Skip Navigation


Brain Advance Access originally published online on October 11, 2005
Brain 2005 128(11):2675-2688; doi:10.1093/brain/awh627
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
128/11/2675    most recent
awh627v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (16)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Jurewicz, A.
Right arrow Articles by Selmaj, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jurewicz, A.
Right arrow Articles by Selmaj, K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author (2005). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Tumour necrosis factor-induced death of adult human oligodendrocytes is mediated by apoptosis inducing factor

Anna Jurewicz1, Mariola Matysiak1, Krzysztof Tybor2, Lukasz Kilianek3, Cedric S. Raine4 and Krzysztof Selmaj1

Departments of 1 Neurology and 2 Neurosurgery, Medical University of Lodz, Lodz, Poland, 3 Nencki Institute of Experimental Biology, Warsaw and 4 Department of Pathology (Neuropathology), Albert Einstein College of Medicine, Bronx, NY, USA

Correspondence to: Krzysztof Selmaj, MD, PhD, Department of Neurology, Medical University of Lodz, ul. Kopcinskiego 22, 90-153 Lodz, Poland E-mail: kselmaj{at}afazja.am.lodz.pl

Tumour necrosis factor (TNF)-induced death of oligodendrocytes, the cell type targeted in multiple sclerosis, is mediated by TNF receptor p55 (TNFR-p55). The ligation of TNFR-p55 induces several signal transduction pathways; however, the precise mechanism involved in human oligodendrocyte (hOL) death is unknown. We defined that TNF-induced death of hOLs is non-caspase dependent, as evidenced by lack of generation of caspases 8, 1 and 3 active subunits; lack of cleavage of caspases 1 and 3 fluorogenic substrates; and lack of hOL death inhibition by the general caspase inhibitor, ZVAD.FMK. Electrophoresis of TNF-exposed hOL DNA revealed large-scale DNA fragmentation characteristic of apoptosis-inducing factor (AIF)-mediated cell death, and co-localization experiments showed that AIF translocation to the nucleus occurred upon exposure to TNF. AIF depletion by an antisense strategy prevented TNF-induced hOL death. These results indicate that TNF-induced death of hOLs is dependent on AIF, information of significance for the design strategies to protect hOLs during immune-mediated demyelination.

Key Words: oligodendrocytes; apoptosis inducing factor; multiple sclerosis; cell death

Abbreviations: AIF = apoptosis-inducing factor; anti-GFAP = anti-glial fibrillary acidic protein; anti-MBP = anti-myelin basic protein; asAIF = antisense AIF; FACS = fluorescence-activated cell sorter; FADD = Fas-associated protein with death domain; hOL = human oligodendrocyte; OL = oligodendrocyte; PI = propidium iodide; TNF = tumour necrosis factor; TNFR-p55 = TNF receptor p55; TPCK = N-tosyl-L-phenylalanine chloromethyl ketone; TRADD = TNF-R1-associated death domain

Received March 31, 2005. Revised June 25, 2005. Accepted August 1, 2005.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
H. Degens, A. K. Swisher, Y. F. Heijdra, P. M. Siu, P. N. Richard Dekhuijzen, and S. E. Alway
Apoptosis and Id2 expression in diaphragm and soleus muscle from the emphysematous hamster
Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R135 - R144.
[Abstract] [Full Text] [PDF]

Home page
 NeuroscientistHome page
O. Aktas, T. Prozorovski, and F. Zipp
Death Ligands and Autoimmune Demyelination
Neuroscientist, August 1, 2006; 12(4): 305 - 316.
[Abstract] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.