Reciprocal regulation of ATPγS-induced monocyte chemoattractant protein-1 production by ERK and p38 MAP kinasesin rat corticostriatal slice cultures

Takahiro Katayama, Misato Ito, Shuji Kaneko, Masamichi Satoh, Takashi Uehara, Masabumi Minami

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Monocyte chemoattractant protein-1 (MCP-1, CCL2) is a well-defined chemokine implicated in the pathology of various neurodegenerative diseases and brain injuries, such as Alzheimer's disease, multiple sclerosis, stroke, and traumatic injury. We investigated the effect of the activation of P2 purinoceptors on MCP-1 production in rat corticostriatal slice cultures. Treatment with adenosine 5′-O-(3-thiotriphosphate) (ATPγS), a hydrolysis-resistant adenosine triphosphate (ATP) analog, induced MCP-1 production in astrocytes. The induction was in a concentration-dependent manner and was antagonized by a P2 purinoceptor antagonist pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid. The inhibition of an extracellular signal-regulated kinase (ERK) pathway by PD98059 and U0126 significantly suppressed ATPγS-induced MCP-1 mRNA expression and protein production, while inhibition of c-Jun N-terminal kinase by SP600125 resulted in the partial suppression. Conversely, SB203580, a p38 mitogen-activated protein (MAP) kinase inhibitor, significantly enhanced ATPγS-induced MCP-1 production. Similar effects of ERK and p38 MAP kinase inhibitors on MCP-1 production were observed in the slices stimulated by ATP and BzATP. These results demonstrate that astrocytic MCP-1 production induced by P2 purinoceptor stimulation is reciprocally regulated by ERK and p38 MAP kinases in the organotypic slice cultures.

Original languageEnglish
Pages (from-to)1573-1581
Number of pages9
JournalJournal of Neuroscience Research
Volume87
Issue number7
DOIs
Publication statusPublished - May 15 2009
Externally publishedYes

Fingerprint

Chemokine CCL2
Extracellular Signal-Regulated MAP Kinases
p38 Mitogen-Activated Protein Kinases
Mitogens
Purinergic P2 Receptors
Protein Kinase Inhibitors
Purinergic P2 Receptor Antagonists
Adenosine Triphosphate
Proteins
Pyridoxal Phosphate
JNK Mitogen-Activated Protein Kinases
Chemokines
Astrocytes
Neurodegenerative Diseases
Brain Injuries
Multiple Sclerosis
Alzheimer Disease
Hydrolysis
Stroke
Pathology

Keywords

  • Astrocyte
  • ATP
  • Chemokine
  • MCP-1
  • Organotypic slice culture

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Reciprocal regulation of ATPγS-induced monocyte chemoattractant protein-1 production by ERK and p38 MAP kinasesin rat corticostriatal slice cultures. / Katayama, Takahiro; Ito, Misato; Kaneko, Shuji; Satoh, Masamichi; Uehara, Takashi; Minami, Masabumi.

In: Journal of Neuroscience Research, Vol. 87, No. 7, 15.05.2009, p. 1573-1581.

Research output: Contribution to journalArticle

Katayama, Takahiro ; Ito, Misato ; Kaneko, Shuji ; Satoh, Masamichi ; Uehara, Takashi ; Minami, Masabumi. / Reciprocal regulation of ATPγS-induced monocyte chemoattractant protein-1 production by ERK and p38 MAP kinasesin rat corticostriatal slice cultures. In: Journal of Neuroscience Research. 2009 ; Vol. 87, No. 7. pp. 1573-1581.
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