Serotonin stimulates mitogen-activated protein kinase activity through the formation of superoxide anion.

@article{Lee1999SerotoninSM,
  title={Serotonin stimulates mitogen-activated protein kinase activity through the formation of superoxide anion.},
  author={Sheu-Ling Janet Lee and Wei-wei Wang and Geraldine A. Finlay and Barry L Fanburg},
  journal={American journal of physiology. Lung cellular and molecular physiology},
  year={1999},
  volume={277 2},
  pages={L282-L291}
}
  • S. LeeWei-wei Wang B. Fanburg
  • Published 1 August 1999
  • Biology
  • American journal of physiology. Lung cellular and molecular physiology
Our previous studies have shown that, through an active transport process, serotonin (5-HT) rapidly elevates[Formula: see text] formation, stimulates protein phosphorylation, and enhances proliferation of bovine pulmonary artery smooth muscle cells (SMCs). We presently show that 1 μM 5-HT also rapidly elevates phosphorylation and activation of the mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase (ERK) 1 and ERK2 of SMCs, and the enhanced phosphorylation is blocked… 

Phospholipase D signaling in serotonin-induced mitogenesis of pulmonary artery smooth muscle cells.

  • Y. LiuB. Fanburg
  • Biology, Chemistry
    American journal of physiology. Lung cellular and molecular physiology
  • 2008
Results indicate that ligation of the 5-HTR 2A by 5-HT initiates PLD activation in SMCs, and that its product, PA, is an early signaling molecule in 5- HT-induced pulmonary artery SMC proliferation.

Rho Kinase–Induced Nuclear Translocation of ERK1/ERK2 in Smooth Muscle Cell Mitogenesis Caused by Serotonin

The studies show for the first time to the knowledge combinational action of SERT and a 5-HT receptor in SMC growth and Rho A/ROCK participation in 5- HT receptor 1B/1D-mediated mitogenesis of vascular SMCs through an effect on cytoplasmic to nuclear translocation of ERK1/ERK2.

5-HT Induction of c-fos gene expression requires reactive oxygen species and rac1 and ras GTPases

It is shown by Western blot that 5-HT upregulates c-Fos, an immediate early gene product known to regulate the entrance of quiescent cells into the cell cycle, and Regulation of cyclin D1, a protein shown to be regulated by c-fos and required for entry into thecell cycle, is upregulated by 5- HT and is blocked by DPI and PD98059.

Activation of Erk Mitogen-Activated Protein Kinase Proteins by Vascular Serotonin Receptors

While mRNA and possibly protein for multiple 5-HT receptors are present in aortic smooth muscle, only the 5- HT 2A receptor plays a significant role in directly modulating contractility and activating the Erk MAPK pathway.

H(2)O(2) signals 5-HT-induced ERK MAP kinase activation and mitogenesis of smooth muscle cells.

Generation of O(2)(-) in BPASMCs in response to 5-HT is followed by an increase in intracellular H( 2)O(2) that mediates 5- HT-induced mitogenesis through activation of ERK1/ERK2 but not of p38 MAP kinase.

Inhibition of serotonin-induced mitogenesis, migration, and ERK MAPK nuclear translocation in vascular smooth muscle cells by atorvastatin.

It is suggested that atorvastatin inhibits 5-HT-induced PASM cell mitogenesis and migration through targeting isoprenylation which may, in part, attenuate the Rho pathway, a mechanism that may apply to statin effects on in vivo models of pulmonary hypertension.

JNK regulates serotonin-mediated proliferation and migration of pulmonary artery smooth muscle cells.

It is demonstrated that JNK activity is necessary for serotonin (5-HT)-induced proliferation and migration of bovine pulmonary artery smooth muscle cells (PASMCs) and may act at an important point for cross talk of the MAPK and PI3K pathways.

A new hypertrophic mechanism of serotonin in cardiac myocytes: receptor‐independent ROS generation

The data suggest that part of cardiac hypertrophic effect of serotonin requires hydrogen peroxide production by MAO A and ERK1/2 activation, and this newly recognized, receptor‐independent mechanism of serotonin may contribute to myocardial remodeling and failure.

Serotonin activation of the ERK pathway in Hermissenda: contribution of calcium‐dependent protein kinase C

Results indicate that Ca2+‐dependent PKC activation contributes to ERK phosphorylation, although a PKC‐independent pathway is also involved in 5‐HT‐dependent ERKosphorylation and activation.

Signaling Pathways Linked to Serotonin-Induced Superoxide Anion Production: A Physiological Role for Mitochondria in Pulmonary Arteries

In physiological conditions,5-HT acts on 5-HT2 receptors and induces an O2•_ production dependent on extracellular calcium and mitochondria, which is transiently depolarized the mitochondrial membrane whereas in the absence of extrace cellular calcium the mitochondrial membranes depolarisation was delayed and sustained in response to 5- HT.
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References

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Association of Tyr phosphorylation of GTPase-activating protein with mitogenic action of serotonin.

The present studies demonstrate rapid enhancement by 5-HT of Tyr phosphorylation of proteins, including p120, which also occurs in SMC but not in EC, and indicate that Tyr phosphORYlation of GAP may act as an intermediate signal in5-HT-induced mitogenesis of SMC which requires cellular internalization of 5- HT rather than its action on a membrane receptor.

Superoxide as an intermediate signal for serotonin-induced mitogenesis.

Histamine Antagonizes Serotonin and Growth Factor-induced Mitogen-activated Protein Kinase Activation in Bovine Tracheal Smooth Muscle Cells (*)

The data suggest a model whereby 5-HT activates MAP kinase via a protein kinase C/Raf-1 pathway, and histamine attenuatesMAP kinase activation by serotonin via activation of cAMP-dependentprotein kinase A and inhibition of Raf-1.

Ras Involvement in Signal Transduction by the Serotonin 5-HT2B Receptor (*)

It is shown that agonist stimulation of the 5-HT2B receptor subtype stably expressed in the mouse fibroblast LMTK cell line causes a rapid and transient activation of the proto-oncogene product p21 as measured by an increase in GTP-bound Ras in response to serotonin.

Serotonin activates the mitogen-activated protein kinase pathway in vascular smooth muscle: use of the mitogen-activated protein kinase kinase inhibitor PD098059.

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  • Biology, Chemistry
    The Journal of pharmacology and experimental therapeutics
  • 1996
The findings suggest that 5-HT-induced activation of tyrosine kinase(s) may be a signal transduction pathway used by vascular5-HT2A receptors and the use of the mitogen-activated protein kinase pathway by 5- HT in causing arterial contraction is supported.

Integration of mitogen-activated protein kinase kinase activation in vascular 5-hydroxytryptamine2A receptor signal transduction.

  • J. FlorianS. Watts
  • Biology, Chemistry
    The Journal of pharmacology and experimental therapeutics
  • 1998
Vascular 5-Hydroxytryptamine2A (5-HT2A) receptor signaling and contraction has been associated with the activation of L-type calcium channels, phospholipase C (PLC) and, as we previously

Activation of the Mitogen-activated Protein Kinase Signaling Pathway in Neutrophils

It is concluded that oxidant treatment of neutrophils can activate mitogen-activated protein (MAP) kinase by stimulating its tyrosine and (presumably) threonine.

Hydrogen peroxide stimulates mitogen-activated protein kinase in bovine tracheal myocytes: implications for human airway disease.

The effects of hydrogen peroxide (H2O2) on mitogen-activated protein (MAP) kinase activation in bovine tracheal myocytes were assessed, demonstrating that H2O1 can stimulate the tyrosine phosphorylation of multiple cytosolic proteins, including MAP kinase.
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