Calyculin A modulates activation of the NADPH-oxidase in Me2SO-differentiated HL-60 cells.
- Author:
Joo In PARK
1
;
David J UHLINGER
;
Byeung Seon CHUNG
;
In Hoo KIM
;
Jong Young KWAK
Author Information
1. Department of Biochemistry, Dong-A University College of Medicine, Pusan, Korea. jipark@seunghak.donga.ac.kr
- Publication Type:Original Article
- Keywords:
NADPH-oxidase;
calyculin A;
p47-phox;
p67-phox;
arachidonic acid
- MeSH:
Arachidonic Acid/metabolism;
Ca(2+)-Calmodulin Dependent Protein Kinase/metabolism;
Cell Differentiation;
Dimethyl Sulfoxide/pharmacology*;
Enzyme Inhibitors/pharmacology*;
HL-60 Cells;
Human;
N-Formylmethionine Leucyl-Phenylalanine/pharmacology;
NADPH Oxidase/metabolism*;
Neutrophils/metabolism*;
Neutrophils/drug effects;
Oxazoles/pharmacology*;
Oxygen/metabolism;
Phosphoprotein Phosphatase/antagonists & inhibitors;
Phosphoproteins/immunology;
Signal Transduction;
Tetradecanoylphorbol Acetate/pharmacology;
Time Factors
- From:Experimental & Molecular Medicine
1998;30(4):214-220
- CountryRepublic of Korea
- Language:English
-
Abstract:
Human promyelocytic leukemia cells (HL-60) have been used as a model system in which to study the effects of protein phosphatase inhibitors on NADPH-oxidase activation. Since O2- is generated by NADPH-oxidase, we examined the effect of calyculin A pretreatment on oxidase activation in response to various agonists. When Me2SO-differentiated HL-60 cells were treated with calyculin A prior to the addition of phorbol 12-myristate 13-acetate (PMA), O2- production was inhibited; however, calyculin A enhanced O2- production by N-formyl-methionyl-leucyl-phenylalanine (FMLP). The decreased O2- production seen with calyculin A pretreatment followed by PMA may be due to diminished translocation of the p47-phox and p67-phox, cytosolic components of the oxidase, and inhibition of arachidonic acid release. Interestingly calyculin A pretreatment followed by either agonist significantly enhanced mitogen-activated-protein kinase (MAPK) activity. The differential effects of pretreatment with calyculin A on subsequent oxidase stimulation elicited by FMLP or PMA provide further evidence for substantial heterogeneity in the activation of the respiratory burst.
