Chronic morphine treatment induces over-expression of HSP70 in mice striatum related with abnormal ubiquitin-proteasome degradation

Background: It has been shown that opioid dependence-related neuronal plasticity may rely not only on protein synthesis, but also on protein degradation, mainly mediated by ubiquitin-proteasome system (UPS). The aim of the present study was to determine the effect of morphine on the regulation of protein degradation in the brain and to determine which proteins are involved in the underlying mechanism. Methods: Mice were given chronic morphine administration and the state of morphine dependence was confirmed by induction of naloxone-precipitated withdrawal jumping. The level of ubiquitinated proteins in the striatum and spinal cord of morphine-dependent mice was detected by Western blotting. One of the abnormal-ubiquitinated proteins in mice striatum was identified by electrospray ionization quadrupole time-of-flight tandem mass spettrometry and the result was further confirmed by Western blotting and immunofluorescence method. Results: We found that the expression of some ubiquitinated proteins was clearly decreased in the striatum of morphine-depnendent mice, but not in the spinal cord. And we identified a ubiquitinated protein (>79 kDa) decreased in the striatum as heat shock cognate 70 protein, one member of the 70 kDa family of heat shock proteins (HSP70). Moreover, we confirmed the level of HSP70 protein was significantly increased in mice striatum. Conclusions: These data strongly suggest morphine-induced HSP70 overexpression in the striatum is closely related with its abnormal degradation by UPS and it seems to be an important mechanism associated with morphine dependence. (C) 2014 Elsevier Ireland Ltd. All rights reserved.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000336708000008&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Substance AbusePsychiatrySCI(E)PubMedSSCI3ARTICLEyanghaiyu@yahoo.com53-5913