Increased myocardial N-myristoyltransferase activity in rotenone model of Parkinsonism.
There is widespread brain pathology in Parkinson's disease (PD), with the primary pathology in the substantia nigra. Oxidative stress is believed to play a role in cell death in PD. Rotenone is a mitochondrial toxin which can produce Parkinson syndrome (PS) in rats. Myristoyl-CoA:protein N-myristoyltransferase (NMT), which catalyzes the co-translational transfer of myristate from myristoyl-CoA to the amino-terminal glycine residue of selected polypeptides, is increased in the myocardium of ischemia-reperfusion rat model myocardium. Animals received rotoneone (n=10) or placebo vehicle (n=6) via Alzet osmotic pumps. Mean cardiac muscle NMT activity of placebo treated (control) rats was 0.608+/-0.366 units/mg protein. Rats with mild or no detectable PS features on rotenone showed slight (mean 0.853+/-0.192) but insignificantly increased activity. Rats that had moderately severe PS features had higher level of NMT activity (mean 1.223+/-0.057), which was borderline significant compared to controls (P=0.066). Rats with severe PS features had the highest NMT activity (1.353+/-0.128) which was significantly greater compared to controls (P=0.003) and to the rats that had equivocal or no motor slowing (P=0.005). Our data show cardiac metabolic dysfunction in a rotenone rat model of PS. The severity of this change correlates with the severity of motor manifestations. Further studies of NMT activity in human PD cases and patients with cardiomyopathy of unknown cause may provide valuable information in these disorders.
Pasha
Mohammed Khysar
MK
Division of Neurology, College of Medicine, Royal University Hospital, University of Saskatchewan, Saskatoon, Canada.
Sharma
Rajendra K
RK
Rajput
Alexander H
AH
D000214:Acyl Coenzyme A / Q000378:metabolism*; D000628:Aminophylline / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000378:metabolism*; D004195:Disease Models, Animal; D004338:Drug Combinations; D006801:Humans; D008297:Male; D005996:Nitroglycerin / Q000378:metabolism*; D010208:Papaverine / Q000378:metabolism*; D010300:Parkinson Disease / Q000201:enzymology*; D010634:Phenobarbital / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D012402:Rotenone / Q000494:pharmacology*
D000214:Acyl Coenzyme A; D004338:Drug Combinations; C026863:Myocardon; D012402:Rotenone; D000628:Aminophylline; C040349:S-tetradecanoyl-coenzyme A; D001285:Atropine; D010208:Papaverine; D005996:Nitroglycerin; D010634:Phenobarbital