Research Article| Volume 56, 103221, November 2021

Vitamin D3 and estradiol alter PAD2 expression and activity levels in C6 glioma cells

Published:August 22, 2021DOI:


      • Vitamin D reduced the PAD2 enzyme activity in C6 glioma cells.
      • Vitamin D reduced the PAD2 expression levels in C6 glioma cells.
      • Estradiol increased the PAD2 enzyme activity in C6 glioma cells.
      • Estradiol increased the PAD2 expression levels in C6 glioma cells.


      Multiple Sclerosis (MS) is known as a chronic demyelinating disease with multifactorial etiology. It is suggested that the deimination of myelin basic proteins (MBPs) by peptidyl arginine deiminase 2 (PAD2) may increase citrulline residues resulting in the reduction of myelin sheath density and the progression of multiple sclerosis. The aim of this study was to investigate the effects of vitamin D (25-hydroxy cholecalciferol (D3)) and estradiol on PAD2 gene expression level and its catalytic activity in rat C6 glioma cells. C6 glioma cells were cultured in DMEM medium and were treated with vitamin D (10 and 100 ng/ml) and estradiol (10 and 100 µM) based on the cellular viability. Then, the PAD2 gene expression and catalytic activity were evaluated using real-time qRT-PCR and spectrophotometry techniques, respectively. The PAD2 gene expression level and its catalytic activity increased significantly in estradiol-treated cells (P = 0.0435 and P = 0.0015, respectively). Conversely, vitamin D downregulated significantly the PAD2 gene expression level (P < 0.015) and its activity (P < 0.017). The study results suggested that estradiol conversely with vitamin D increases the activity of the PAD2 enzyme so that it might develop multiple sclerosis, especially in women.


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