Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 30, Issue 4, Pages 1014-1022Publisher
KARGER
DOI: 10.1159/000341478
Keywords
Indomethacin; Protein phosphatase 1; Protein phosphatase 2A; Protein tyrosine phosphatase 1B; Ca2+/calmodulin-dependent protein kinase II
Categories
Ask authors/readers for more resources
Background/Aims: We have shown that indomethacin has the potential to activate Ca2+/calmodulin-dependent protein kinase II (CaMKII), regardless of cyclooxygenase (COX) inhibition. To understand the underlying mechanism, the present study investigated the effect of indomethacin on protein phosphatases such as protein phosphatase 1 (PP1), protein phosphatase 2A (PP2A), and protein tyrosine phosphatase 1B (PTP1B). Methods: Activity of CaMKII was assayed in cultured rat hippocampal neurons and under the cell-free conditions. Activities of protein phosphatases were monitored under the cell-free conditions. Indomethacin binding assay was carried out using a fluorescein-conjugated indomethacin. Results: Indomethacin enhanced CaMKII activity in cultured rat hippocampal neurons, that is abolished the CaMKII inhibitor KN-93. In the cell-free assay, no CaMKII activation was obtained with indomethacin, but indomethacin otherwise inhibited PP1 in a concentration (10 mu M-1 mM)-dependent manner, the maximum reaching 70% of basal levels. This indicates that indomethacin indirectly activates CaMKII due to PP1 inhibition. Likewise, indomethacin still inhibited PP2A and PTP1B in a concentration (10 mu M-1 mM)-dependent manner, reaching 80 and 10% of basal levels at 1 mM, respectively. In the indomethacin binding assay, indomethacin bound to all the investigated protein phosphatases. Conclusion: The results of the present study indicate that indomethacin inhibits PP1, PP2A, and PTP1B, possibly through its direct binding and that the inhibitory effect of indomethacin on PP1 could cause indirect CaMKII activation. This may represent the novel indomethacin action. Copyright (C) 2012 S. Karger AG, Basel
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available