Downstream components of RhoA required for signal pathway of superoxide formation during phagocytosis of serum opsonized zymosans in macrophages

• Published in: Experimental & molecular medicine 2005, 37(6), , pp.575-587
• Main Authors: 김준섭, 김재규, 전찬영, 원하영, 문미영, 서지연, 김종일, 김재봉, 이재용, 최수영, 박진서, 윤정한, 하권수, 김평현, 박재봉
• Format: Article
• Language: Korean
• Subjects: 생화학
• ISSN: 1226-3613; 2092-6413

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 sig-naling-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 phatidyl 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 p47PHOX. Taken together, RhoA, ROCK, p38MAPK, ERK1/2, and p47PHOX may be subsequently activated, leading to activation of NADPH oxidase to produce superoxide. KCI Citation Count: 26