help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ye, P.
Right arrow Articles by D’Ercole, A. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ye, P.
Right arrow Articles by D’Ercole, A. J.
Endocrinology Vol. 140, No. 7 3063-3072
Copyright © 1999 by The Endocrine Society

ARTICLES

Insulin-Like Growth Factor I Protects Oligodendrocytes from Tumor Necrosis Factor-{alpha}-Induced Injury1

P. Ye and A. J. D’Ercole

Department of Pediatrics, CB 7220, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7220

Address all correspondence and requests for reprints to: Dr. A. J. D’Ercole, Department of Pediatrics, CB 7220, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7220.

Tumor necrosis factor-{alpha} (TNF-{alpha}) has been causally implicated in several demyelinating disorders, including multiple sclerosis. Because insulin-like growth factor I (IGF-I) is a potent stimulator of myelination, we investigated whether it can protect oligodendrocytes and myelination from TNF-{alpha}-induced damage using mouse glial cultures as a model. Compared with controls, TNF-{alpha} decreased oligodendrocyte number by approximately 40% and doubled the number of apoptotic oligodendrocytes and their precursors. Addition of Boc-aspartyl(Ome)-fluoromethyl ketone (BAF), an inhibitor of interleukin-1ß converting enzyme (ICE)/caspase proteases, blocked TNF-{alpha}-induced reductions in oligodendrocytes, indicating that the TNF-{alpha}-induced reduction in oligodendrocytes is, at least in part, due to apoptosis, and that ICE/caspases are one of TNF-{alpha} action mediators. Simultaneous addition of IGF-I to TNF-{alpha}-treated cultures negated these TNF-{alpha} effects nearly completely. Furthermore, IGF-I promoted oligodendrocyte precursor proliferation and/or differentiation in TNF-{alpha}-treated cultures. To analyze TNF-{alpha} and IGF-I actions on oligodendrocyte function, we measured the abundance of messenger RNAs (mRNAs) for two major myelin-specific proteins, myelin basic protein (MBP) and proteolipid protein (PLP). While TNF-{alpha} decreased MBP and PLP mRNA abundance by 5- to 6-fold, IGF-I abrogated TNF-{alpha}-induced reductions in a dose- and time-dependent manner. The changes in MBP and PLP mRNA abundance could not be completely explained by the changes in oligodendrocyte number, indicating that myelin protein gene expression is regulated by both TNF-{alpha} and IGF-I. These data support the hypothesis that TNF-{alpha} can mediate oligodendrocyte and myelin damage, and indicate that IGF-I protects oligodendrocytes from TNF-{alpha} insults by blocking TNF-{alpha}-induced apoptosis, and by promoting oligodendrocyte and precursor proliferation/differentiation and myelin protein gene expression.




This article has been cited by other articles:


Home page
 EndocrinologyHome page
A. Joseph D'Ercole and P. Ye
Expanding the Mind: Insulin-Like Growth Factor I and Brain Development
Endocrinology, December 1, 2008; 149(12): 5958 - 5962.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
F. G. Mastronardi, D. D. Wood, J. Mei, R. Raijmakers, V. Tseveleki, H.-M. Dosch, L. Probert, P. Casaccia-Bonnefil, and M. A. Moscarello
Increased Citrullination of Histone H3 in Multiple Sclerosis Brain and Animal Models of Demyelination: A Role for Tumor Necrosis Factor-Induced Peptidylarginine Deiminase 4 Translocation.
J. Neurosci., November 1, 2006; 26(44): 11387 - 11396.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
P. Mana, D. Linares, S. Fordham, M. Staykova, and D. Willenborg
Deleterious Role of IFN{gamma} in a Toxic Model of Central Nervous System Demyelination
Am. J. Pathol., May 1, 2006; 168(5): 1464 - 1473.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
P. H. Larsen, A. G. DaSilva, K. Conant, and V. W. Yong
Myelin formation during development of the CNS is delayed in matrix metalloproteinase-9 and -12 null mice.
J. Neurosci., February 22, 2006; 26(8): 2207 - 2214.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
R. G. Smith, L. Betancourt, and Y. Sun
Molecular Endocrinology and Physiology of the Aging Central Nervous System
Endocr. Rev., April 1, 2005; 26(2): 203 - 250.
[Abstract] [Full Text] [PDF]

Home page
 Reproductive SciencesHome page
B. Feldhaus, I. D. Dietzel, R. Heumann, and R. Berger
Effects of Interferon-{gamma} and Tumor Necrosis Factor-{alpha} on Survival and Differentiation of Oligodendrocyte Progenitors
Reproductive Sciences, February 1, 2004; 11(2): 89 - 96.
[Abstract] [PDF]

Home page
 J. Neurosci.Home page
J. L. Mason, S. Xuan, I. Dragatsis, A. Efstratiadis, and J. E. Goldman
Insulin-Like Growth Factor (IGF) Signaling through Type 1 IGF Receptor Plays an Important Role in Remyelination
J. Neurosci., August 20, 2003; 23(20): 7710 - 7718.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. Moralez, W. H. Busby Jr., and D. Clemmons
Control of Insulin-Like Growth Factor Binding Protein-5 Protease Synthesis and Secretion by Human Fibroblasts and Porcine Aortic Smooth Muscle Cells
Endocrinology, June 1, 2003; 144(6): 2489 - 2495.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
E. Chaum and H. Yang
Transgenic Expression of IGF-1 Modifies the Proliferative Potential of Human Retinal Pigment Epithelial Cells
Invest. Ophthalmol. Vis. Sci., December 1, 2002; 43(12): 3758 - 3764.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
P. Ye, L. Li, R. G. Richards, R. P. DiAugustine, and A. J. D'Ercole
Myelination Is Altered in Insulin-Like Growth Factor-I Null Mutant Mice
J. Neurosci., July 15, 2002; 22(14): 6041 - 6051.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
D. Chrysis, A. S. Calikoglu, P. Ye, and A. J. D'Ercole
Insulin-Like Growth Factor-I Overexpression Attenuates Cerebellar Apoptosis by Altering the Expression of Bcl Family Proteins in a Developmentally Specific Manner
J. Neurosci., March 1, 2001; 21(5): 1481 - 1489.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
J. L. Mason, P. Ye, K. Suzuki, A. J. D'Ercole, and G. K. Matsushima
Insulin-Like Growth Factor-1 Inhibits Mature Oligodendrocyte Apoptosis during Primary Demyelination
J. Neurosci., August 1, 2000; 20(15): 5703 - 5708.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
B. R. Lackey, S. L. Gray, and D. M. Henricks
Does the Insulin-Like Growth Factor System Interact with Prostaglandins and Proinflammatory Cytokines During Neurodegeneration?
Experimental Biology and Medicine, May 1, 2000; 224(1): 20 - 27.
[Abstract] [Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1999 by The Endocrine Society