Modifications of apoptosis-related protein levels in lymphocytes of patients with Parkinson's disease. The effect of dopaminergic treatment.
In this study, we investigated whether changes in the regulatory mechanisms of apoptosis and oxidative stress may be detected, peripherally, in patients with Parkinson's disease (PD). For this purpose, we measured caspase-3 activity, Bcl-2 concentrations, peripheral benzodiazepine receptor (PBR) expression and Cu/Zn superoxide dismutase (SOD) concentrations in lymphocytes of untreated PD patients, patients treated only with L-Dopa or with L-Dopa and dopamine agonists and healthy volunteers. Caspase-3 activity was significantly increased in all PD patient groups. Patients treated with L-Dopa and dopamine agonists showed the lowest values of Bcl-2, coupled with the highest density of PBRs, while increased levels of Cu/Zn SOD were found in the group under monotherapy with L-Dopa. We also found, in PD patients, clear, negative correlations between Bcl-2 levels and both duration and severity of the disease. Our findings point to the existence of changes in the regulatory mechanisms of apoptosis in PD patients -- observable outside the central nervous system -- which seem to be modulated by the pharmacological treatment with dopaminergic agents.
Blandini
F
F
Laboratory of Functional Neurochemistry, Neurological Institute C. Mondino, Pavia, Italy. fabio.blandini@mondino.it
Cosentino
M
M
Mangiagalli
A
A
Marino
F
F
Samuele
A
A
Rasini
E
E
Fancellu
R
R
Tassorelli
C
C
Pacchetti
C
C
Martignoni
E
E
Riboldazzi
G
G
Calandrella
D
D
Lecchini
S
S
Frigo
G
G
Nappi
G
G
D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D018450:Disease Progression; D015259:Dopamine Agents / Q000627:therapeutic use*; D018491:Dopamine Agonists / Q000494:pharmacology; D005260:Female; D006801:Humans; D007980:Levodopa / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism*; D017933:Peripheral Nervous System / Q000187:drug effects / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D000978:Antiparkinson Agents; D015259:Dopamine Agents; D018491:Dopamine Agonists; D019253:Proto-Oncogene Proteins c-bcl-2; D011963:Receptors, GABA-A; D007980:Levodopa; D013482:Superoxide Dismutase; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases