ROLES OF HIPPOCAMPAL CHOLINERGIC NEUROSTIMULATING PEPTIDE PRECURSOR PROTEIN (HCNP-PP) IN SKELETAL MUSCLE REGENERATION AND L6-CELL DIFFERENTIATION

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Hippocampal cholinergic neurostimulating peptide (HCNP), originally purified from young rat hippocampus, enhances phenotype development among septo-hippocampal cholinergic neurons in vitro. The precursor protein of HCNP (HCNP-pp) has been shown to be multifunctional, acting not only as a precursor of HCNP, but also as a protein binding phosphatidylethanolamine and ATP. Further, the precursor protein (as phosphatidylethanolamine-binding protein) has been suggested to inhibit the mitogen-activated protein kinase (MAPK) cascade. Previously, having demonstrated that HCNP-pp specifically accumulates in skeletal muscles in inclusion-body myositis, we suggested that it is involved in the pathogenesis of this disorder. To ascertain whether HCNP-pp really is involved in skeletal muscle development, we focused on the expression of HCNP-pp and on the MAPK cascade during muscle regeneration following traumatic injury and during the development of L6 myoblast cells. Although there were discrepancies between our two analytic modalities (immunocytochemistry and Western blot analysis) HCNP-pp expression and the activity of the MAPK cascade were not correlated, they behaved independently, during skeletal muscle regeneration. This was substantiated by a study of L6-cell maturation, and although transfection of the cells with an HCNP-pp cDNA adenoviral vector increased HCNP-pp expression, the activity of extracellular signal-regulated kinase (which is downstream of the MAPK cascade) was not inhibited. These results suggest that during skeletal muscle development and regeneration, component (s) other than HCNP-pp are involved in the regulation of the MAPK cascade.

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