CNS Neurol Disord Drug Targets) Vol. 17 Issue 7 Pg. 539-546 ( 2018) ISSN: 1996-3181 [Electronic] United Arab Emirates
• PMID: 29984671 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

Chemical References

• Connexin 43
• Cytokines
• GJA1 protein, human
• Glial Fibrillary Acidic Protein
• RNA, Messenger

Topics

• Apoptosis (radiation effects)
• Cell Line, Transformed
• Cell Proliferation (radiation effects)
• Connexin 43 (genetics, metabolism)
• Cytokines (genetics, metabolism)
• Gamma Rays
• Glial Fibrillary Acidic Protein (metabolism)
• Humans
• Neuroglia (metabolism, radiation effects)
• RNA, Messenger (metabolism)
• Up-Regulation (radiation effects)