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Ethyl pyruvate inhibits HMGB1 phosphorylation and release by chelating calcium

Title
Ethyl pyruvate inhibits HMGB1 phosphorylation and release by chelating calcium
Authors
Shin J.-H.Kim I.-D.Kim S.-W.Lee H.-K.Jin Y.Park J.-H.Kim T.-K.Suh C.-K.Kwak J.Lee K.-H.Han P.-L.Lee J.-K.
Ewha Authors
한평림
SCOPUS Author ID
한평림scopus
Issue Date
2014
Journal Title
Molecular medicine (Cambridge, Mass.)
ISSN
1528-3658JCR Link
Citation
vol. 20, pp. 649 - 657
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Ethyl pyruvate (EP), a simple aliphatic ester of pyruvic acid, has been shown to have antiinflammatory effects and to confer protective effects in various pathological conditions. Recently, a number of studies have reported EP inhibits high mobility group box 1 (HMGB1) secretion and suggest this might contribute to its antiinflammatory effect. Since EP is used in a calcium-containing balanced salt solution (Ringer solution), we wondered if EP directly chelates Ca(2+) and if it is related to the EP-mediated suppression of HMGB1 release. Calcium imaging assays revealed that EP significantly and dose-dependently suppressed high K(+)-induced transient [Ca(2+)]i surges in primary cortical neurons and, similarly, fluorometric assays showed that EP directly scavenges Ca(2+) as the peak of fluorescence emission intensities of Mag-Fura-2 (a low-affinity Ca(2+) indicator) was shifted in the presence of EP at concentrations of ≥7 mmol/L. Furthermore, EP markedly suppressed the A23187-induced intracellular Ca(2+) surge in BV2 cells and, under this condition, A23187-induced activations of Ca(2+)-mediated kinases (protein kinase Cα and calcium/calmodulin-dependent protein kinase IV), HMGB1 phosphorylation and subsequent secretion of HMGB1 also were suppressed. (A23187 is a calcium ionophore and BV2 cells are a microglia cell line.) Moreover, the above-mentioned EP-mediated effects were obtained independent of cell death or survival, which suggests that they are direct effects of EP. Together, these results indicate that EP directly chelates Ca(2+), and that it is, at least in part, responsible for the suppression of HMGB1 release by EP.
DOI
10.2119/molmed.2014.00039
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일반대학원 > 뇌·인지과학과 > Journal papers
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