Glucosylceramide synthase activity and ceramide levels are modulated during cerebral ischemia after ischemic preconditioning.
After 24-hour middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats, brain ceramide level increased from baseline reached 595% (ischemic core) and 460% (perifocal/penumbral areas); brain glucosylceramide synthase (GCS) activities in these areas simultaneously decreased by 70% and 50%, respectively. Ten-minute MCAO preconditioning significantly attenuated 24-hour MCAO-induced ceramide accumulation by 40% to 60% in ischemic core and perifocal areas, and GCS activities improved by 60% to 70% in both areas. Thus, potentially toxic levels of brain ceramide induced by MCAO were attenuated to intermediate levels in preconditioned animals; brain GCS activity was relatively preserved. In ischemic tolerance, GCS appears to modulate otherwise high levels of brain ceramide.
Takahashi
Kenzo
K
Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Ginis
Irene
I
Nishioka
Ryoji
R
Klimanis
Dace
D
Barone
Frank C
FC
White
Raymond F
RF
Chen
Yong
Y
Hallenbeck
John M
JM
D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002518:Ceramides / Q000378:metabolism*; D005964:Glucosyltransferases / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery; D019194:Ischemic Preconditioning; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR
D002518:Ceramides; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase