Altered spectrum of retrogradely transported axonal proteins in p-bromophenylacetylurea neuropathy

The composition of retrogradely transported axonal proteins was examined by acrylamide gel electrophoresis and gel autoradiography in the experimental neuropathy induced in rats by p-bromophenylacetylurea (BPAU). Protein composition was normal during the early phase of retrograde transport but showed significant abnormalities during a later phase. The early phase consisted of proteins collected distal to a mid-thigh ligature of sciatic nerve between 15 and 24 hours after injection of [35S] methionine into lumbar ventral horn of the spinal cord. In terms of their relative labeling and electrophoretic mobility, these proteins were almost identical in experimental and control rats. Most of the labeled protein bands were also identical in the later phase, collected between 24 and 48 hours, but there were some consistent omissions and additions. Present in controls but missing in BPAU treated rats were three bands at 42, 41, and 25 KDa. In contrast, 4 bands (63, 56, 50, 26 KDa) were more prominent in the experimental rats than in controls. We suspect abnormal post-translational modification or proteolysis of rapidly transported proteins in the terminal or preterminal portion of the neurons exposed to BPAU. This abnormality, in addition to a previously reported premature processing of transported organelles, may underlie the development of peripheral neuropathy.