Brevican is degraded by matrix metalloproteinases and aggrecanase-1 (ADAMTS4) at different sites

Hiroyuki Nakamura, Yutaka Fujii, Isao Inoki, Kotaro Sugimoto, Kazuhiko Tanzawa, Hirokazu Matsuki, Ryu Miura, Yu Yamaguchi, Yasunori Okada

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

Brevican is a member of the lectican family of chondroitin sulfate proteoglycans that is predominantly expressed in the central nervous system. The susceptibility of brevican to digestion by matrix metalloproteinases (MMP-1, -2, -3, -7, -8, -9, -10, and -13 and membrane type 1 and 3 MMPs) and aggrecanase-1 (ADAMTS4) was examined. MMP-1, -2, -3, -7, -8, -10, and -13 degraded brevican into a few fragments with similar molecular masses, whereas the degradation products of aggrecanase-1 had apparently different sizes. NH2-terminal sequence analyses of the digestion fragments revealed that cleavages of the brevican core protein by these metalloproteinases occurred commonly within the central non-homologous domain. MMP-1, -2, -3, -7, -8, -10, and -13 preferentially attacked the Ala360-Phe361 bond, whereas aggrecanase-1 cleaved the Glu395-Ser396 bond, which are similar to the cleavage sites observed with cartilage proteoglycan (aggrecan) for the MMPs and aggrecanase-1, respectively. These data demonstrate that MMP-1, -2, -3, -7, -8, -10, and -13 and aggrecanase-1 digest brevican in a similar pattern to aggrecan and suggest that they may be responsible for the physiological turnover and pathological degradation of brevican.

Original languageEnglish
Pages (from-to)38885-38890
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number49
DOIs
Publication statusPublished - 2000 Dec 8

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Brevican is degraded by matrix metalloproteinases and aggrecanase-1 (ADAMTS4) at different sites'. Together they form a unique fingerprint.

  • Cite this

    Nakamura, H., Fujii, Y., Inoki, I., Sugimoto, K., Tanzawa, K., Matsuki, H., Miura, R., Yamaguchi, Y., & Okada, Y. (2000). Brevican is degraded by matrix metalloproteinases and aggrecanase-1 (ADAMTS4) at different sites. Journal of Biological Chemistry, 275(49), 38885-38890. https://doi.org/10.1074/jbc.M003875200