To assess the biological consequences of superoxide dismutase 1 overproduction within cells, the human superoxide dismutase 1 gene and a human superoxide dismutase 1 cDNA were introduced into mouse L cells and NS20Y neuroblastoma cells.
Expression of a Cu,Zn superoxide dismutase typical of familial amyotrophic lateral sclerosis induces mitochondrial alteration and increase of cytosolic Ca2+ concentration in transfected neuroblastoma SH-SY5Y cells.
Proteolytic processing characteristic of caspase-1 activation is seen both in spinal cords of transgenic ALS mice and neurally differentiated neuroblastoma (line N2a) cells with SOD1 mutations.
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.
On the contrary, overexpression of mutant SOD1s associated with familial amyotrophic lateral sclerosis (FALS) impairs CN activity both in transfected human neuroblastoma cell lines and in the motor cortex of brain from FALS-transgenic mice.
It also appears that the Hsp-SOD1 complex recruits other proteins present in the neuroblastoma cell and presumably in motor neurons to form sedimentable aggregates.
In order to investigate the effect of various calcium modulators and the SOD-1 mutation on neuronal death, we tested motoneuron-neuroblastoma hybrid (VSC 4.1) cells constitutively expressing human SOD-1 gene with mutations (A4V, G93A) or wild-type.
In this paper, we report a calcineurin-dependent activation of nuclear factor-kappaB (NF-kappaB) induced by the expression of familial amyotrophic lateral sclerosis (fALS)-SOD1s in human neuroblastoma cell lines.
We demonstrated that expression of the fully active G93ACu,Zn superoxide dismutase mutant in neuroblastoma cells is associated with an increased level of oxidatively modified proteins, in terms of carbonylated residues.
We report that the expression of mutant G93A copper/zinc superoxide dismutase (SOD1), associated with familial amyotrophic lateral sclerosis, specifically causes a decrease in MTT reduction rate and ATP levels and an increase in both cytosolic and mitochondrial reactive oxygen species (ROS) production in human neuroblastoma SH-SY5Y cells compared to cells overexpressing wild-type SOD1 and untransfected cells.
Overexpression of Cu-Zn superoxide dismutase protects neuroblastoma cells against dopamine cytotoxicity accompanied by increase in their glutathione level.
We show that human glioblastoma cells expressing G93A-SOD1 induce activation of caspase-1, release of cytokines, and activation of apoptotic pathways in cocultured human neuroblastoma cells also expressing G93A-SOD1.
Impairment of glutamate transport and increased vulnerability to oxidative stress in neuroblastoma SH-SY5Y cells expressing a Cu,Zn superoxide dismutase typical of familial amyotrophic lateral sclerosis.
In order to investigate the role of Hsp27 in mutant SOD1-dependent cell death, we used mutant and wild type SOD1 overexpressing N2a mouse neuroblastoma cells.
In order to investigate the basis of the tissue specificity of mutant SOD1 we compared the effect of the continuous expression of wild-type or mutant (G93A) human SOD1 on mitochondrial morphology in the NSC-34 motoneuronal-like, the N18TG2 neuroblastoma and the non-neuronal Madin-Darby Canine Kidney (MDCK) cell lines.
Previously, we reported that overexpression of the mitochondrial antioxidant manganese superoxide dismutase (MnSOD or SOD2) attenuates cytotoxicity induced by expression of the G37R-SOD1 mutant in a human neuroblastoma cell culture model of ALS.
To understand better the role of these mutations in the pathophysiology of FALS we have compared the pattern of proteins expressed in human neuroblastoma SH-SY5Y cell line with those of cell lines transfected with plasmids expressing the wild-type human SOD1 and the H46R and G93A mutants.
In the light of the possibility that different SOD1 entities could be expressed also in other neurodegenerative disorders, as a sort of unifying event with AD and PD, we have investigated amyotrophic lateral sclerosis (ALS) using human neuroblastoma SH-SY5Y cells with mutated SOD1 gene H46R as cellular model.
SH-SY5Y neuroblastoma cells transfected with the G93A mutant of SOD1 typical for familial ALS (G93A-SOD1) were more vulnerable to the neurotoxic action of pneumolysin and to the attack of monocytes stimulated by Pam3CSK4 than SH-SY5Y cells transfected with wild-type human SOD1.