Proteomic analysis of hypoxia/ischemia-induced alteration of cortical development and dopamine neurotransmission in neonatal rat

Xiaoming Hu, Harriett C. Rea, John E. Wiktorowicz, J. Regino Perez-Polo

    Research output: Contribution to journalArticle

    40 Citations (Scopus)

    Abstract

    Perinatal hypoxia/ischemia (HI) is a common cause of neurological deficits in children. Our goal was to elucidate the underlying mechanisms that contribute to the neurological sequelae of HI-induced brain injury. HI was induced by permanent ligation of the left carotid artery followed by 90 min of hypoxia (7.8% O2) in female P7 rats. A two-dimensional differential proteome analysis was used to assess changes in protein expression in cortex 2 h after HI. In total, 17 proteins reflecting a 2-fold or higher perturbation of expression after HI as compared to sham-treated pups were identified by mass spectrometry. Of the altered proteins, 14-3-3ε and TUC-2, both playing an important role in the development of the central nervous system, decrease after HI, consistent with an early disturbance of cortical development. Also affected, DARPP-32 and α-synuclein, two proteins important for dopamine neurotransmission, increased more than 2-fold 2 h after HI injury. The differential expression of these proteins was validated by individual Western blot assays. The expression of several metabolic enzymes and translational factors was also perturbed early after HI brain injury. These findings provide initial insights into the mechanisms underlying neurodegenerative events after HI and may allow for the rational design of therapeutic strategies that enhance neuronal adaptation and compensation after HI.

    Original languageEnglish (US)
    Pages (from-to)2396-2404
    Number of pages9
    JournalJournal of Proteome Research
    Volume5
    Issue number9
    DOIs
    StatePublished - Sep 2006

    Fingerprint

    Synaptic Transmission
    Proteomics
    Rats
    Dopamine
    Ischemia
    Brain
    Proteins
    Synucleins
    14-3-3 Proteins
    Neurology
    Proteome
    Mass spectrometry
    Assays
    Brain Injuries
    Hypoxia
    Enzymes
    Carotid Arteries
    Ligation
    Mass Spectrometry
    Central Nervous System

    Keywords

    • Cortex
    • Hypoxia/ischemia
    • Proteomics

    ASJC Scopus subject areas

    • Genetics
    • Biotechnology
    • Biochemistry

    Cite this

    Proteomic analysis of hypoxia/ischemia-induced alteration of cortical development and dopamine neurotransmission in neonatal rat. / Hu, Xiaoming; Rea, Harriett C.; Wiktorowicz, John E.; Perez-Polo, J. Regino.

    In: Journal of Proteome Research, Vol. 5, No. 9, 09.2006, p. 2396-2404.

    Research output: Contribution to journalArticle

    Hu, Xiaoming ; Rea, Harriett C. ; Wiktorowicz, John E. ; Perez-Polo, J. Regino. / Proteomic analysis of hypoxia/ischemia-induced alteration of cortical development and dopamine neurotransmission in neonatal rat. In: Journal of Proteome Research. 2006 ; Vol. 5, No. 9. pp. 2396-2404.
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