TY - JOUR
T1 - Aberrant copper chemistry as a major mediator of oxidative stress in a human cellular model of amyotrophic lateral sclerosis
AU - Gabbianelli, Roberta
AU - Ferri, Alberto
AU - Rotilio, Giuseppe
AU - Carrì, Maria Teresa
PY - 1999
Y1 - 1999
N2 - We have investigated the response to oxidative stress in a model system obtained by stable transfection of the human neuroblastoma cell line SH-SY5Y with plasmids directing constitutive expression of either wild-type human Cu,Zn superoxide dismutase or a mutant of this enzyme (H46R) associated with familial amyotrophic lateral sclerosis. We report that expression of mutant H46R Cu,Zn superoxide dismutase induces a selective increase in paraquat sensitivity that is reverted by addition of D-penicillamine. Furthermore, expression of this mutant enzyme affects the activity of the endogenous wild- type enzyme both in basal conditions and in copper overloading experiments. Our data indicate that aberrant metal chemistry of this mutant enzyme is the actual mediator of oxidative stress and that concurrent impairment of the activity of wild-type endogenous enzyme compromises the cell's ability to respond to oxidative stress.
AB - We have investigated the response to oxidative stress in a model system obtained by stable transfection of the human neuroblastoma cell line SH-SY5Y with plasmids directing constitutive expression of either wild-type human Cu,Zn superoxide dismutase or a mutant of this enzyme (H46R) associated with familial amyotrophic lateral sclerosis. We report that expression of mutant H46R Cu,Zn superoxide dismutase induces a selective increase in paraquat sensitivity that is reverted by addition of D-penicillamine. Furthermore, expression of this mutant enzyme affects the activity of the endogenous wild- type enzyme both in basal conditions and in copper overloading experiments. Our data indicate that aberrant metal chemistry of this mutant enzyme is the actual mediator of oxidative stress and that concurrent impairment of the activity of wild-type endogenous enzyme compromises the cell's ability to respond to oxidative stress.
KW - Amyotrophic lateral sclerosis
KW - Copper
KW - D-Penicillamine
KW - Oxidative stress
KW - Paraquat
KW - Superoxide dismutase
UR - http://www.scopus.com/inward/record.url?scp=0032840228&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032840228&partnerID=8YFLogxK
U2 - 10.1046/j.1471-4159.1999.0731175.x
DO - 10.1046/j.1471-4159.1999.0731175.x
M3 - Article
C2 - 10461909
AN - SCOPUS:0032840228
VL - 73
SP - 1175
EP - 1180
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 3
ER -