Heparin-stimulated expression of extracellular-superoxide dismutase in human fibroblasts.
Extracellular-superoxide dismutase (EC-SOD) is the major SOD isozyme in the arterial wall and may be important for antioxidation capability of the vascular wall and normal vascular function. EC-SOD is expressed in various cell types in the vascular wall such as fibroblasts, smooth muscle cells and macrophages, and the synthesis of EC-SOD by human fibroblasts is known to be highly responsive to various inflammatory cytokines, although there is no response to oxidative stress. Heparin is a highly sulfated glycosaminoglycan with many functions such as antithrombotic, antilipemic and antiatherosclerotic effects. Another less well-known function of heparin is regulation of protein synthesis. In this study, we measured the induction of EC-SOD after treatment with heparin to understand the role of heparin in the antiatherosclerotic response of fibroblasts. Heparin induced EC-SOD expression at both the mRNA and protein levels. Heparin showed the greatest stimulatory effect and heparan sulfate showed moderate effects. The effect of chondroitin sulfate A was not clear. In contrast, desulfated heparin and chondroitin sulfate C did not increase EC-SOD expression. The stimulatory effect seemed to increase roughly with the degree of glycosaminoglycan sulfation. The enhanced expression of EC-SOD by heparin must contribute to the antiatherosclerotic effect of heparin.
Adachi
T
T
Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, 502-8585, Gifu, Japan. adachi@gifu-pu.ac.jp
Hara
H
H
Yamada
H
H
Yamazaki
N
N
Yamamoto
M
M
Sugiyama
T
T
Futenma
A
A
Katagiri
Y
Y
D001483:Base Sequence; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D011336:Probability; D012313:RNA / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D012680:Sensitivity and Specificity; D013482:Superoxide Dismutase / Q000378:metabolism*
D012333:RNA, Messenger; D012313:RNA; D006493:Heparin; D013482:Superoxide Dismutase