Vinblastine inhibits the maturation of the precursor of mitochondrial aspartate aminotransferase. Vincristine and six other cytoskeleton inhibitors do not show this effect.
Cytoskeleton inhibitors were tested in chicken embryo fibroblast cultures for possible effects on the import of the precursor of mitochondrial aspartate aminotransferase into mitochondria. Vinblastine (50 microM) increased the steady-state pool of the precursor 2.5-fold in pulse experiments with [35S]methionine. If the precursor was accumulated during a pulse in the presence of the uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) and then chased under diluting CCCP, vinblastine (50 microM) prolonged the half-life of the precursor from 0.5 min in the control to 3 min. Other cytoskeleton inhibitors, i.e. vincristine (25 to 150 microM), colchicine (50 microM), nocodazole (50 microM), podophyllotoxin (50 microM), taxol (45 microM), cytochalasin D (20 microM) and phalloidin (25 microM) did not show this effect. The observed inhibition by vinblastine does not seem to relate to its action on microtubuli.
D000470:Alkaloids / Q000633:toxicity; D000818:Animals; D001219:Aspartate Aminotransferases / Q000235:genetics*; D001562:Benzimidazoles / Q000494:pharmacology; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002478:Cells, Cultured; D002642:Chick Embryo; D003078:Colchicine / Q000494:pharmacology; D015638:Cytochalasin D; D003572:Cytochalasins / Q000494:pharmacology; D004792:Enzyme Precursors / Q000235:genetics*; D005347:Fibroblasts / Q000201:enzymology; D007700:Kinetics; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D015739:Nocodazole; D010101:Oxygen Consumption / Q000187:drug effects; D017239:Paclitaxel; D010590:Phalloidine / Q000494:pharmacology; D011034:Podophyllotoxin / Q000494:pharmacology; D014747:Vinblastine / Q000494:pharmacology*
D000470:Alkaloids; D001562:Benzimidazoles; D003572:Cytochalasins; D004792:Enzyme Precursors; D010590:Phalloidine; D015638:Cytochalasin D; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D014747:Vinblastine; D001219:Aspartate Aminotransferases; D011034:Podophyllotoxin; D017239:Paclitaxel; D015739:Nocodazole; D003078:Colchicine