Nonenzymatic glycosylation of laminin and the laminin peptide CIKVAVS inhibits neurite outgrowth

Howard J. Federoff, Donald Lawrence, Michael Brownlee

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Nerve regeneration in diabetic animals is delayed and qualitatively impaired, but the mechanisms responsible for these defects have not been elucidated. The extracellular matrix protein laminin promotes the extension of neuronal processes, and recent studies have localized neurite-promoting activity to a lysine-containing sequence (IKVAV) within the laminin molecule. Because long-lived molecules such as laminin are likely to accumulate excessive amounts of nonenzymatic glycosylation products in diabetic subjects, we have investigated whether such adduct formation on laminin or the IKVAV peptide affects their neurite-promoting properties. These studies used the murine neuroblastoma cell line NB2a, which extends neurites on laminin when differentiated by cAMP. Neurite outgrowth in NB2a cells plated on glycosylated laminin was significantly decreased from that occurring on unmodified laminin. Similarly, neurite outgrowth in NB2a cells plated on glycosylated IKVAV peptide was inhibited compared with that observed on native IKVAV. These data suggest that nonenzymatic glycosylation of a biologically active domain within laminin may contribute to impaired nerve regeneration in diabetes.

Original languageEnglish (US)
Pages (from-to)509-513
Number of pages5
JournalDiabetes
Volume42
Issue number4
DOIs
StatePublished - Apr 1993

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Fingerprint Dive into the research topics of 'Nonenzymatic glycosylation of laminin and the laminin peptide CIKVAVS inhibits neurite outgrowth'. Together they form a unique fingerprint.

  • Cite this