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Platelet‐derived growth factor activates production of reactive oxygen species by NAD(P)H‐oxidase in smooth muscle cells through Gi1,2
Author(s) -
Kreuzer J.,
Viedt C.,
Brandes R. P.,
Seeger F.,
Rosenkranz A. S.,
Sauer H.,
Babich A.,
Nürnberg B.,
Kather H.,
KriegerBrauer H. I.
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-1036fje
Subject(s) - platelet derived growth factor receptor , gtpgammas , microbiology and biotechnology , growth factor , nadph oxidase , platelet derived growth factor , protein subunit , signal transduction , reactive oxygen species , biology , chemistry , biochemistry , receptor , g protein , gene
Recent findings indicate that platelet‐derived growth factor (PDGF) plays a role in the generation of reactive oxygen species (ROS) as second messengers in smooth muscle cells (SMC). To identify the source and signal transduction pathway of ROS formation in SMC, we investigated PDGF‐induced ROS formation. Stimulation of SMC with PDGF resulted in a rapid increase of ROS production. Using an inactivating antibody, we identified the increase to be dependent on p22phox, a NAD(P)H‐oxidase subunit. ROS release was completely inhibited by the Gi protein inhibitor PTX as well as an antibody against Gαi1,2, however, not by antibodies against Gαi3/0, Gαs, and Gβ1β2. The effect of PDGF on ROS production in SMC membranes could likewise be mimicked by the use of a recombinant Gαi2 subunit but not by Gαi3, Gαi0, Gαs, and Gβγ subunits. Immunoaffinity chromatography demonstrated coupling of Gαi1,2 to the PDGF α‐receptor, which, after preincubation of the SMC membranes with PDGF, was increased in the absence of GTPγS but decreased in the presence of GTPγS and prevented by PTX tretament. These data define a novel G protein‐dependent mechanism by which PDGF signaling is transduced through direct coupling of the Gαi1,2 subunit of the trimeric G proteins to the PDGF tyrosine kinase receptor.