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 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 NF--ÛB induced by the expression of fALS-SOD1s in human neuroblastoma cell lines. Alteration of the phosphorylation state of I-ÛB-Ñ-n-n-vthe inhibitor of NF--ÛB 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 signalling pathways involved in the pathogenesis of fALS.
Oxidative modulation of NF-?[B in human cells expressing mutant FALS-typical superoxide dismutases
Ferri A;
2002
Abstract
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 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 NF--ÛB induced by the expression of fALS-SOD1s in human neuroblastoma cell lines. Alteration of the phosphorylation state of I-ÛB-Ñ-n-n-vthe inhibitor of NF--ÛB 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 signalling pathways involved in the pathogenesis of fALS.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
