Molecular responses to acidosis of central chemosensitive neurons in brain.
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.
Shimokawa
Noriaki
N
Department of Integrative Physiology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi-shi 371-8511, Japan. simokawa@med.gunma-u.ac.jp
Dikic
Ivan
I
Sugama
Shuei
S
Koibuchi
Noriyuki
N
D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006935:Hypercapnia / Q000378:metabolism; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis / Q000235:genetics; D009185:Myelin Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D051257:Proto-Oncogene Proteins c-maf; D015398:Signal Transduction
D004268:DNA-Binding Proteins; C484161:Gpm6b protein, rat; C495607:MAF protein, human; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D051257:Proto-Oncogene Proteins c-maf; C468273:Slc45a1 protein, rat