Abstract
Background: Induced hypothermia is the only therapy with proven efficacy to reduce brain damage after perinatal asphyxia. While hypothermia downregulates global protein synthesis and cell metabolism, low temperature induces a small subset of proteins that includes the RNA-binding protein RBM3, which is transcriptionally induced also in response to hypoxia and has recently been implicated in cell survival.
Methods/results: We studied RBM3 expression in the developing murine brain by immunohistochemistry and found RBM3 widely expressed in neurons of the hippocampus, the subventricular zone, and the cerebellum during the first postnatal days. In adult brains, RBM3 was present only in neuronal precursor and stem cells, characterized by the presence of doublecortin. Hypothermia profoundly promoted RBM3 expression in juvenile as well as in mature neurons, and hypothermia-induced RBM3 expression was associated with protection of primary neurons and neuronal cell lines from forced apoptosis. Blocking RBM3 expression by siRNAs in neuronal cells significantly diminished the neuroprotective effect of hypothermia while vector-driven RBM3 overexpression prevented activation of caspase-3.
Conclusion: Together, the RNA-binding protein RBM3 protects neuronal cells from apoptosis. RBM3 upregulation apparently accounts for a substantial proportion of hypothermia-induced neuroprotection.
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Wellmann, S., Zelmer, A., Nitsch, C. et al. 193 The Rna-Binding Protein Rbm3 is Involved in Hypothermia Induced Neuroprotection. Pediatr Res 68 (Suppl 1), 101 (2010). https://doi.org/10.1203/00006450-201011001-00193
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DOI: https://doi.org/10.1203/00006450-201011001-00193
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