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 Citations (Scopus)

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
StatePublished - Apr 1993
Externally publishedYes

Fingerprint

Laminin
isoleucyl-lysyl-valyl-alanyl-valine
Glycosylation
Peptides
Neurites
Nerve Regeneration
Neuronal Outgrowth
Extracellular Matrix Proteins
Neuroblastoma
Lysine
Cell Line

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Federoff, H. J., Lawrence, D., & Brownlee, M. (1993). Nonenzymatic glycosylation of laminin and the laminin peptide CIKVAVS inhibits neurite outgrowth. Diabetes, 42(4), 509-513.

Nonenzymatic glycosylation of laminin and the laminin peptide CIKVAVS inhibits neurite outgrowth. / Federoff, Howard J.; Lawrence, Donald; Brownlee, Michael.

In: Diabetes, Vol. 42, No. 4, 04.1993, p. 509-513.

Research output: Contribution to journalArticle

Federoff, HJ, Lawrence, D & Brownlee, M 1993, 'Nonenzymatic glycosylation of laminin and the laminin peptide CIKVAVS inhibits neurite outgrowth', Diabetes, vol. 42, no. 4, pp. 509-513.
Federoff, Howard J. ; Lawrence, Donald ; Brownlee, Michael. / Nonenzymatic glycosylation of laminin and the laminin peptide CIKVAVS inhibits neurite outgrowth. In: Diabetes. 1993 ; Vol. 42, No. 4. pp. 509-513.
@article{61edd5ad13b14151b11139d3d20a48e7,
title = "Nonenzymatic glycosylation of laminin and the laminin peptide CIKVAVS inhibits neurite outgrowth",
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.",
author = "Federoff, {Howard J.} and Donald Lawrence and Michael Brownlee",
year = "1993",
month = "4",
language = "English (US)",
volume = "42",
pages = "509--513",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "4",

}

TY - JOUR

T1 - Nonenzymatic glycosylation of laminin and the laminin peptide CIKVAVS inhibits neurite outgrowth

AU - Federoff, Howard J.

AU - Lawrence, Donald

AU - Brownlee, Michael

PY - 1993/4

Y1 - 1993/4

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0027537291&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027537291&partnerID=8YFLogxK

M3 - Article

C2 - 8454100

AN - SCOPUS:0027537291

VL - 42

SP - 509

EP - 513

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 4

ER -