Brefeldin A inhibits the targeting of cathepsin D and cathepsin H to lysosomes in rat hepatocytes.
Effect of brefeldin A on the transport of lysosomal acid hydrolases (cathepsins D and H) was investigated in primary cultured rat hepatocytes. Both cathepsins were synthesized as proenzymes and progressively converted to mature enzymes in the control cells. However, BFA strongly inhibited the appearance of the mature enzymes in the cells in a dose dependent manner, suggesting that transport of newly synthesized lysosomal enzymes from the endoplasmic reticulum to lysosomes is blocked by the drug. The inhibitory effect by brefeldin A was reversible. Upon recovery from brefeldin A-intoxication, procathepsin D was effectively targeted into lysosomes, whereas a substantial amount of procathepsin H was found to be missorted, resulting in its secretion into the culture medium.
Department of Biochemistry, Fukuoka University School of Medicine, Japan.
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Oda
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Nishimura
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D020126:Brefeldin A; D002402:Cathepsin D / Q000378:metabolism*; D056655:Cathepsin H; D002403:Cathepsins / Q000378:metabolism*; D002451:Cell Compartmentation / Q000187:drug effects*; D002478:Cells, Cultured; D003517:Cyclopentanes / Q000494:pharmacology*; D003546:Cysteine Endopeptidases; D006056:Golgi Apparatus / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008247:Lysosomes / Q000201:enzymology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051381:Rats
D003517:Cyclopentanes; D020126:Brefeldin A; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D056655:Cathepsin H; C534128:Ctsh protein, rat; D002402:Cathepsin D