Original Article

TRAIL-induced death of human adult oligodendrocytes is mediated by JNK pathway

  1. Anna Jurewicz1,
  2. Mariola Matysiak1,
  3. Stanisław Andrzejak2,
  4. Krzysztof Selmaj1,*

Article first published online: 3 OCT 2005

DOI: 10.1002/glia.20249

Issue

Glia

Glia

Volume 53, Issue 2, pages 158–166, 15 January 2006

Additional Information

How to Cite

Jurewicz, A., Matysiak, M., Andrzejak, S. and Selmaj, K. (2006), TRAIL-induced death of human adult oligodendrocytes is mediated by JNK pathway. Glia, 53: 158–166. doi: 10.1002/glia.20249

Author Information

  1. 1

    Department of Neurology, Medical University of Lodz, Lodz, Poland

  2. 2

    Department of Neurosurgery, Medical University of Lodz, Lodz, Poland

*Department of Neurology, Medical University of Lodz, 22 Kopcinskiego Str., 90-153 Lodz, Poland

Publication History

  1. Issue published online: 23 NOV 2005
  2. Article first published online: 3 OCT 2005
  3. Manuscript Accepted: 1 JUN 2005
  4. Manuscript Received: 7 MAR 2005

Funded by

  • Komitet Badan Naukowych (KBN). Grant Numbers: 3P05A03123, 3PO5A04425
  • Medical University (MU). Grant Number: 502-11-259
  • Center of Excellence

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (1021K)

Keywords:

  • oligodendrocyte;
  • mitochondrial membrane potential;
  • apoptosis;
  • multiple sclerosis

Abstract

Tumor necrosis-related apoptosis-inducing ligand (TRAIL) induces apoptosis of oligodendrocytes, target cells of immune attack in multiple sclerosis (MS). TRAIL-induced human oligodendrocyte (hOL) death depends on TRAIL ligation with its receptor 1 (TRAIL-R1). However, the intracellular signaling initiated with ligation of TRAIL-R1 in hOLs is unknown. We defined that intracellular transduction signaling involved in TRAIL-induced death of hOLs is associated with strong activation of c-jun NH2-terminal kinase (JNK) and a dominant negative mutant of MKK4/SEK1, MAP kinase upstream of JNK, inhibited TRAIL-induced apoptosis of hOLs. The immunoprecipitation experiments showed that JNK3 isoform was predominantly activated upon hOLs exposure to TRAIL and JNK-3 activation occurred before mitochondrial membrane dysfunction. The other mitogen-activated protein kinase p38 and ERK, as well as calpains and serine proteases, were not activated during TRAIL-induced hOL death. Accordingly, the calpain inhibitor, ZLLY.FMK, p38 kinase inhibitor, SB 203580, and serine proteases inhibitor, TPCK, did not protect hOLs from TRAIL-induced apoptosis. These results demonstrate that JNK pathway is critically involved in hOL death induced by TRAIL and might have significant importance in designing new molecules to protect immune-mediated hOLs demise. © 2005 Wiley-Liss, Inc.

View Full Article (HTML) Get PDF (1021K)