Neurochemical Research, VoL 18, No. 6, 1993, pp. 675-680 Altered Spectrum of Retrogradely Transported Axonal Proteins in p-Bromophenylacetylurea Neuropathy Nobuyuki Oka I and Stephen Brimijoin 2 (Accepted October 19, 1992) 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 ret- rograde transport but showed significant abnormalities during a later phase. The early phase con- sisted of proteins collected distal to a mid-thigh ligature of sciatic nerve between 15 and 24 hours after injection of [3sS] 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 devel- opment of peripheral neuropathy. KEY WORDS: p-Bromophenylacetylurea; neuropathy;a• protein; retrogradetransport; rat nerve. INTRODUCTION It has been hypothesized that disturbances of the turnaround and rapid retrograde axonal transport of pro- teins and organelles underlie several of the experimental neuropathies induced by chemical agents such as p- bromophenylacetylurea (BPAU), zinc pyrithione, and acrylamide (1-4). BPAU-induced neuropathy involves a dramatic accumulation of tubulomembranous materials in distal and preterminal axons (5,6). A study in our laboratory on the axonal transport of newly synthesized proteins in rat sciatic nerve showed a marked decrease 1 Departmentof Neurology,KyotoUniversity,Sakyo-ku,Kyoto606 Japan. 2 Departmentof Pharmacology, MayoClinic, Rochester,Minnesota, 55905. of retrograde transport, 24 hours after radiolabelling in spinal cord (7). This finding led us to suspect that BPAU induces local stasis of rapidly transported materials that would normally be returned to neuronal perikarya by retrograde transport. We recently used electron micro- scope autoradiography to demonstrate that the organelles that accumulate in BPAU neuropathy are probably de- posited in the distal axon soon after arrival by fast an- terograde axonal transport (8). At present, there is no information to explain why this kind of local stasis should occur. The current study was designed to shed light on this issue by examining in more detail the nature of the proteins undergoing rapid anterograde and retrograde transport in sciatic nerves after treatment with BPAU. 675 0364-3190/93/0600-0675507,00/0 9 1993 Plenum Publishing Corporation