Subcellular distribution and autophosphorylation of calcium/calmodulin- dependent protein kinase II-α in rat hippocampus in a model of ischemic tolerance

TY - JOUR

T1 - Subcellular distribution and autophosphorylation of calcium/calmodulin- dependent protein kinase II-α in rat hippocampus in a model of ischemic tolerance

AU - Shamloo, M.

AU - Kamme, F.

AU - Wieloch, Tadeusz

PY - 2000/3

Y1 - 2000/3

N2 - A brief period of sublethal ischemia induces resistance to a subsequent, otherwise lethal, ischemic insult, a process named ischemic tolerance or preconditioning. A persistently disturbed cell signaling during reperfusion after cerebral ischemia has been proposed to contribute to ischemic cell death. Here, we report on the effect of ischemic preconditioning on the levels of the regulatory α-subunit of calcium/calmodulin protein kinase II and its phosphorylation in the hippocampal CA1 region. We found that during and following lethal cerebral ischemia, calcium/calmodulin protein kinase II- α is persistently translocated to cell membranes, where it becomes phosphorylated at threonine 286. In contrast, in the preconditioned brains the translocation and phosphorylation are transient and return to preischemic values after one day of reperfusion. At this time of reperfusion, the total level of calcium/calmodulin protein kinase II-α is significantly lower in preconditioned animals compared to the sham and non-conditioned animals. After one day of reperfusion, the level of calcium/calmodulin protein kinase II-α messenger RNA decreases in the non-conditioned brains, whereas it is unchanged in preconditioned brains. We conclude that, during and after ischemia, calcium/calmodulin protein kinase II-α is translocated to cell membranes and becomes phosphorylated at threonine 286. This could detrimentally influence cell survival by changing receptor function and ion channel conductance. Ischemic preconditioning prevents the persistent presence of calcium/calmodulin protein kinase II-α at cell membranes, presumably by enhancing its degradation, which could be part of a neuroprotective mechanism of ischemic tolerance. (C) 2000 IBRO.

AB - A brief period of sublethal ischemia induces resistance to a subsequent, otherwise lethal, ischemic insult, a process named ischemic tolerance or preconditioning. A persistently disturbed cell signaling during reperfusion after cerebral ischemia has been proposed to contribute to ischemic cell death. Here, we report on the effect of ischemic preconditioning on the levels of the regulatory α-subunit of calcium/calmodulin protein kinase II and its phosphorylation in the hippocampal CA1 region. We found that during and following lethal cerebral ischemia, calcium/calmodulin protein kinase II- α is persistently translocated to cell membranes, where it becomes phosphorylated at threonine 286. In contrast, in the preconditioned brains the translocation and phosphorylation are transient and return to preischemic values after one day of reperfusion. At this time of reperfusion, the total level of calcium/calmodulin protein kinase II-α is significantly lower in preconditioned animals compared to the sham and non-conditioned animals. After one day of reperfusion, the level of calcium/calmodulin protein kinase II-α messenger RNA decreases in the non-conditioned brains, whereas it is unchanged in preconditioned brains. We conclude that, during and after ischemia, calcium/calmodulin protein kinase II-α is translocated to cell membranes and becomes phosphorylated at threonine 286. This could detrimentally influence cell survival by changing receptor function and ion channel conductance. Ischemic preconditioning prevents the persistent presence of calcium/calmodulin protein kinase II-α at cell membranes, presumably by enhancing its degradation, which could be part of a neuroprotective mechanism of ischemic tolerance. (C) 2000 IBRO.

KW - Brain ischemia

KW - Calcium/calmodulin-dependent protein kinase II

KW - Cell death

KW - Phosphorylation

KW - Tolerance

UR - http://www.scopus.com/inward/record.url?scp=0034112048&partnerID=8YFLogxK

U2 - 10.1016/S0306-4522(99)00586-2

DO - 10.1016/S0306-4522(99)00586-2

M3 - Article

C2 - 10727785

AN - SCOPUS:0034112048

VL - 96

SP - 665

EP - 674

JO - Neuroscience

JF - Neuroscience

SN - 1873-7544

IS - 4

ER -