Proteomic analysis of neonatal mouse brain: evidence for hypoxia- and ischemia-induced dephosphorylation of collapsin response mediator proteins.
Perinatal hypoxia and ischemia (HI) are a significant cause of mortality and morbidity. To understand the molecular mechanisms for HI-induced brain damage, here we used a proteomic approach to analyze the alteration and modification of proteins in neonatal mouse brain 24 h after HI treatment. Significant changes of collapsin response mediator proteins (CRMPs) were observed in HI brain. CRMPs are a family of cytosolic proteins involved in axonal guidance and neuronal outgrowth. We found that CRMP2, CRMP4 and CRMP5 proteins were altered post-translationally after HI treatment. Mass spectrometric and Western blot analyses detected hypophosphorylated CRMP proteins after HI. Further analysis of CRMP kinases indicated inactivation of cyclin dependent kinase 5 (CDK5), a priming kinase of CRMPs and a neuronal specific kinase that plays pivotal roles in neuronal development and survival. The reduction of CDK5 activity was associated with underexpression of its activator p35. Taken together, our findings reveal HI-induced dephosphorylation of CRMPs in neonatal brain and suggest a novel mechanism for this modification. Hypophosphorylated CRMPs might be implicated in the pathogenesis of HI-related neurological disorders.
Zhou
Yuan
Y
Department of Anatomy, The University of Hong Kong, Hong Kong.
Bhatia
Inderjeet
I
Cai
Zhen
Z
He
Qing-Yu
QY
Cheung
Pik-To
PT
Chiu
Jen-Fu
JF
D000469:Alkaline Phosphatase / Q000737:chemistry; D000581:Amidohydrolases / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D051360:Cyclin-Dependent Kinase 5 / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D006624:Hippocampus / Q000378:metabolism; D006867:Hydrolases; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D010748:Phosphopeptides / Q000032:analysis; D010766:Phosphorylation; D010770:Phosphotransferases / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D020543:Proteome / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
C492236:Cdk5r1 protein, mouse; C526904:Dpysl3 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D010748:Phosphopeptides; D020543:Proteome; C095114:collapsin response mediator protein-2; D010770:Phosphotransferases; D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse; C501733:Dpysl5 protein, mouse; D006867:Hydrolases; D000469:Alkaline Phosphatase; D000581:Amidohydrolases