Proteomic Analysis of Neonatal Mouse Brain: Evidence for Hypoxia- and Ischemia-Induced Dephosphorylation of Collapsin Response Mediator Proteins

Zhou, Yuan; Bhatia, Inderjeet; Cai, Zhen; He, Qing‐Yu; Cheung, Pik-To; Chiu, Jen‐Fu

doi:10.1021/pr800108k

Cited by 27 publications

(20 citation statements)

References 44 publications

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“…In another hypoxia-ischemia model, hypophosphorylation of CRMP2 at Thr514 also occurred in the neonatal brain after both unilateral ligation of CCA and hypoxic gas exposure. [30] In our study, we demonstrated hypophosphorylation of CRMP2 at Thr514 in the retina after bilateral ligation of the ICA for at least 2 weeks, which corresponded to other researches [Figure 5c]. On the contrary, Hou et al .…”

Section: Discussionsupporting

confidence: 90%

Collapsin Response Mediator Protein-2-induced Retinal Ischemic Injury in a Novel Mice Model of Ocular Ischemia Syndrome

Wang

Xie

et al. 2017

Chinese Medical Journal

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Background:Collapsin response mediator protein-2 (CRMP2) has been shown to be involved in ischemia/hypoxia (IH) injury. We determined whether CRMP2 modulates ischemic injury in the retinal of Ocular ischemic syndrome (OIS). This study was to explore the molecular mechanisms underlying OIS in a novel mice model.Methods:Experiments were performed on adult male C57/BL6 mice that received bilateral internal carotid arteries ligation for 1, 2, or 4 weeks. The mice received injection of calpeptin group before occlusion for 4 weeks or not. The expression of CRMP2 in the retinal was examined by western blotting (WB) analysis and immunohistochemical analysis (IHC). The effects of ischemic injury on retinal were evaluated by fundus examination, fundus fluorescein angiography, electroretinogram, cell counting of retinal ganglion cell (RGC), and measurement of the thickness of the retina.Results:The veins dilated after chronic ischemia. In the electroretinography, the amplitudes of a- and b-waves kept diminishing in an ischemia time-dependent manner. Moreover, the tail vein-retinal circulation time prolonged in the 1- and 2-week group. In comparison, thickness of the retina decreased gradually with the ischemia time elapsed. WB analysis showed the CRMP2 and p-CRMP2 levels decreased in the 2- and 4-week groups. The results of IHC analysis were compatible with our results of WB. The loss of RGCs, decrease of the total reaction time and reduction of CRMP2 was alleviated by intravitreal injection of calpeptin.Conclusions:These results revealed that bilateral ligation of the internal carotid artery causes retinal ischemia in mice. Moreover, CRMP2 might play a pivotal role during the ischemic injury in the retina and inhibit the cleavage of CRMP2 can ameliorate the IH injury.

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Section: Discussionsupporting

confidence: 90%

Collapsin Response Mediator Protein-2-induced Retinal Ischemic Injury in a Novel Mice Model of Ocular Ischemia Syndrome

Wang

Xie

et al. 2017

Chinese Medical Journal

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“…These findings in chick spinal cord are consistent with the regulation of phosphorylation of Crmps observed following hypoxic-ischemic insult in rats where neural repair is very limited and Crmp-2 seems to be hypo-rather than hyperphosphorylated (Zhou et al, 2008).…”

Section: Crmp-2 Forms Are Differently Regulated Following Spinal-cordsupporting

confidence: 88%

Post‐translational regulation of Crmp in developing and regenerating chick spinal cord

Gögel¹,

Lange²,

Leung³

et al. 2010

Developmental Neurobiology

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It is becoming apparent that regulation at the protein level plays crucial roles in developmental and pathological processes. Therefore, we performed a proteomics screen to identify proteins that are differently expressed or modified at stages of development permissive (E11) and nonpermissive for regeneration (E15) of the chick spinal cord. Proteins regulated either developmentally or in response to spinal-cord injury included collapsin-response-mediator proteins (Crmps), known to modulate microtubule dynamic and axonal growth. No significant changes in Crmp transcripts following injury were observed, indicating regulation mainly at the protein level. Analysis of Crmp-2 protein and its phosphorylated forms, pS522 and pT514, showed that Crmp-2 is developmentally regulated and also expressed in neural progenitors in vivo and in neurospheres. Its cellular localization changed both with development and following spinal-cord injury. In addition, although overall levels of Crmp-2 expression were not affected by injury, abundance of certain phosphorylated forms was altered. pT514 Crmp-2 appeared to be associated with dividing neural progenitors and was greatly reduced at nonpermissive stages for regeneration, whereas it did not seem affected by injury. In contrast, phosphorylation of Crmp-2 at S522 was upregulated early after injury in regenerating spinal cords and the ratio between phosphorylated to total Crmp-2 increased, as indicated by 2D Western blots. Altogether, this study shows highly dynamic regulation of Crmp-2 forms during development and identifies post-translational changes in Crmp-2 as putative contributors to the maintenance of spinal-cord regenerative ability, possibly via a transient stabilization of the neuronal cytoskeleton.

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“…To date, the application of shotgun proteomics to analyze protein phosphorylation has been extended into many areas of the nervous system, including regulation of synaptic transmission through the activation of kinases and phosphatases (Munton et al, 2007; Trinidad et al, 2008), glutamate receptor signaling, and neural development (Ballif et al, 2004; Liao et al, 2008a), as well as neurological disorders (Zhou et al, 2008). While the focus has been on large scale identification of phosphopeptides and phosphorylation sites, an emerging trend is the quantitation of phosphorylation changes under different biological conditions.…”

Section: Application Of Shotgun Proteomics In Neurosciencementioning

confidence: 99%

Shotgun Proteomics in Neuroscience

Liao

McClatchy

Yates

2009

Neuron

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Mass spectrometry-based proteomics is increasingly used to address basic and clinical questions in biomedical research through studies of differential protein expression, protein-protein interactions, and post-translational modifications. The complex structural and functional organization of the human brain warrants the application of high-throughput, systematic approaches to understand the functional alterations under normal physiological conditions and the perturbations of neurological diseases. This primer focuses on shotgun proteomics based tandem mass spectrometry for the identification of proteins in a complex mixture. It describes the basic concepts of protein differential expression analysis and post-translational modification analysis and discusses several strategies to improve the coverage of the proteome.

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Proteomic Analysis of Neonatal Mouse Brain: Evidence for Hypoxia- and Ischemia-Induced Dephosphorylation of Collapsin Response Mediator Proteins

Cited by 27 publications

References 44 publications

Collapsin Response Mediator Protein-2-induced Retinal Ischemic Injury in a Novel Mice Model of Ocular Ischemia Syndrome

Collapsin Response Mediator Protein-2-induced Retinal Ischemic Injury in a Novel Mice Model of Ocular Ischemia Syndrome

Post‐translational regulation of Crmp in developing and regenerating chick spinal cord

Shotgun Proteomics in Neuroscience

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