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Abstract #45928 Published in IGR 13-2
Elevation of p-NR2A(S1232) by Cdk5/p35 contributes to retinal ganglion cell apoptosis in a rat experimental glaucoma model
Chen J; Miao Y; Wang X-H; Wang ZNeurobiology of Disease 2011; 43: 455-464
Glaucoma, mainly caused by high intraocular pressure (IOP), is characterized by apoptotic death of retinal ganglion cells (RGCs). We investigated the possible involvement of cyclin-dependent kinase 5 (Cdk5) and its activator p35, which have been implicated in a variety of neurological disorders, in RGC apoptosis in a rat experimental glaucoma model reproduced by blocking episcleral veins. Cholera toxin B subunit (CTB) retrogradely labeled RGCs displayed a dramatic reduction in number both in the central and peripheral retina on day 14 (D14) (P < 0.05 vs control), D21 (P < 0.01 vs control) and D28 (P < 0.001 vs control) after operation. Terminal dUTP nick end labeling (TUNEL)-positive cells were detected on D14 both in the central and peripheral regions, and numerous TUNEL-positive cells were found on D21 and D28 in both the regions (P all < 0.001 vs control). As compared with the control eyes, the expression level of Cdk5 was significantly increased on D21 (P < 0.001), whereas that of p35 displayed a marked increase on D14 (P < 0.01) and D21 (P < 0.001). Meanwhile, both NR2A and p-NR2A(S1232) increased from D14 onwards (P < 0.01 to 0.001). Co-immunoprecipitation indicated a direct interaction between Cdk5 and p-NR2A(S1232). Intraperitoneal injection of the Cdk5 inhibitor roscovitine remarkably inhibited RGC apoptosis (P < 0.001 vs vehicle group) and increased the number of CTB-labeled RGCs (P < 0.05 to 0.01 vs vehicle group) in whole flat-mounted retinas, which was accompanied by a significant decrease in expression levels of p35 and p-NR2A(S1232) (P all < 0.01 vs vehicle group). Our results suggest that elevation of p-NR2A(S1232) by Cdk5/p35 contributes to RGC apoptotic death in experimental glaucoma rats, which could be effectively ameliorated by inhibiting Cdk5/p35.
Z. Wang. Institutes of Brain Science, Institute of Neurobiology and State Key Laboratory of Medical Neurobiol, . Email: zfwang@fudan.edu.cn
Classification:
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
3.6 Cellular biology (Part of: 3 Laboratory methods)
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
11.8 Neuroprotection (Part of: 11 Medical treatment)
