title: Protein kinase-dependent effects of okadaic acid on hepatocytic autophagy and cytoskeletal integrity.
abstract: The protein phosphatase inhibitor okadaic acid suppressed autophagy completely in isolated rat hepatocytes, as measured by the sequestration of electroinjected [3H]raffinose into sedimentable autophagic vacuoles. Okadaic acid was effectively antagonized by the general protein kinase inhibitors K-252a and KT-5926, the calmodulin antagonist W-7, and by KN-62, a specific inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMK-II). These inhibitors also antagonized a cytoskeleton-disruptive effect of okadaic acid, manifested as the disintegration of cell corpses after breakage of the plasma membrane. CaMK-II, or a closely related enzyme, would thus seem to play a role in the control of autophagy as well as in the control of cytoskeletal organization.
authors.affiliation: Department of Tissue Culture, Norwegian Radium Hospital, Oslo.
authors.forename: I
authors.initials: I
authors.lastname: Holen
authors.forename: P B
authors.initials: PB
authors.lastname: Gordon
authors.forename: P O
authors.initials: PO
authors.lastname: Seglen
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives*; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D026121:Indole Alkaloids; D007211:Indoles; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D011887:Raffinose / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013449:Sulfonamides / Q000494:pharmacology; D014316:Tritium
chemical_list: D000470:Alkaloids; D002147:Calmodulin; D002227:Carbazoles; D004988:Ethers, Cyclic; D026121:Indole Alkaloids; D007211:Indoles; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D014316:Tritium; C063769:KT 5926; D019319:Okadaic Acid; C063302:KN 62; C017967:W 7; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C049985:staurosporine aglycone; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases; D011887:Raffinose