Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10817107 | Cellular Signalling | 2005 | 10 Pages |
Abstract
Significant advances have been made in understanding how neurons sense and respond to acidosis at the cellular level. Decrease in pH of the cerebrospinal fluid followed by hypercapnia (increased arterial CO2) is monitored by the chemosensory neurons of the medulla oblongata. Then the intracellular signalling pathways are activated to regulate specific gene expression, which leads to a hyperventilatory response. However, little is known about molecular details of such cellular responses. Recent studies have identified several transcription factors such as c-Jun, Fos and small Maf proteins that may play critical roles in the brain adaptation to hypercapnia. Hypercapnic stimulation also activates c-Jun NH2-terminal kinase (JNK) cascade via influx of extracellular Ca2+ through voltage-gated Ca2+ channels. In addition, several transmembrane proteins including Rhombex-29 (rhombencephalic expression protein-29 kDa) and Past-A (proton-associated sugar transporter-A) have been implicated in regulation of H+ sensitivity and brain acidosis-mediated energy metabolism, respectively. This review discusses current knowledge on the signalling mechanisms and molecular basis of neuronal adaptation during acidosis.
Keywords
CREOvarian cancer G-protein-coupled receptor 1OGR1Ca2+/CaMATF-2Phospholipase C-βc-Jun NH2-terminal kinaseGLUTASICinositol triphosphatePKCJnkAP-1IP3ERKVMSPLCβbZIPCa2+/calmodulinGlucose transporterbasic leucine zipperVentral medullary surfaceDifferential displaycyclic AMP response elementNuclear transcription factoractivating transcription factor-2mapGlucose homeostasismitogen-activated proteinactivator protein 1Protein kinase CCa2+ channelsextracellular signal-regulated kinase
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Authors
Noriaki Shimokawa, Ivan Dikic, Shuei Sugama, Noriyuki Koibuchi,