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Caspase‐3 activation in oligodendrocytes from the myelin‐deficient rat
Author(s) -
Beesley Jacqueline S.,
Lavy LeaAnn,
Eraydin Nuri B.,
Siman Robert,
Grinspan Judith B.
Publication year - 2001
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.1088
Subject(s) - oligodendrocyte , galactocerebroside , proteolipid protein 1 , myelin , myelin basic protein , microbiology and biotechnology , biology , mutant , programmed cell death , chemistry , apoptosis , biochemistry , gene , neuroscience , central nervous system
The myelin‐deficient (MD) rat has a point mutation in its proteolipid protein (PLP) gene that causes severe dysmyelination and oligodendrocyte cell death. Using an in vitro model, we have shown that MD oligodendrocytes initially differentiate similarly to wild‐type cells, expressing galactocerebroside, 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase, and myelin basic protein. However, at the time when PLP expression would normally begin, the MD oligodendrocytes die via an apoptotic pathway involving caspase activation. The active form of caspase‐3 was detected, along with the cleavage products of poly‐(ADP‐ribose) polymerase (PARP) and spectrin, major targets of caspase‐mediated proteolysis. A specific inhibitor of casapse‐3, Ac‐DEVD‐CMK, reduced apoptosis in MD oligodendrocytes, but the rescued cells did not mature fully or express myelin‐oligodendrocyte glycoprotein. These results suggest that mutant PLP affects not only cell death but also oligodendrocyte differentiation. J. Neurosci. Res. 64:371–379, 2001. © 2001 Wiley‐Liss, Inc.