raffinose and staurosporine-aglycone

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.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Alkaloids; Animals; Autophagy; Calcium-Calmodulin-Dependent Protein Kinases; Calmodulin; Carbazoles; Cells, Cultured; Cytoskeleton; Ethers, Cyclic; Indole Alkaloids; Indoles; Isoquinolines; Kinetics; Liver; Male; Okadaic Acid; Phosphoprotein Phosphatases; Piperazines; Protein Kinase Inhibitors; Protein Kinases; Raffinose; Rats; Rats, Inbred Strains; Sulfonamides; Tritium