Lesion-induced synthesis and secretion of proteins by nonneuronal cells resident in frog peripheral nerve.

Transection of a peripheral nerve results in Wallerian degeneration of the nerve segment distal to the lesion site and the initiation of axonal regeneration just proximal to it (neuroma site). Nonneuronal cells resident in peripheral nerve are suggested to play an important role in neural repair mechanisms through diffusable molecules that they synthesize and secrete. We examined the array of proteins synthesized and secreted by nonneuronal cells resident in the frog peripheral nerve, which is known for its high regenerative capacity. Nerve segments were incubated in medium containing [35S]methionine, and the secreted radioactively labeled proteins were analyzed by gel electrophoresis. Nerve injury resulted in the complete down-regulation of a group of proteins synthesized and secreted by nonneuronal cells in intact nerve. At the same time, the synthesis and secretion of several proteins were up-regulated in the neuroma and degenerating nerve segments, proximal and distal to the axotomy site, respectively. Proteins secreted by the proximal segment were of apparent kDa/pI (mass/isoelectric point) values of 215/5.6, 76/6.7, 73/7.0, 44/5.2, 36.5/5.6, 35.5/6.0, and 32/6.0. Similar proteins were secreted by the degenerating distal segment but with the exception of variable reductions in the 44- and 32-kDa proteins and increases in proteins of apparent kDa/pI values of 39/5.2 and 29/7.3-7.4. Step gradient ultracentrifugation suggested that the latter two are apolipoproteins. Comparison with plasma apolipoproteins further indicated that nerve and plasma apolipoproteins differ. The up-regulation of the synthesis and secretion of these proteins concurrently with nerve degeneration and regeneration strongly imply that these molecules are involved in neuronal repair mechanisms.