Fundamental Toxicological Sciences

Paper Details

Fundamental Toxicological Sciences
Vol. 7 No. 2 March 03, 2020 p.77-83
Original Article
Arsenite inhibits gene expression of perlecan, syndecan-1, -2, -3 and biglycan in cultured vascular endothelial cells
  • Toshiyuki Kaji (Department of Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science / t-kaji@rs.tus.ac.jp)
  • Yasuyuki Fujiwara (Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences / yasuyuki@toyaku.ac.jp)
Dong-pan Wu 1) 2) , Tsuyoshi Nakano 1) , Yayoi Tsuneoka 1) , Tsutomu Takahashi 1) , Yo Shinoda 1) , Toshiyuki Kaji 3) , Yasuyuki Fujiwara 1)
1) Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences , 2) Department of Pharmacy, Guang’ anmen Hospital of China Academy of Chinese Medical Sciences, China , 3) Department of Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science
Keywords: Arsenite, Proteoglycan, Perlecan, Biglycan, Vascular endothelial cell
Abstracts

Arsenic is an environmental pollutant and is a possible risk factor for vascular diseases such as atherosclerosis. Vascular proteoglycans (PGs) are key molecules in the initiation and progression of atherosclerosis. We previously demonstrated that arsenite, but not arsenate, decreases the synthesis of both heparan sulfate proteoglycans (HSPGs) and chondroitin/dermatan sulfate proteoglycans (CS/DSPGs) in cultured vascular endothelial cells. In the present study, we aimed to identify the PG molecules whose expression is decreased by arsenite, using a culture system of bovine aortic endothelial cells. The results indicate that a 24-hr treatment of arsenite significantly decreases the mRNA levels of a large HSPG perlecan, small HSPGs—syndecan-1, -2 and -3—, and a small CS/DSPG biglycan in vascular endothelial cells without nonspecific cell damage; the expression of syndecan-4 mRNA was unaffected by arsenite. The decreased expression of perlecan, syndecan-1 and biglycan genes began after 3 hr of arsenite treatment. However, arsenate did not change the mRNA expression levels of perlecan and biglycan in the cells. These results suggest that the inhibition of synthesis by arsenite occurs in particular types of proteoglycans, i.e. perlecan, syndecan-1, -2, -3, and biglycan in vascular endothelial cells.