Cadmium induces chondroitin sulfate synthase 1 via protein kinase Cα and elongates chondroitin/dermatan sulfate chains in cultured vascular endothelial cells

Takato Hara; Shogo Matsuura; Keita Aikawa; Misaki Shirai; Mai Yoshida; Toshiyuki Kaji; Chika Yamamoto

doi:10.2131/jts.48.457

Original Article

Cadmium induces chondroitin sulfate synthase 1 via protein kinase Cα and elongates chondroitin/dermatan sulfate chains in cultured vascular endothelial cells

Takato Hara, Shogo Matsuura, Keita Aikawa, Misaki Shirai, Mai Yoshida, Toshiyuki Kaji, Chika Yamamoto

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Keywords: Vascular endothelial cell, Cadmium, Proteoglycan, Chondroitin sulfate synthase 1, Chondroitin/dermatan sulfate

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2023 Volume 48 Issue 8 Pages 457-467

DOI https://doi.org/10.2131/jts.48.457

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Abstract

Cadmium is an environmental pollutant and a risk factor for atherosclerosis. In the atherosclerotic intima, dermatan sulfate chains accelerate accumulation and oxidation of LDL cholesterol. The major type of dermatan sulfate proteoglycan that is synthesized by vascular endothelial cells is biglycan. In the present study, we analyzed the effect of cadmium on the biglycan synthesis using cultured bovine aortic endothelial cells. Cadmium did not induce biglycan mRNA and core protein expression; however, it elongated the chondroitin/dermatan sulfate chains of biglycan. Among elongation enzymes of the chondroitin/dermatan sulfate chain, chondroitin sulfate synthase 1 (CHSY1) mRNA and protein expression were dose- and time-dependently upregulated by cadmium depending on protein kinase Cα. This finding suggests that CHSY1-dependent elongation of chondroitin/dermatan sulfate chains of biglycan may exacerbate cadmium-induced atherosclerosis.

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