TY - JOUR
T1 - Oxidative modulation of nuclear factor-κB in human cells expressing mutant fALS-typical superoxide dismutases
AU - Casciati, Arianna
AU - Ferri, Alberto
AU - Cozzolino, Mauro
AU - Celsi, Fulvio
AU - Nencini, Monica
AU - Rotilio, Giuseppe
AU - Carrì, Maria Teresa
PY - 2002/12
Y1 - 2002/12
N2 - Previous evidence supports the notion of a redox regulation of protein phosphatase calcineurin that might be relevant for neurodegenerative processes where an imbalance between generation and removal of reactive oxygen species occurs. We have recently observed that calcineurin activity is depressed in human neuroblastoma cells expressing Cu,Zn superoxide dismutase (SOD1) mutant G93A and in brain areas from G93A transgenic mice, and that mutant G93A-SOD1 oxidatively inactivates calcineurin in vitro. We have studied the possibility that, by interfering directly with calcineurin activity, mutant SOD1 can modulate pathways of signal transduction mediated by redox-sensitive transcription factors. In this paper, we report a calcineurin-dependent activation of nuclear factor-κB (NF-κB) induced by the expression of familial amyotrophic lateral sclerosis (fALS)-SOD1s in human neuroblastoma cell lines. Alteration of the phosphorylation state of IκBα (the inhibitor of NF-κB translocation into the nucleus) and induction of cyclooxygenase 2 are consistent with the up-regulation of this transcription factor in this system. All of these modifications might be relevant to signaling pathways involved in the pathogenesis of fALS.
AB - Previous evidence supports the notion of a redox regulation of protein phosphatase calcineurin that might be relevant for neurodegenerative processes where an imbalance between generation and removal of reactive oxygen species occurs. We have recently observed that calcineurin activity is depressed in human neuroblastoma cells expressing Cu,Zn superoxide dismutase (SOD1) mutant G93A and in brain areas from G93A transgenic mice, and that mutant G93A-SOD1 oxidatively inactivates calcineurin in vitro. We have studied the possibility that, by interfering directly with calcineurin activity, mutant SOD1 can modulate pathways of signal transduction mediated by redox-sensitive transcription factors. In this paper, we report a calcineurin-dependent activation of nuclear factor-κB (NF-κB) induced by the expression of familial amyotrophic lateral sclerosis (fALS)-SOD1s in human neuroblastoma cell lines. Alteration of the phosphorylation state of IκBα (the inhibitor of NF-κB translocation into the nucleus) and induction of cyclooxygenase 2 are consistent with the up-regulation of this transcription factor in this system. All of these modifications might be relevant to signaling pathways involved in the pathogenesis of fALS.
KW - Calcineurin
KW - Familial amyotrophic lateral sclerosis
KW - IκBα
KW - Nuclear factor-κB
KW - Superoxide dismutase
KW - Tumor necrosis factor-α
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UR - http://www.scopus.com/inward/citedby.url?scp=0036892743&partnerID=8YFLogxK
U2 - 10.1046/j.1471-4159.2002.01232.x
DO - 10.1046/j.1471-4159.2002.01232.x
M3 - Article
C2 - 12437573
AN - SCOPUS:0036892743
VL - 83
SP - 1019
EP - 1029
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 5
ER -