5-Hydroxytryptamine(1A) receptor/G(i)βγ stimulates mitogen-activated protein kinase via NAD(P)H oxidase and reactive oxygen species upstream of Src in Chinese hamster ovary fibroblasts

Yurii V. Mukhin, Maria N. Garnovskaya, Georgiann Collinsworth, Jasjit S. Grewal, DeKisha Pendergrass, Toshio Nagai, Stephen Pinckney, Eddie L. Greene, John R. Raymond

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

The hypothesis of this work is that the 'serotonin' or 5-hydroxytryptamine (5-HT)(1A) receptor, which activates the extracellular signal-regulated kinase (ERK) through a G(i)βγ-mediated pathway, does so through the intermediate actions of reactive oxygen species (ROS). Five criteria were shown to support a key role for ROS in the activation of ERK by the 5-HT(1A) receptor. (1) Antioxidants inhibit activation of ERK by 5-HT. (2) Application of cysteine-reactive oxidant molecules activates ERK. (3) The 5-HT(1A) receptor alters cellular redox properties, and generates both superoxide and hydrogen peroxide. (4) A specific ROS-producing enzyme [NAD(P)H oxidase] is involved in the activation of ERK. (5) There is specificity both in the effects of various chemical oxidizers, and in the putative location of the ROS in the ERK activation pathway. We propose that NAD(P)H oxidase is located in the ERK activation pathway stimulated by the transfected 5-MT(1A) receptor in Chinese hamster ovary (CHO) cells downstream of G(i)βγ subunits and upstream of or at the level of the non-receptor tyrosine kinase, Src. Moreover, these experiments provide confirmation that the transfected human 5-HT(1A) receptor induces the production of ROS (superoxide and hydrogen peroxide) in CHO cells, and support the possibility that an NAD(P)H oxidase-like enzyme might be involved in the 5-HT-mediated generation of both superoxide and hydrogen peroxide.

Original languageEnglish (US)
Pages (from-to)61-67
Number of pages7
JournalBiochemical Journal
Volume347
Issue number1
DOIs
StatePublished - Apr 1 2000
Externally publishedYes

Fingerprint

Receptor, Serotonin, 5-HT1A
NADPH Oxidase
Extracellular Signal-Regulated MAP Kinases
Fibroblasts
Cricetulus
Mitogen-Activated Protein Kinases
Ovary
Reactive Oxygen Species
Chemical activation
Mitogen-Activated Protein Kinase 7
Superoxides
Hydrogen Peroxide
Serotonin
Gastrin-Secreting Cells
Enzymes
Oxidants
Protein-Tyrosine Kinases
Oxidation-Reduction
Cysteine
Antioxidants

Keywords

  • G protein
  • Phosphorylation
  • Proliferation
  • Serotonin receptor
  • Tyrosine kinase

ASJC Scopus subject areas

  • Biochemistry

Cite this

5-Hydroxytryptamine(1A) receptor/G(i)βγ stimulates mitogen-activated protein kinase via NAD(P)H oxidase and reactive oxygen species upstream of Src in Chinese hamster ovary fibroblasts. / Mukhin, Yurii V.; Garnovskaya, Maria N.; Collinsworth, Georgiann; Grewal, Jasjit S.; Pendergrass, DeKisha; Nagai, Toshio; Pinckney, Stephen; Greene, Eddie L.; Raymond, John R.

In: Biochemical Journal, Vol. 347, No. 1, 01.04.2000, p. 61-67.

Research output: Contribution to journalArticle

Mukhin, Yurii V. ; Garnovskaya, Maria N. ; Collinsworth, Georgiann ; Grewal, Jasjit S. ; Pendergrass, DeKisha ; Nagai, Toshio ; Pinckney, Stephen ; Greene, Eddie L. ; Raymond, John R. / 5-Hydroxytryptamine(1A) receptor/G(i)βγ stimulates mitogen-activated protein kinase via NAD(P)H oxidase and reactive oxygen species upstream of Src in Chinese hamster ovary fibroblasts. In: Biochemical Journal. 2000 ; Vol. 347, No. 1. pp. 61-67.
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AU - Mukhin, Yurii V.

AU - Garnovskaya, Maria N.

AU - Collinsworth, Georgiann

AU - Grewal, Jasjit S.

AU - Pendergrass, DeKisha

AU - Nagai, Toshio

AU - Pinckney, Stephen

AU - Greene, Eddie L.

AU - Raymond, John R.

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KW - Phosphorylation

KW - Proliferation

KW - Serotonin receptor

KW - Tyrosine kinase

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