Involvement of extracellular signal-regulated kinases 1/2 and (phosphoinositide 3-kinase)/Akt signal pathways in acquired resistance against neurotoxin of 6-hydroxydopamine in SH-SY5Y cells following cell-cell interaction with astrocytes

Zhi-Gen Jiang, P. H. Yu

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Glial cells interact with neurons and play important roles in the development, differentiation, maintenance and repair of the nervous system. Human neuroblastoma cells (SH-SY5Y) became dramatically resistant to neurotoxin 6-hydroxydopamine (6-OHDA), when co-cultured with mouse astrocytes. In order to further delineate the molecular mechanism involved in the neuroprotection in this selective cell-cell interaction, we assessed the activation of two signal pathways, namely, the MAP kinases (extracellular signal-regulated kinases, ERK1/2) and phosphoinositide 3-kinase (PI3-K)/Akt signal pathways in response to 6-OHDA insult and subsequent neuronal survival. Western blot revealed that 6-OHDA significantly increased the phosphorylation of ERK1/2 and Akt in mono-cultured SH-SY5Y cells. However, the increase in ERK1/2 in SH-SY5Y cells after co-cultured with astrocytes occurred as early as 3 h after 6-OHDA treatment in oppose to the increase after 12 h in monocultures. The phosphorylation of Akt in the co-cultured SH-SY5Y cells was much pronounced 3 h after 6-OHDA treatment compared with that in the mono-cultured cells. The anti-apoptotic protein bcl-2 was also increased in the co-cultured SH-SY5Y cells 3 h after treatment with 6-OHDA. Selective inhibitor of PI3-K/Akt signal pathway blocked the acquired resistance to 6-OHDA in SH-SY5Y cells following interaction with astrocytes. Inhibition of ERK1/2 signal pathway did not affect the cell survival. Our data suggest that PI3-K/Akt signal pathway, but not ERK1/2, is involved the acquired resistance in SH-SY5Y cells following cell-cell interaction with astrocytes against the neurotoxic 6-OHDA insult.

Original languageEnglish (US)
Pages (from-to)405-411
Number of pages7
JournalNeuroscience
Volume133
Issue number2
DOIs
Publication statusPublished - 2005
Externally publishedYes

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Keywords

  • Neuroblastoma
  • Neuroprotection
  • Signal pathways

ASJC Scopus subject areas

  • Neuroscience(all)

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