Citation:
L. Shanshiashvili, B. Pichkhadze, G. Machaidze, J.J. Ramsden, D. Mikeladze; Myelin basic protein peptide 45–89 induces the release of nitric oxide from microglial cells. Journal of Biological Physics and Chemistry Vol 2 No 1/2, 2002 pp7–11
Abstract:
Continuous (24 h) exposure of mixed oligodendrocyte/microglial cells to peptides
45–89 derived from citrullinated C8 isoforms of myelin basic protein (MBP) induces
cell death. In contrast, MBP-C8 at the same molecular concentration is not
toxic to oligodendrocyte/microglial cells as detected by the MTT test and trypan
blue exclusion method. The loss of oligodendrocyte/microglial cells resulted in the
release of cytochrome c from mitochondria, suggesting MBP 45–89-induced
apoptosis. On the other hand, peptides 45–89 stimulated the secretion of nitric
oxide from microglial cells only via induction of iNOS. The addition of peptide
45–89 to the microglial cells led to a decrease of the level of the inhibitory protein
IkB, indicating that activation of the transcription factor NF-kB is involved in these
processes. We propose that the immunodominant peptide 45–89 induces damage of
oligodendrocytes by activation of microglial cells and subsequent generation of
nitric oxide, and that this may be the first step in the initiation of autoimmunity.