Effects of hyperglycemia and hypercapnia on lipid metabolism during complete brain ischemia.
Ischemic damage is greatly enhanced by preischemic hyperglycemia or hypercapnia, which affects many intracellular responses including protein kinase C (PKC) translocation. We explored whether hyperglycemic or hypercapnic ischemia affects lipid metabolism, especially ischemia-induced release of free fatty acids (FFAs) and diacylglycerols (DAGs). A change in intraischemic level of acidosis was induced either by injecting glucose (hyperglycemic, HG) or by adding CO(2) (hypercapnic, HC). Complete cerebral ischemia was induced, and the brain was frozen in situ after 3, 5, and 10 min at 37 degrees C. Frontoparietal neocortex was dissected for FFA and DAG lipid analysis by thin-layer chromatography and gas-liquid chromatography. Significant differences were shown between normoglycemic and either hypercapnic or hyperglycemic values for individual and total FFAs. A significant delay in the release of FFA in ischemia with hyperglycemia or hypercapnia was observed. Significant differences were also shown in individual DAG-acyl groups and total DAGs. Hyperglycemic or hypercapnic ischemia resulted in a significant decrease of DAG at 10 min of ischemia. This was unexpected because a previous study showed that PKC translocation was significantly enhanced under similar condition at this time point. Upon cellular depolarization, massive influx of calcium and FFA accumulation may decrease the PKC dependence of DAG for translocation. In addition, PKC activation may lead to a negative feedback inhibition of phospholipase C.
Katsura
Ken-ichiro
K
The Second Department of Internal Medicine, Nippon Medical School, Bunkyo-Ku, Tokyo 113-8603, Japan. k-katsur@nms.ac.jp
Rodriguez de Turco
Elena B
EB
Siesjö
Bo K
BK
Bazan
Nicolas G
NG
D000138:Acidosis / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D006935:Hypercapnia / Q000150:complications / Q000378:metabolism*; D006943:Hyperglycemia / Q000150:complications / Q000378:metabolism*; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D004075:Diglycerides; D005230:Fatty Acids, Nonesterified; D011493:Protein Kinase C