Expression of the HFE allelic variant H63D in SH-SY5Y cells affects tau phosphorylation at serine residues

Eric C. Hall, Sang Lee, Nootchanat Mairuae, Zachary Simmons, James Connor

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

A number of genetic association studies have appeared that address HFE gene variants in neurodegenerative disorders. However, the cellular impact of HFE in the nervous system has received little attention. To begin to address the role of the HFE allelic variants on cellular events associated with neurodegeneration, we examined the hypothesis that HFE polymorphisms are associated with alterations in tau phosphorylation in a human neuroblastoma cell line (SH-SY5Y). The results show that in a cell culture model, the H63D allele is associated with increased tau phosphorylation. The mechanisms responsible for these changes appear related to increased glycogen synthase kinase (GSK)-3β activity. GSK-3β activity is up-regulated in the cells expressing H63D HFE and can be modified by the addition of iron or treatment with an iron chelator in SH-SY5Y cells expressing wild-type HFE. Oxidative stress, also associated with elevated cellular iron, is associated with increased tau phosphorylation at the same sites as seen in H63D cells and treatment with Trolox, an anti-oxidant, lowered tau phosphorylation. These results suggest H63D HFE increases tau phosphorylation via GSK-3β activity and iron-mediated oxidative stress.

Original languageEnglish (US)
Pages (from-to)1409-1419
Number of pages11
JournalNeurobiology of Aging
Volume32
Issue number8
DOIs
StatePublished - Aug 1 2011

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Serine
Glycogen Synthase Kinase 3
Phosphorylation
Iron
Oxidative Stress
Genetic Association Studies
Chelating Agents
Neuroblastoma
Oxidants
Neurodegenerative Diseases
Nervous System
Cell Culture Techniques
Alleles
Cell Line
Genes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

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abstract = "A number of genetic association studies have appeared that address HFE gene variants in neurodegenerative disorders. However, the cellular impact of HFE in the nervous system has received little attention. To begin to address the role of the HFE allelic variants on cellular events associated with neurodegeneration, we examined the hypothesis that HFE polymorphisms are associated with alterations in tau phosphorylation in a human neuroblastoma cell line (SH-SY5Y). The results show that in a cell culture model, the H63D allele is associated with increased tau phosphorylation. The mechanisms responsible for these changes appear related to increased glycogen synthase kinase (GSK)-3β activity. GSK-3β activity is up-regulated in the cells expressing H63D HFE and can be modified by the addition of iron or treatment with an iron chelator in SH-SY5Y cells expressing wild-type HFE. Oxidative stress, also associated with elevated cellular iron, is associated with increased tau phosphorylation at the same sites as seen in H63D cells and treatment with Trolox, an anti-oxidant, lowered tau phosphorylation. These results suggest H63D HFE increases tau phosphorylation via GSK-3β activity and iron-mediated oxidative stress.",
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Expression of the HFE allelic variant H63D in SH-SY5Y cells affects tau phosphorylation at serine residues. / Hall, Eric C.; Lee, Sang; Mairuae, Nootchanat; Simmons, Zachary; Connor, James.

In: Neurobiology of Aging, Vol. 32, No. 8, 01.08.2011, p. 1409-1419.

Research output: Contribution to journalArticle

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