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Up‐regulation of Na + –Ca 2+ exchange activity by interferon‐γ in cultured rat microglia
Author(s) -
Nagano Takayuki,
Kawasaki Yasushi,
Baba Akemichi,
Takemura Motohiko,
Matsuda Toshio
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02511.x
Subject(s) - staurosporine , protein kinase c , microglia , extracellular , tyrosine kinase , protein kinase a , cycloheximide , microbiology and biotechnology , calphostin c , intracellular , chemistry , ouabain , thapsigargin , kinase , biology , signal transduction , endocrinology , medicine , protein biosynthesis , immunology , sodium , organic chemistry , inflammation
The Na + –Ca 2+ exchanger (NCX) plays a role in regulating intracellular Ca 2+ concentration, but little is known about NCX in microglia. We examined mRNA expression of NCX isoforms in cultured rat microglia and the effect of interferon‐γ (IFN‐γ) on NCX activity. RT–PCR showed that all of the known NCX isoforms, NCX1–3, are expressed in cultured microglia. Ouabain and monensin increased 45 Ca 2+ uptake and intracellular Ca 2+ concentration in microglia, suggesting the presence of NCX activity in the reverse mode. Treatment with IFN‐γ (100 U/mL) caused a biphasic increase in NCX activity. The transient increase in NCX activity by IFN‐γ for 1 h was blocked by the protein kinase C (PKC) inhibitors, staurosporine and GF109203X, and the tyrosine kinase inhibitor, herbimycin A. The delayed increase in NCX activity by IFN‐γ for 24 h was blocked by the protein synthesis inhibitor cycloheximide and actinomycin D. Treatment with IFN‐γ for 24 h increased NCX mRNA and protein levels. The increase in NCX activity and NCX protein by IFN‐γ for 24 h was blocked by staurosporine, GF109203X, herbimycin A and the extracellular signal‐regulated kinase inhibitor, PD98059. These findings suggest that NCX is up‐regulated by IFN‐γ in a biphasic manner in microglia. Moreover, PKC and tyrosine kinase are involved in the up‐regulation of NCX and the extracellular signal‐regulated protein kinase is also involved in the delayed increase in NCX activity.