Retracted: Phosphorylated CaMKII post‐synaptic binding to NR2B subunits in the anterior cingulate cortex mediates visceral pain in visceral hypersensitive rats
Authors: Zhijun Cao
Bing Cao
Ying Li
Haiyan Liu
Shengliang Chen
Xu Zhang
Jin Liu
Journal: Journal of Neurochemistry (2012)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: NR2B subunit; NMDA receptor; anterior cingulate cortex; ACC; viscerally hypersensitive
Affiliations: Neuroscience Laboratory, Department of Biology and Chemistry, the City University of Hong Kong, Kowloon, Hong Kong. 

Abstract:  The NR2B subunit of NMDA receptor in the anterior cingulate cortex (ACC) is up-regulated in viscerally hypersensitive (VH) rats induced by colonic anaphylaxis. It plays a critical role in modulation of ACC sensitization and visceral pain responses. Given the key role of calcium/calmodulin-dependent protein kinase II (CaMKII) in synaptic plasticity and behavior learning and memory, we hypothesize that phosphorylation of CaMKII binding to NR2B mediates visceral pain in VH states. We performed in vivo electroporation of CaMKII siRNA produced inhibition of colorectal distension-induced visceromotor response in the VH rats. The NR2B, CaMKII and P-CaMKII-Thr²⁸⁶ protein levels were increased in 180%, 220% and 304% fold in the post-synaptic density (PSD) fraction in VH rats separately. Western blotting following co-immunoprecipitation showed that P-CaMKII-Thr²⁸⁶ bound to NR2B in the PSD, which was increased to 267% of control in VH rats. Administration of CaMKII antagonist Antennapedia-CaMKIINtide suppressed visceromotor response in VH rats in parallel with decrease of NR2B levels and reduction of the NR2B-P-CaMKII-Thr²⁸⁶ protein complex in PSD. In conclusion, CaMKII is a critical signaling molecule in the ACC glutamatergic synaptic transmission and phosphorylation of CaMKII at Thr286, which binds to NR2B subunit at post-synaptic site, modulates visceral pain in viscerally hypersensitive state. 

Retracted: Yes

PubPeer comments:
 Fig 1  (c) Representative electromyograms of the VMR to graded-pressure CRD in VH rats treated with vehicle or glutamate, or with microelectroporation of CaMKII siRNA before glutamate injection. Below, Fig 1,  (A) A representative abdominal muscle electromyogram of the VMR to graded-pressure CRD recorded from the external oblique pelvic muscle in normal and viscerally hypersensitive rats . From  Anterior cingulate cortex modulates visceral pain as measured by visceromotor responses in viscerally hypersensitive rats [(Cao et al. 2008)] . ![file] Unexpected similarity between two CaMKII siRNA glutamate conditions in the present paper, and two Normal conditions from four years earlier. , 
 Fig 1(a). ![file] Are the 20- and 40-mm Hg distension EMGs supposed to be identical? , 
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 2020 retraction. https: onlinelibrary.wiley.com doi full 10.1111 jnc.14995 The Article has been retracted by agreement between the lead author Ying Li (the u201cLead Authoru201d), the Journalu2019s Editor in Chief, Ju00f6rg B. Schulz, and John Wiley Sons Ltd (together the u201cPartiesu201d). The Lead Author had been notified of some anomalies in the Article. Specifically, in Figure 1c, the electromyograms of VHu2010Gluu2010CaMKII siRNA rats at pressure 40 mmHg and 60 mmHg were similar to electromyograms in Figure 1a used in a previous publication by the Lead Author (Cao et al., 2008): Fig 1c (from the Article),  Representative electromyograms of the VMR to gradedu2010pressure CRD in VH rats treated with vehicle or glutamate, or with microelectroporation of CaMKII siRNA before glutamate injection. Compared with: Figure 1a,  A representative abdominal muscle electromyogram of the VMR to gradedu2010pressure CRD recorded from the external oblique pelvic muscle in normal and viscerally hypersensitive rats . From:  Anterior cingulate cortex modulates visceral pain as measured by visceromotor responses in viscerally hypersensitive rats , by Zhijun Cao, Xiaoyin Wu, Shengliang Chen, Jing Fan, Rui Zhang, Chung Owyang, Ying Li, Gastroenterology 134(2), 535u2010543, 2008 , 535u2010543, 2008 : Repeated electromyogram lane VHu2010vehicle for 20 and 40 mm Hg, respectively. In relation to the western blot images of Figure 3b and Figure 5a in the Article, the erroneous instances are shown below. Figure 3b of the Article: Western blot lanes flipped and or repeated with lanes shown in Figure 5a of the same article. Figure 5a of the Article The data were compiled by the Lead Authoru2019s research students at the time, some of whom the Lead Author has lost contact with and thus is unable to clarify how these mistakes happened. The Lead Author has taken responsibility by requesting retraction of the Article since the above mentioned data could not be verified, and truly regrets that this error has happened in his laboratory. ,