Transcriptional Regulation of Human Transforming Growth Factor-α in Astrocytes.

Molecular Neurobiology
Pratap KarkiEunsook Lee

Abstract

Transforming growth factor-alpha (TGF-α) is known to play multifunctional roles in the central nervous system (CNS), including the provision of neurotropic properties that protect neurons against various neurotoxic insults. Previously, we reported that TGF-α mediates estrogen-induced enhancement of glutamate transporter GLT-1 function in astrocytes. However, the regulatory mechanism of TGF-α at the transcriptional level remains to be established. Our findings revealed that the human TGF-α promoter contains consensus sites for several transcription factors, such as NF-κB and yin yang 1 (YY1). NF-κB served as a positive regulator of TGF-α promoter activity, corroborated by observations that overexpression of NF-κB p65 increased, while mutation in the NF-κB binding sites in the TGF-α promoter reduced the promoter activity in rat primary astrocytes. Pharmacological inhibition of NF-κB with pyrrolidine dithiocarbamate (PDTC; 50 μM) or quinazoline (QNZ; 10 μM) also abolished TGF-α promoter activity, and NF-κB directly bound to its consensus site in the TGF-α promoter as evidenced by electrophoretic mobility shift assay (EMSA). Dexamethasone (DX) increased TGF-α promoter activity by activation of NF-κB. Treatment of astrocytes with 10...Continue Reading

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Citations

Nov 18, 2018·Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology·Nils Kristian PrenzlerAthanasia Warnecke
Aug 28, 2018·Case Reports in Ophthalmological Medicine·Emilio CamposMarina Buzzi
May 16, 2018·Drug Delivery and Translational Research·Nils K PrenzlerAthanasia Warnecke
Sep 25, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Li-Yu WangCheng-Hung Chuang
Dec 3, 2020·Frontiers in Oncology·Tianhao ZhuSibo Zhu
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Shankargouda Patil, Luca Testarelli
May 25, 2021·Alzheimer's & Dementia : Translational Research & Clinical Interventions·Qiliang HeAnnabelle C Singer
May 16, 2021·Neuropharmacology·Ada G Rodríguez-Campuzano, Arturo Ortega

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Methods Mentioned

BETA
transfection
PCR
protein assay
nuclear translocation

Software Mentioned

GraphPad Prism

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