Superoxide scavenging effect of Ginkgo biloba extract on serotonin-induced mitogenesis.
We have reported previously that serotonin (5-HT) stimulates the mitogenesis of bovine pulmonary artery smooth muscle cells (SMCs) through active transport of 5-HT and cellular signaling that includes elevation of superoxide (O2.-) and enhancement of protein tyrosine phosphorylation. Ginkgo biloba extract 501 (EGb 501), which has been demonstrated to act as an antioxidant, was found to block both the elevated O2.- and the proliferative and hypertrophic influences of 5-HT on SMCs, but not to directly inhibit the associated activation of NAD(P)H oxidase or the stimulation of phosphorylation of GTPase-activating protein (GAP). A similar effect of Ginkgo biloba extract 501 occurred on Chinese hamster lung fibroblasts (CCL-39), where 5-HT receptor, as opposed to transporter, action has been associated with mitogenesis. We conclude from these studies that Ginkgo biloba extract 501 quenches O2.- formation by 5-HT, thereby blocking its mitogenic effect. Stimulation of protein tyrosine phosphorylation of GAP by 5-HT appears to precede the elevation of O2.-.
Lee
S L
SL
Department of Medicine, New England Medical Center/Tufts University School of Medicine, Boston, MA 02111, USA.
Wang
W W
WW
Lanzillo
J
J
Gillis
C N
CN
Fanburg
B L
BL
D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D005419:Flavonoids / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D020441:Ginkgo biloba; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D000096983:Ginkgo Extract
D005419:Flavonoids; D016166:Free Radical Scavengers; D010936:Plant Extracts; D012701:Serotonin; D012702:Serotonin Antagonists; D013481:Superoxides; D013936:Thymidine; D014443:Tyrosine; C114787:Ginkgo biloba extract 501; D000096983:Ginkgo Extract