Preferential expression of superoxide dismutase messenger RNA in melanized neurons in human mesencephalon.
The copper-zinc-dependent superoxide dismutase messenger RNA expression was studied at cellular level by in situ hybridization, using a 35S-labelled complementary DNA probe homologous to human copper-zinc-dependent superoxide dismutase messenger RNA, in the dopaminergic neuron-containing areas of the human mesencephalon (the substantia nigra pars compacta, ventral tegmental area, central gray substance and peri- and retrorubral region corresponding to catecholaminergic cell group A8). The autoradiographic labelling signal was localized in neurons. No detectable hybridization signal could be found in the glial cells. Copper-zinc-dependent superoxide dismutase messenger RNA was detected in melanin-containing neurons as well as in non-melanized neurons. Quantification at cellular level, taking the autoradiographic silver grain density as an index of the abundance of copper-zinc-dependent superoxide dismutase messenger RNA, indicated that hybridization level was higher in the melanized than in the non-melanized neurons within a region. Among melanized neurons, cellular copper-zinc-dependent superoxide dismutase messenger RNA content was lowest in the neurons of the substantia nigra. No significant difference in levels of transcripts was evidenced between the groups of non-melanized neurons. The data suggest that the abundance of copper-zinc-dependent superoxide dismutase messenger RNA is higher in the mesencephalic neurons containing neuromelanin compared to other neurons. Thus, the melanized neurons have a particular defence system against oxygen toxicity, which may represent a basis for their preferential vulnerability to Parkinson's disease.
Zhang
P
P
INSERM U289, Hôpital de la Salpêtrière, Paris, France.
Damier
P
P
Hirsch
E C
EC
Agid
Y
Y
Ceballos-Picot
I
I
Sinet
P M
PM
Nicole
A
A
Laurent
M
M
Javoy-Agid
F
F
D000368:Aged; D000369:Aged, 80 and over; D015342:DNA Probes; D004298:Dopamine / Q000032:analysis; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008543:Melanins / Q000032:analysis*; D008636:Mesencephalon / Q000166:cytology / Q000201:enzymology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000201:enzymology*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D013378:Substantia Nigra / Q000166:cytology / Q000201:enzymology; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics
D015342:DNA Probes; D008543:Melanins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C014121:neuromelanin; D013482:Superoxide Dismutase; D004298:Dopamine