Acidosis enhances translocation of protein kinase C but not Ca(2+)/calmodulin-dependent protein kinase II to cell membranes during complete cerebral ischemia.
Systemic hyperglycemia and hypercapnia severely aggravate ischemic brain damage when instituted prior to cerebral ischemia. An aberrant cell signaling following ischemia has been proposed to be involved in ischemic cell death, affecting protein kinase C (PKC) and the calcium calmodulin kinase II (CaMKII). Using a cardiac arrest model of global brain ischemia of 10 min duration, we investigated the effect of hyperglycemia (20 mM) and hypercapnia (pCO(2) 300 mmHg) on the subcellular redistribution of PKC (alpha, beta, gamma) and CaMKII to synaptic membranes and to the microsomes, as well as the effect on PKC activity. We confirmed the marked translocation of PKC and CaMKII to cell membranes induced by ischemia, concomitantly with a decrease in the PKC activity in both the membrane fraction and cytosol. Hyperglycemia and hypercapnia markedly enhanced the translocation of PKC-gamma to cell membranes while other PKC isoforms were less affected. There was no effect of acidosis on PKC activity, or on translocation of CaMKII to cell membranes. Our data strongly suggest that the enhanced translocation of PKC to cell membranes induced by hyperglycemia and hypercapnia may contribute to the detrimental effect of tissue acidosis on the outcome following ischemia.
Katsura
K
K
The Second Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
Kurihara
J
J
Siesjö
B K
BK
Wieloch
T
T
D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002245:Carbon Dioxide / Q000097:blood; D002462:Cell Membrane / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D006323:Heart Arrest; D006943:Hyperglycemia / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D019579:Neocortex / Q000378:metabolism*; D010100:Oxygen / Q000097:blood; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000378:metabolism; D013997:Time Factors
D002245:Carbon Dioxide; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010100:Oxygen