Downstream components of RhoA required for signal pathway of superoxide formation during phagocytosis of serum opsonized zymosans in macrophages.
- Author:
Jun Sub KIM
1
;
Jae Gyu KIM
;
Chan Young JEON
;
Ha Young WON
;
Mi Young MOON
;
Ji Yeon SEO
;
Jong Il KIM
;
Jaebong KIM
;
Jae Yong LEE
;
Soo Young CHOI
;
Jinseu PARK
;
Jung Han YOON PARK
;
Kwon Soo HA
;
Pyeung Hyeun KIM
;
Jae Bong PARK
Author Information
1. Department of Biochemistry, College of Medicine, Hallym University, Chuncheon 220-702, Korea. jbpark@hallym.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
extracellular signal-regulated MAP kinases;
macrophages;
NADPH oxidase;
P38 mitogen-activated protein kinases;
rhoA GTP-binding protein;
superoxides
- MeSH:
Animals;
Cell Line;
Cell Membrane;
Cytosol;
Enzyme Inhibitors/pharmacology;
Extracellular Signal-Regulated MAP Kinases/metabolism;
Macrophage-1 Antigen/pharmacology;
Macrophages/drug effects/*metabolism/ultrastructure;
Mice;
Myosin-Light-Chain Kinase/metabolism;
Opsonin Proteins/blood/*metabolism;
*Phagocytosis;
Protein Transport;
Protein-Serine-Threonine Kinases/metabolism;
Research Support, Non-U.S. Gov't;
*Signal Transduction;
Superoxides/*metabolism;
Tetradecanoylphorbol Acetate/pharmacology;
Zymosan/*blood;
p38 Mitogen-Activated Protein Kinases/metabolism;
rhoA GTP-Binding Protein/antagonists & inhibitors/*metabolism
- From:Experimental & Molecular Medicine
2005;37(6):575-587
- CountryRepublic of Korea
- Language:English
-
Abstract:
Rac1 and Rac2 are essential for the control of oxidative burst catalyzed by NADPH oxidase. It was also documented that Rho is associated with the superoxide burst reaction during phagocytosis of serum- (SOZ) and IgG-opsonized zymosan particles (IOZ). In this study, we attempted to reveal the signal pathway components in the superoxide formation regulated by Rho GTPase. Tat-C3 blocked superoxide production, suggesting that RhoA is essentially involved in superoxide formation during phagocytosis of SOZ. Conversely SOZ activated both RhoA and Rac1/2. Inhibition of RhoA-activated kinase (ROCK), an important downstream effector of RhoA, by Y27632 and myosin light chain kinase (MLCK) by ML-7 abrogated superoxide production by SOZ. Extracellular signaling-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) were activated during phagocytosis of SOZ, and Tat-C3 and SB203580 reduced ERK1/2 and p38 MAPK activation, suggesting that RhoA and p38 MAPK may be upstream regulators of ERK1/2. Inhibition of ERK1/2, p38 MAPK, phosphatidyl inositol 3-kinase did not block translocation of RhoA to membranes, suggesting that RhoA is upstream to these kinases. Inhibition of RhoA by Tat-C3 blocked phosphorylation of p47 PHOX. Taken together, RhoA, ROCK, p38MAPK, ERK1/2, and p47 PHOX may be subsequently activated, leading to activation of NADPH oxidase to produce superoxide.
