Abstract
Calcineurin (CN) is a protein phosphatase involved in a wide range of cellular responses to calcium-mobilizing signals, and a role for this enzyme in neuropathology has been postulated. We have investigated the possibility that redox modulation of CN activity is relevant to neuropathological conditions where an imbalance in reactive oxygen species has been described. We have monitored CN activity in cultured human neuroblastoma SH-SY5Y cells and obtained evidence that CN activity is promoted by treatment with ascorbate or dithiothreitol and impaired by oxidative stress. Evidence for the existence of a redox regulation of this enzyme has been also obtained by overexpression of wild-type antioxidant Cu,Zn superoxide dismutase (SOD1) that promotes CN activity and protects it from oxidative inactivation. 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. These data suggest that CN might be a target in the pathogenesis of SOD1-linked FALS.
| Original language | English |
|---|---|
| Pages (from-to) | 606-613 |
| Number of pages | 8 |
| Journal | Journal of Neurochemistry |
| Volume | 75 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2000 |
Fingerprint
Keywords
- Calcineurin
- Familial amyotrophic lateral sclerosis
- Neurodegeneration
- Reactive oxygen species
- Redox regulation
- Superoxide dismutase
ASJC Scopus subject areas
- Biochemistry
- Cellular and Molecular Neuroscience
Cite this
Calcineurin activity is regulated both by redox compounds and by mutant familial amyotrophic lateral sclerosis-superoxide dismutase. / Ferri, Alberto; Gabbianelli, Roberta; Casciati, Arianna; Paolucci, Egle; Rotilio, Giuseppe; Carrì, Maria Teresa.
In: Journal of Neurochemistry, Vol. 75, No. 2, 2000, p. 606-613.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Calcineurin activity is regulated both by redox compounds and by mutant familial amyotrophic lateral sclerosis-superoxide dismutase
AU - Ferri, Alberto
AU - Gabbianelli, Roberta
AU - Casciati, Arianna
AU - Paolucci, Egle
AU - Rotilio, Giuseppe
AU - Carrì, Maria Teresa
PY - 2000
Y1 - 2000
N2 - Calcineurin (CN) is a protein phosphatase involved in a wide range of cellular responses to calcium-mobilizing signals, and a role for this enzyme in neuropathology has been postulated. We have investigated the possibility that redox modulation of CN activity is relevant to neuropathological conditions where an imbalance in reactive oxygen species has been described. We have monitored CN activity in cultured human neuroblastoma SH-SY5Y cells and obtained evidence that CN activity is promoted by treatment with ascorbate or dithiothreitol and impaired by oxidative stress. Evidence for the existence of a redox regulation of this enzyme has been also obtained by overexpression of wild-type antioxidant Cu,Zn superoxide dismutase (SOD1) that promotes CN activity and protects it from oxidative inactivation. 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. These data suggest that CN might be a target in the pathogenesis of SOD1-linked FALS.
AB - Calcineurin (CN) is a protein phosphatase involved in a wide range of cellular responses to calcium-mobilizing signals, and a role for this enzyme in neuropathology has been postulated. We have investigated the possibility that redox modulation of CN activity is relevant to neuropathological conditions where an imbalance in reactive oxygen species has been described. We have monitored CN activity in cultured human neuroblastoma SH-SY5Y cells and obtained evidence that CN activity is promoted by treatment with ascorbate or dithiothreitol and impaired by oxidative stress. Evidence for the existence of a redox regulation of this enzyme has been also obtained by overexpression of wild-type antioxidant Cu,Zn superoxide dismutase (SOD1) that promotes CN activity and protects it from oxidative inactivation. 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. These data suggest that CN might be a target in the pathogenesis of SOD1-linked FALS.
KW - Calcineurin
KW - Familial amyotrophic lateral sclerosis
KW - Neurodegeneration
KW - Reactive oxygen species
KW - Redox regulation
KW - Superoxide dismutase
UR - http://www.scopus.com/inward/record.url?scp=0033914937&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033914937&partnerID=8YFLogxK
U2 - 10.1046/j.1471-4159.2000.0750606.x
DO - 10.1046/j.1471-4159.2000.0750606.x
M3 - Article
C2 - 10899935
AN - SCOPUS:0033914937
VL - 75
SP - 606
EP - 613
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 2
ER -