Hypothermia Prevents the Ischemia‐Induced Translocation and Inhibition of Protein Kinase C in the Rat Striatum

Abstract

: The effect of hypothermia on the ischemia-induced changes in the subcellular distribution of protein kinase C (PKC)(γ), -(β_II), and -(α) and the activity of PKC was studied in striatal homogenates of rats subjected to 20 min of cerebral ischemia. The effect of post-ischemic cooling was also studied. During normothermic ischemia, PKC(γ) and -(β_II) increased 3.9-and 2.9-fold, respectively, in the particulate fraction, signifying a translocation of PKC to cell membranes. The levels of PKC(α) did not change significantly. PKC activity decreased during ischemia by 52% and 47% (p < 0.05) in the paniculate and cytosolic fractions, respectively, and remained inhibited for the 1 h recovery period. In hypothermic animals, there was no evidence of translocation, and the inhibition of PKC activity was completely abolished. Hypothermia induced in the recovery phase, however, did not affect PKC distribution or activity. The protective effect of intraischemic hypothermia may in part be due to the prevention of the ischemia-induced translocation and subsequent downregulation of PKC, possibly through a temperature-dependent modification of the cell membranes.