Isoflurane inhibits protein kinase Cgamma and calcium/calmodulin dependent protein kinase ii-alpha translocation to synaptic membranes in ischemic mice brains.
Volatile anesthetics isoflurane possibly improves the ischemic brain injury. However, its molecular actions are still unclear. In ischemia, protein kinase C (PKC)gamma and calcium/calmodulin dependent protein kinase II (CaMKII)-alpha are persistently translocated from cytosol to cell membranes, and diminish these translocation suggested to be neuroprotective. We thus tested a hypothesis that isoflurane inhibits PKCgamma and CaMKII-alpha translocation after ischemic brain insults. C57Bl/6J male mice were made to inhale 1 or 2 MAC isoflurane, after which 3 or 5 min cerebral ischemia was induced by decapitation. The sampled cerebrum cortex was then homogenized and centrifuged into crude synaptosomal fractions (P2), cytosolic fractions (S3), and particulate fractions (P3). CaMKII-alpha and PKCgamma levels of these fractions were analyzed by immunoblotting. PKCgamma and CaMKII-alpha are translocated to synaptic membrane from cytosol by cerebral ischemia, although isoflurane significantly inhibited such translocation. These results may explain in part the cellular and molecular mechanisms of neuroprotective effects of isoflurane.
Matsumoto
Shohei
S
Department of Anesthesiology, Tokyo Medical University Hospital, Nishishinjuku 6-7-1, Shinjuku-ku, Tokyo, 160-0023, Japan. shohei@tokyo-med.ac.jp
Murozono
Michihiro
M
Nagaoka
Daisuke
D
Matsuoka
Shuhei
S
Takeda
Akiko
A
Narita
Hideyuki
H
Watanabe
Seigo
S
Isshiki
Atsushi
A
Watanabe
Yasuo
Y
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D021381:Protein Transport; D013570:Synaptic Membranes / Q000187:drug effects* / Q000201:enzymology
D018685:Anesthetics, Inhalation; D007530:Isoflurane; C087857:protein kinase C gamma; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2