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Confocal Imaging of Single Mitochondrial Superoxide Flashes in Intact Heart or In Vivo
Published on: November 6, 2013
Superoxide as an intermediate signal for serotonin-induced mitogenesis
S L Lee1, W W Wang, B L Fanburg
1Pulmonary and Critical Care Division/Department of Medicine/Tupper Research Institute/New England Medical Center/Tufts University School of Medicine, Boston, MA 02111, USA.
Free Radical Biology & Medicine
|May 20, 1998
Summary
Serotonin (5-HT) triggers smooth muscle cell proliferation by increasing oxygen radical (O2.-) formation via its transport system. Inhibiting this pathway blocks proliferation, suggesting a novel therapeutic target for vascular diseases.
Area of Science:
- Cell Biology
- Biochemistry
- Vascular Physiology
Background:
- Serotonin (5-HT) is known to stimulate tyrosine phosphorylation and proliferation in bovine pulmonary artery smooth muscle cells (SMC).
- The precise signaling mechanisms underlying 5-HT-induced SMC proliferation require further elucidation.
Purpose of the Study:
- To investigate the role of oxygen radical (O2.-) formation and 5-HT transport in 5-HT-induced SMC proliferation.
- To identify key molecular players in the 5-HT signaling pathway.
Main Methods:
- Lucigenin-enhanced chemiluminescence assay to measure O2.- formation.
- Utilized inhibitors of 5-HT transport (imipramine), NAD(P)H oxidase (diphenyliodonium), glutathione (N-acetyl-cysteine), O2.- scavenging (Tiron), and p21ras (alpha-hydroxyfarnesylphosphonic acid).
- Compared responses in SMC and endothelial cells.
Main Results:
- 5-HT rapidly elevated O2.- formation in SMC within 10 minutes.
- Tiron and N-acetyl-cysteine blocked both 5-HT-induced O2.- formation and proliferation.
- Imipramine and diphenyliodonium inhibited both 5-HT-induced O2.- elevation and proliferation.
- Alpha-hydroxyfarnesylphosphonic acid inhibited 5-HT-induced proliferation.
- Endothelial cells did not exhibit 5-HT-induced proliferation or O2.- formation.
Conclusions:
- 5-HT induces SMC proliferation through signaling pathways involving its transport system and O2.- formation.
- NAD(P)H oxidase and p21ras are critical components of this signaling cascade.
- These findings highlight a potential therapeutic target for vascular proliferation disorders.
