Halothane binding proteome in human brain cortex.
Inhaled anesthetics bind specifically to a wide variety of proteins in the brain. This set of proteins must include those that contribute to the physiological and behavioral phenotypes of anesthesia and the related side effects. To identify the anesthetic-binding targets and functional pathways associated with these targets in human brain, halothane photolabeling and two-dimensional (2D) gel electrophoresis were used. Both membrane and soluble proteins from human temporal cortex were prepared. More than 300 membrane and 400 soluble protein spots were detected on the stained blots, of which 23 membrane and 34 soluble proteins were labeled by halothane and identified by mass spectroscopy. Their functional classification reveals five groups, including carbohydrate metabolism, protein folding, oxidative phosphorylation, nucleoside triphosphatase, and dimer/kinase activity with different correlative stringency. When network analysis of the interaction between these protein molecules is used, the weighted interaction accentuates the cellular protein components important in cell growth and proliferation, cell cycle and cell death, and cell-cell signaling and interactions, although no pathway was specific. This study provides evidence for multiple anesthetic binding targets and suggests potential pathways involved in their actions.
Pan
Jonathan Z
JZ
Department of Anesthesiology and Critical Care, University of Pennsylvania Health System, 3620 Hamilton Walk, Philadelphia, PA 19104, USA. jonathan.pan@uphs.upenn.edu
Xi
Jin
J
Tobias
John W
JW
Eckenhoff
Maryellen F
MF
Eckenhoff
Roderic G
RG
D002540:Cerebral Cortex / Q000737:chemistry* / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D004798:Enzymes / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D006221:Halothane / Q000378:metabolism*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000145:classification / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding; D020543:Proteome
D004798:Enzymes; D009419:Nerve Tissue Proteins; D020543:Proteome; D006221:Halothane