Effect of experimental colchicine encephalopathy on brain protein synthesis and tubulin metabolism.
Colchicine blocks axoplasmic flow and produces neurofibrillary degeneration. Brain slices from mice injected intracerebrally with colchicine incorporated more [14C]leucine into protein and had a decreased uptake of [14C]leucine into the perchloric acid-soluble pool than did their controls. Brain RNA content was decreased and free leucine increased by colchicine-induced encephalopathy. The specific activities of proteins from subcellular fractions of colchicine-injected brain were increased in the nuclear fraction, the 100,000-g supernatant, and its vinblastine-precipitable tubulin. The ratio of the specific activity of the crude mitochondrial fraction to that of the total homogenate was decreased, as would be consistent with impaired movement of newly labeled protein into synaptosomes. Colchicine-injected brain extracts contained one or more cytosol fractions that stimulated ribosomal incorporation of [14C]leucine into protein in a cell-free system. Colchicine-binding-activity measurements indicated loss of soluble and particulate tubulin in colchicine-injected brains; the decrease of soluble tubulin was verified by its selective precipitation with vinblastine. Colchicine encephalopathy did not affect the rate of spontaneous breakdown of in vitro colchicine binding activity. Similarities of colchicine encephalopathy to the neuron's response to axonal damage suggest that colchicine-induced increase in protein synthesis may, in part, reflect a neuronal response to blockage of neuroplasmic transport.
D000818:Animals; D001370:Axonal Transport / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002458:Cell Fractionation; D003078:Colchicine / Q000378:metabolism / Q000494:pharmacology*; D006023:Glycoproteins / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism; D051379:Mice; D008861:Microsomes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism*
D006023:Glycoproteins; D009419:Nerve Tissue Proteins; D012269:Ribosomal Proteins; D014404:Tubulin; D012313:RNA; D007930:Leucine; D003078:Colchicine