Prostaglandin H(2)-derived adducts of proteins correlate with Alzheimer's disease severity.
The formation of cyclooxygenase-derived lipid adducts of protein in brains of patients who had Alzheimer's disease has been investigated. The enzymatic product of the cyclooxygenases, prostaglandin H2, rearranges in part to highly reactive gamma-ketoaldehydes, levuglandin (LG) E(2) and LGD(2). These gamma-ketoaldehydes react with free amines on proteins to yield a covalent adduct. Utilizing analysis of the levuglandinyl-lysine adducts by liquid chromatography-tandem mass spectrometry, we now find that this post-translational modification is increased significantly in the hippocampus in Alzheimer's disease. The magnitude of the increase correlates with the pathological evidence of severity.
Zagol-Ikapitte
Irene
I
Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.
Masterson
Tina S
TS
Amarnath
V
V
Montine
Thomas J
TJ
Andreasson
Katrin I
KI
Boutaud
Olivier
O
Oates
John A
JA
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D016022:Case-Control Studies; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007769:Lactams / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D044262:Prostaglandin H2 / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism; D012720:Severity of Illness Index
D007769:Lactams; D009419:Nerve Tissue Proteins; D011458:Prostaglandins E; D044262:Prostaglandin H2; C047684:levuglandin E2; D008239:Lysine