Brain arachidonic acid cascade enzymes are upregulated in a rat model of unilateral Parkinson disease.
Arachidonic acid (AA) signaling is upregulated in the caudate-putamen and frontal cortex of unilaterally 6-hydroxydopamine (6-OHDA) lesioned rats, a model for asymmetrical Parkinson disease. AA signaling can be coupled to D(2)-like receptor initiated AA hydrolysis from phospholipids by cytosolic phospholipase A(2) (cPLA(2)) and subsequent metabolism by cyclooxygenase (COX)-2. In unilaterally 6-OHDA- and sham-lesioned rats, we measured brain expression of cPLA(2), other PLA(2) enzymes, and COX-2. Activity and protein levels of cPLA(2) were significantly higher as was COX-2-protein in caudate-putamen, frontal cortex and remaining brain on the lesioned compared to intact side of the 6-OHDA lesioned rats, and compared to sham brain. Secretory sPLA(2) and Ca(2+)-independent iPLA(2) expression did not differ between sides or groups. Thus, the tonically increased ipsilateral AA signal in the lesioned rat corresponds to upregulated cPLA(2) and COX-2 expression within the AA metabolic cascade, which may contribute to symptoms and pathology in Parkinson disease.
Lee
Ho-Joo
HJ
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
Bazinet
Richard P
RP
Rapoport
Stanley I
SI
Bhattacharjee
Abesh Kumar
AK
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology* / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000201:enzymology* / Q000378:metabolism; D054467:Phospholipases A2 / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D015854:Up-Regulation
D016718:Arachidonic Acid; D016627:Oxidopamine; D051546:Cyclooxygenase 2; D054467:Phospholipases A2