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PMID: 1320371 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Protein kinase-dependent effects of okadaic acid on hepatocytic autophagy and cytoskeletal integrity.

The Biochemical journal ·Vol. 284 ( Pt 3) ·1992-06-15 ·Pages 633-6

Holen I, Gordon PB, Seglen PO

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.

MeSH Terms
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives Alkaloids/pharmacology Animals Autophagy/drug effects Calcium-Calmodulin-Dependent Protein Kinases Calmodulin/antagonists & inhibitors Carbazoles/pharmacology Cells, Cultured Cytoskeleton/drug effects,ultrastructure Ethers, Cyclic/pharmacology Indole Alkaloids Indoles Isoquinolines/pharmacology Kinetics Liver/drug effects,physiology,ultrastructure Male Okadaic Acid Phosphoprotein Phosphatases/antagonists & inhibitors Piperazines/pharmacology Protein Kinase Inhibitors Protein Kinases/metabolism Raffinose/metabolism Rats Rats, Inbred Strains Sulfonamides/pharmacology Tritium
Chemicals
Alkaloids Calmodulin Carbazoles Ethers, Cyclic Indole Alkaloids Indoles Isoquinolines Piperazines Protein Kinase Inhibitors Sulfonamides Tritium KT 5926 Okadaic Acid KN 62 W 7 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine staurosporine aglycone Protein Kinases Calcium-Calmodulin-Dependent Protein Kinases Phosphoprotein Phosphatases Raffinose
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Holen I
Department of Tissue Culture, Norwegian Radium Hospital, Oslo.
Gordon P B
Seglen P O
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj2840633
Published
1992-06-15
Pages
633-6
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1132582
Subset
IM
External Links
PubMed source DOI: 10.1042/bj2840633 PMC Full Text View journal details
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