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TNF-related apoptosis-inducing ligand (TRAIL) signaling and cell death in the immature central nervous system after hypoxia-ischemia and inflammation.

Kichev, Anton (author)
Rousset, Catherine I (author)
Baburamani, Ana A (author)
Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi,Institutionen för neurovetenskap och fysiologi,Institute of Clinical Sciences, Department of Obstetrics and Gynecology,Institute of Neuroscience and Physiology
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Levison, Steven W (author)
Wood, Teresa L (author)
Gressens, Pierre (author)
Thornton, Claire (author)
Hagberg, Henrik, 1955 (author)
Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi,Institute of Neuroscience and Physiology,Institute of Clinical Sciences, Department of Obstetrics and Gynecology
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 (creator_code:org_t)
2014
2014
English.
In: The Journal of biological chemistry. - 1083-351X. ; 289:13, s. 9430-39
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Tumor Necrosis Factor Related Apoptosis-Inducing Ligand (TRAIL) is a member of the TNF family. The interaction of TRAIL with death receptor 4 (DR4) and DR5 can trigger apoptotic cell death. The aim of this study was to investigate the role of TRAIL signaling in neonatal hypoxia-ischemia (HI). Using a neonatal mouse model of HI, mRNA and protein expression of TRAIL, DR5 and the TRAIL decoy receptors osteoprotegerin (OPG), mDcTRAILR1 and mDcTRAILR2 were determined. In vitro, mRNA expression of these genes was measured in primary neurons and oligodendrocyte progenitor cells (OPCs) after inflammatory cytokine (TNF-α/IFN-γ) treatment and/or oxygen and glucose deprivation (OGD). The toxicity of these various paradigms was also measured. The expression of TRAIL, DR5, OPG and mDcTRAILR2 was significantly increased after HI. In vitro, inflammatory cytokines and OGD treatment significantly induced mRNAs for TRAIL, DR5, OPG and mDcTRAILR2 in primary neurons, and of TRAIL and OPG in OPCs. TRAIL protein was expressed primarily in microglia and astroglia whereas DR5 co-localized with neurons and OPCs in vivo. OGD enhanced TNF-α/IFN-γ toxicity in both neuronal and OPC cultures. Recombinant TRAIL exerted toxicity alone or in combination with OGD and TNF-α/IFN-γ in primary neurons but not in OPC cultures. The marked increases in the expression of TRAIL and its receptors after cytokine exposure and OGD in primary neurons and OPCs were similar to those found in our animal model of neonatal HI. The toxicity of TRAIL in primary neurons suggests that TRAIL signaling participates in neonatal brain injury after inflammation and HI.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Pediatrik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Pediatrics (hsv//eng)

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