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Inhibition of Calcineurin A by FK506 Suppresses Seizures and Reduces the Expression of GluN2B in Membrane Fraction

Wen, Yuetao, Fu, Pengfei, Wu, Kunlun, Si, Kaichuang, Xie, Yanfeng, Dan, Wei, Zhan, Yan, Shi, Quanhong·2017·Neurochemical Research
DOI 10.1007/s11064-017-2221-0
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Abstract

FK506, a calcineurin inhibitor, shows neuroprotective effects and has been associated with neurodegenerative diseases. Calcineurin A (CaNA), a catalytic subunit of calcineurin, mediates the dephosphorylation of various proteins. N-methyl-D-aspartate receptor (GluN) is closely related to epileptogenesis, and various phosphorylation sites of GluN2B, a regulatory subunit of the GluN complex, have different functions. Thus, we hypothesized that one of the potential anti-epileptic mechanisms of FK506 is mediated by its ability to promote the phosphorylation of GluN2B and reduce the expression of GluN2B in membrane fraction by down-regulating CaNA. CaNA expression was increased in the cortex of patients with temporal lobe epilepsy and pentylenetetrazol (PTZ)-induced epileptic models. CaNA was shown to be expressed in neurons using immunofluorescence staining. According to our behavioral observations, epileptic rats exhibited less severe seizures and were less sensitive to PTZ after a systemic injection of FK506. The levels of phosphorylated GluN2B were decreased in epileptic rats but increased after the FK506 treatment. Moreover, there was no difference in the total GluN2B levels before and after FK506 treatment. However, the expression of GluN2B in membrane fraction was suppressed after FK506 treatment. Based on these results, FK506 may reduce the severity and frequency of seizures by reducing the expression of GluN2B in membrane fraction.

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Metadata

Authors
Wen, Y., Fu, P., Wu, K., Si, K., Xie, Y., Dan, W., Zhan, Y., & Shi, Q.
Venue
Neurochemical Research
Publisher
Springer Science and Business Media LLC
Published
2017-03-15
Volume
42
Issue
8
Pages
2154-2166
ISSN
  • 0364-3190
  • 1573-6903
DOI
10.1007/s11064-017-2221-0
Cited by
13
References
2
Language
en
Licence
www.springer.com/tdm (unspecified)
Funders
Chongqing Municipal Public Health Bureau, Chongqing People’s Municipal Government (2013-1-005)

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