Cold stress protein RBM3 responds to temperature change in an ultra-sensitive manner in young neurons.
Extremely mild hypothermia to 36.0 °C is not thought to appreciably differ clinically from 37.0 °C. However, it is possible that 36.0 °C stimulates highly sensitive hypothermic signaling mechanism(s) and alters biochemistry. To the best of our knowledge, no such ultra-sensitive pathway/mechanisms have been described. Here we show that cold stress protein RNA binding motif 3 (RBM3) increases in neuron and astrocyte cultures maintained at 33 °C or 36 °C for 24 or 48 h, compared to 37 °C controls. Neurons cultured at 36 °C also had increased global protein synthesis (GPS). Finally, we found that melatonin or fibroblast growth factor 21 (FGF21) augmented RBM3 upregulation in young neurons cooled to 36 °C. Our results show that a 1 °C reduction in temperature can induce pleiotropic biochemical changes by upregulating GPS in neurons which may be mediated by RBM3 and that this process can be pharmacologically mimicked and enhanced with melatonin or FGF21.
University of Pittsburgh School of Medicine, Safar Center for Resuscitation Research, 200 Hill Building, 3434 Fifth Avenue, Pittsburgh, PA 15260, United States; University of Pittsburgh School of Medicine, Department of Critical Care Medicine, 3550 Terrace Street, Pittsburgh, PA 15261, United States. Electronic address: jacksontc@upmc.edu.
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Jackson
University of Pittsburgh School of Medicine, Safar Center for Resuscitation Research, 200 Hill Building, 3434 Fifth Avenue, Pittsburgh, PA 15260, United States; University of Pittsburgh School of Medicine, Department of Pediatrics, 4401 Penn Avenue, Pittsburgh, PA 15224, United States.
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Manole
University of Pittsburgh School of Medicine, Department of Pharmacology and Chemical Biology, Bridgeside Point Building 1, 100 Technology Drive, Pittsburgh, PA 15219, United States.
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Kotermanski
University of Pittsburgh School of Medicine, Department of Pharmacology and Chemical Biology, Bridgeside Point Building 1, 100 Technology Drive, Pittsburgh, PA 15219, United States.
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Jackson
University of Pittsburgh School of Medicine, Safar Center for Resuscitation Research, 200 Hill Building, 3434 Fifth Avenue, Pittsburgh, PA 15260, United States; University of Pittsburgh School of Medicine, Department of Critical Care Medicine, 3550 Terrace Street, Pittsburgh, PA 15261, United States.
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Clark
University of Pittsburgh School of Medicine, Safar Center for Resuscitation Research, 200 Hill Building, 3434 Fifth Avenue, Pittsburgh, PA 15260, United States; University of Pittsburgh School of Medicine, Department of Critical Care Medicine, 3550 Terrace Street, Pittsburgh, PA 15261, United States.
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Kochanek
D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004622:Embryo, Mammalian; D005260:Female; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007036:Hypothermia, Induced / Q000379:methods; D008550:Melatonin / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013696:Temperature; D013997:Time Factors
D000975:Antioxidants; C533319:RBM3 protein, rat; D016601:RNA-Binding Proteins; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D008550:Melatonin
CIRBP; FGF21; RBM3; global protein synthesis; hypothermia; targeted temperature management