Antioxidant status alters levels of Fas-associated death domain-like IL-1B-converting enzyme inhibitory protein following neonatal hypoxia-ischemia

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Antioxidant status alters levels of Fas-associated death domain-like IL-1B-converting enzyme inhibitory protein following neonatal hypoxia-ischemia

Payton, K. S. (author)

Sheldon, R. A. (author)

Mack, D. W. (author)

Zhu, Changlian, 1964 (author): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation

Blomgren, Klas, 1963 (author): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institutionen för kliniska vetenskaper,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation,Institute of Clinical Sciences

Ferriero, D. M. (author)

Northington, F. J. (author)

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(creator_code:org_t)

2007
2007
English.
In: Dev Neurosci. - 1421-9859. ; 29:4-5, s. 403-11

Related links:: https://gup.ub.gu.se...

Journal article (peer-reviewed)

Abstract Subject headings

Activation of Fas death receptor (Fas DR) signaling cascade is seen after neonatal hypoxia-ischemia (HI). Cell survival is favored when signaling through the death-inducing signaling complex and cleavage of caspase 8 to its active form is blocked by FLIP, a dominant negative of caspase 8. H2O2 quickly downregulates expression of FLIP. Neonatal mice overexpressing glutathione peroxidase (GPx) have less injury and less H2O2 accumulation compared with neonatal mice overexpressing superoxide dismutase (SOD) or wild-type (WT) littermates. Expression of both FLIP(L) and FLIP(S) is increased in GPx-oxerexpressing mice relative to WT mice at 24 h and relative to SOD-overexpressing mice at 2 and 24 h following neonatal HI (ANOVA, p < 0.05). There is an increase in Fas DR expression at 24 h in both WT and GPx-overexpressing mice and significant differences between WT and SOD-overexpressing mice (ANOVA, p < 0.01). There is no difference in FADD expression among the 3 groups 24 h after HI. At 24 h following HI, the ratio of FLIP to Fas DR expression supports a significant negative correlation with injury score (r2 = 0.99, slope = -4.01), and expression of both the active fragment of caspase 8 and caspase 8 activity is increased in SOD overexpressors compared to GPx overexpressors at 24 h after HI (ANOVA, p < 0.05). The overall degree of injury previously seen in these 3 strains correlates well with changes in expression of Fas DR signaling proteins favoring neuroprotection in the GPx-overexpressing mice, i.e. increased FLIP expression and decreased caspase 8 activity compared to SODtg mice. The mechanism by which antioxidant status alters FLIP levels following neonatal HI may be related to the ability to detoxify H2O2 produced following neonatal HI.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)

Keyword

Animals
Animals
Newborn
Antigens
CD95/*metabolism
Antioxidants/*metabolism
Birth Injuries/*metabolism/physiopathology
Brain/metabolism/physiopathology
CASP8 and FADD-Like Apoptosis Regulating Protein/*metabolism
Caspase 8/metabolism
Cell Death/physiology
Cell Survival/physiology
Disease Models
Animal
Fas-Associated Death Domain Protein/metabolism
Glutathione Peroxidase/metabolism
Humans
Hydrogen Peroxide/metabolism
Hypoxia-Ischemia
Brain/*metabolism/physiopathology
Mice
Mice
Transgenic
Oxidative Stress/*physiology
Superoxide Dismutase/metabolism

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ref (subject category)
art (subject category)

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By the author/editor: Payton, K. S.; Sheldon, R. A.; Mack, D. W.; Zhu, Changlian, ...; Blomgren, Klas, ...; Ferriero, D. M.; show more...; Northington, F. ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Physiology

Articles in the publication: Dev Neurosci

By the university: University of Gothenburg

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