Exp Mol Med.
2005 Dec;37(6):575-587.
Downstream components of RhoA required for signal pathway of superoxide formation during phagocytosis of serum opsonized zymosans in macrophages
- Affiliations
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- 1Department of Biochemistry, College of Medicine, Hallym University, Chuncheon 220-702, Korea. jbpark@hallym.ac.kr
- 2Department of Genetic Engineering, Hallym University, Chuncheon 220-702, Korea.
- 3Department of Nutrition, Division of Life Science, Hallym University, Chuncheon 220-702, Korea.
- 4Department of Biochemistry, Kangwon National University, Chuncheon 200-701, Korea.
- 5Department of Microbiology, College of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
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.
Keyword
MeSH Terms
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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
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