Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 13-lined ground squirrel (Ictidomys tridecemlineatus) is capable of entering into extended periods of torpor during winter hibernation. The state of torpor represents a hypometabolic shift wherein the rate of oxygen consuming processes are strongly repressed in an effort to maintain cellular homeostasis as the availability of food energy becomes limited. We are interested in studying hibernation/torpor because of the robust state of tolerance to constrained oxygen delivery, oligemia, and hypothermia achieved by the tissues of hibernating mammals. The role of the serine/threonine kinase Akt (also known as PKB) has been examined in torpor in previous studies. However, this is the first study that examines the level of Akt phosphorylation in the liver during the two transition phases of the hibernation cycle: entrance into torpor, and the subsequent arousal from torpor. Our results indicate that Akt is activated in the squirrel liver by phosphorylation of two key residues (Thr(308) and Ser(473)) during entrance into torpor and arousal from torpor. Moreover, we observed increased phosphorylation of key substrates of Akt during the two transition stages of torpor. Finally, this study reports the novel finding that PRAS40, a component of the TORC1 multi-protein complex and a potentially important modulator of metabolism, is regulated during torpor.
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PMID:Regulation of Akt during torpor in the hibernating ground squirrel, Ictidomys tridecemlineatus. 2035 31

Ischemic tolerance is as powerful and reproducible for neuro-protection as hypothermia. Several pathways could be involved in acquisition of ischemic tolerance. CREB is an abundant transcription factor in the brain and plays critical role on synaptic plasticity and neuronal survival. CREB activation has been also shown to be involved in ischemic tolerance. Ischemia or oxygen-glucose deprivation leads to release of glutamate, which binds to synaptic NMDA receptor. Then, influx of calcium ions into intracellular space activates calcium-calmodulin dependent protein kinase (CaMK). CaMK I/IV phosphorylates Ser 133 of CREB, and Thr 484 of salt-inducible kinase (SIK). Phosphorylation of SIK2 at Thr 484 triggers degradation of SIK2 through ubiquitin proteasome system. SIK2 maintains the phosphorylation level of CREB-regulated transcriptional co-activator (CRTC). Degradation of SIK2 induces dephosphorylation of CRTC1, and moves CRTC1 from cytoplasm into nucleus. Thus CRTC1 binds to basic ZIP domain of CREB. Both Ser133 phosphorylation and CRTC1 bound to the basic ZIP domain of CREB enhances CRE-mediated transcription, induces gene expression of survival factors, and renders the neurons resistant to subsequent severe ischemia.
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PMID:[CREB activation is a key player for ischemic tolerance in the brain]. 2319 62