title: Glucosylceramide synthase activity and ceramide levels are modulated during cerebral ischemia after ischemic preconditioning.
abstract: 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.
authors.affiliation: Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Kenzo
authors.initials: K
authors.lastname: Takahashi
authors.forename: Irene
authors.initials: I
authors.lastname: Ginis
authors.forename: Ryoji
authors.initials: R
authors.lastname: Nishioka
authors.forename: Dace
authors.initials: D
authors.lastname: Klimanis
authors.forename: Frank C
authors.initials: FC
authors.lastname: Barone
authors.forename: Raymond F
authors.initials: RF
authors.lastname: White
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: John M
authors.initials: JM
authors.lastname: Hallenbeck
mesh_terms: 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
chemical_list: D002518:Ceramides; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase