Rapid tau protein dephosphorylation and differential rephosphorylation during cardiac arrest-induced cerebral ischemia and reperfusion.
The effects of cerebral ischemia/reperfusion on phosphorylation of microtubule-associated tau proteins were assessed in a canine model of cardiac arrest. As tau proteins are phosphorylated by kinases involved in different transduction signal pathways, their phosphorylation state is an excellent marker of neuronal homeostasis and microtubule dynamics. Canine brain tau proteins were characterized by immunoblotting using phosphorylation-dependent antibodies and antisera raised against different amino- and carboxy-terminal tau sequences. The present study reports a complete dephosphorylation of tau proteins during ischemia, which is shown by a higher electrophoretic mobility and the almost (if not total) disappearance of phosphorylation-dependent monoclonal antibody labeling. After 2-hour restoration of spontaneous circulation, a decrease in the electrophoretic mobility was observed, and after 24 hours of reperfusion, a full restoration of the phosphorylation was visualized using phosphorylation-dependent monoclonal antibodies directed against Ser/Thr-Pro sites. However, one particular phosphorylation site involved in tau binding to microtubules, located on Ser262/356, was never fully significantly rephosphorylated, suggesting that microtubule metabolism was still affected after 24 hours of reperfusion. Thus, the sequential and differential recovery of tau phosphorylation after ischemia followed by reperfusion is a useful marker with which to monitor neuronal integrity after brain ischemia.
Mailliot
C
C
INSERM U422, Lille, France.
Podevin-Dimster
V
V
Rosenthal
R E
RE
Sergeant
N
N
Delacourte
A
A
Fiskum
G
G
Buée
L
L
D000818:Animals; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000209:etiology*; D019556:COS Cells; D002540:Cerebral Cortex / Q000378:metabolism; D004285:Dogs; D005260:Female; D006323:Heart Arrest / Q000150:complications*; D006801:Humans; D015151:Immunoblotting; D010766:Phosphorylation; D015427:Reperfusion Injury / Q000378:metabolism*; D013997:Time Factors; D016875:tau Proteins / Q000378:metabolism*
D016875:tau Proteins