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The Journal of Neuroscience, September 15, 1998, 18(18):7047-7060
Identification of a Survival-Promoting Peptide in Medium
Conditioned by Oxidatively Stressed Cell Lines of Nervous System
Origin
Timothy J.
Cunningham1,
Lisa
Hodge1,
David
Speicher2,
Dave
Reim2,
Carla
Tyler-Polsz1,
Pat
Levitt1,
Kathie
Eagleson1,
Sarah
Kennedy1, and
Ying
Wang1
1 Department of Neurobiology and Anatomy,
Allegheny University of the Health Sciences, Philadelphia, Pennsylvania
19129, and 2 The Wistar Institute of Anatomy and Biology,
Philadelphia, Pennsylvania 19104
A survival-promoting peptide has been purified from medium
conditioned by Y79 human retinoblastoma cells and a mouse hippocampal cell line (HN 33.1) exposed to H2O2. A 30 residue synthetic peptide was made on the basis of N-terminal sequences
obtained during purification, and it was found to exhibit gel mobility
and staining properties similar to the purified molecules. The peptide
maintains cells and their processes in vitro for the HN
33.1 cell line treated with H2O2, and
in vivo for cortical neurons after lesions of the cerebral cortex. It has weak homology with a fragment of a putative bacterial antigen and, like that molecule, binds IgG. The peptide also
contains a motif reminiscent of a critical sequence in the catalytic
region of calcineurin-type phosphatases; surprisingly, like several
members of this family, the peptide catalyzes the hydrolysis of
para-nitrophenylphosphate in the presence of
Mn2+. Application of the peptide to one side of
bilateral cerebral cortex lesions centered on area 2 in rats results in
an increase in IgG immunoreactivity in the vicinity of the lesions
7 d after surgery. Microglia immunopositive for IgG and
ED-1 are, however, dramatically reduced around the lesions in
the treated hemisphere. Furthermore, pyramidal neurons that would
normally shrink, die, or disintegrate were maintained, as determined by
MAP2 immunocytochemistry and Nissl staining. These survival effects
were often found in both hemispheres. The results suggest that this
peptide operates by diffusion to regulate the immune response and
thereby rescue neurons that would usually degenerate after cortical
lesions. The phosphatase activity of this molecule also suggests the
potential for direct neuron survival-promoting effects.
Key words:
peptide; neuron survival; immune evasion; microglia; IgG; phosphatase
Copyright © 1998 Society for Neuroscience 0270-6474/98/18187047-14$05.00/0
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