title: The RNA-binding protein RBM3 is involved in hypothermia induced neuroprotection.
abstract: Induced hypothermia is the only therapy with proven efficacy to reduce brain damage after perinatal asphyxia. While hypothermia down-regulates global protein synthesis and cell metabolism, low temperature induces a small subset of proteins that includes the RNA-binding protein RBM3 (RNA-binding motif protein 3), which has recently been implicated in cell survival. Here, immunohistochemistry of the developing postnatal murine brain revealed a spatio-temporal neuronal RBM3 expression pattern very similar to that of doublecortin, a marker of neuronal precursor cells. Mild hypothermia (32°C) profoundly promoted RBM3 expression and rescued neuronal cells from forced apoptosis as studied in primary neurons, PC12 cells, and cortical organotypic slice cultures. Blocking RBM3 expression in neuronal cells by specific siRNAs significantly diminished the neuroprotective effect of hypothermia while vector-driven RBM3 over-expression reduced cleavage of PARP, prevented internucleosomal DNA fragmentation, and LDH release also in the absence of hypothermia. Together, neuronal RBM3 up-regulation in response to hypothermia apparently accounts for a substantial proportion of hypothermia-induced neuroprotection.
authors.affiliation: Children's University Hospital Basel, Spitalstrasse 33, 4031 Basel, Switzerland. sophorn.chip@unibas.ch
authors.forename: Sophorn
authors.initials: S
authors.lastname: Chip
authors.forename: Andrea
authors.initials: A
authors.lastname: Zelmer
authors.forename: Omolara O
authors.initials: OO
authors.lastname: Ogunshola
authors.forename: Ursula
authors.initials: U
authors.lastname: Felderhoff-Mueser
authors.forename: Cordula
authors.initials: C
authors.lastname: Nitsch
authors.forename: Christoph
authors.initials: C
authors.lastname: Bührer
authors.forename: Sven
authors.initials: S
authors.lastname: Wellmann
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D000089662:Doublecortin Protein; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D007036:Hypothermia, Induced / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D009924:Organ Culture Techniques / Q000379:methods; D016716:PC12 Cells; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats
chemical_list: C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D018696:Neuroprotective Agents; D016601:RNA-Binding Proteins; C484384:Rbm3 protein, mouse