The involvement of Nrf2-ARE pathway in regulation of apoptosis in human glioblastoma cell U251

Neurol Res. 2013 Jan;35(1):71-8. doi: 10.1179/1743132812Y.0000000094. Epub 2012 Sep 20.

Abstract

Objectives: NF-E2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays anti-apoptotic role in normal tissue and tumor. But the role of Nrf2 in apoptosis in glioma is still unknown. Here, we established this experiment to elucidate how Nrf2-ARE pathway participates in apoptosis in human glioblastoma cell U251.

Methods: Two plasmids, pEGFP-Nrf2 and Si-Nrf2, were transfected to up- or downregulate the expression of Nrf2 in U251. After transfection, the apoptosis rate, expression of heme oxygenase-1 (HO-1), Bcl-2, Bax, caspases 3, 9 and activity of caspases 3, 9 were detected.

Results: After increasing expression of Nrf2, the apoptosis rate was reduced accompanied with upregulated expression of HO-1, Bcl-2/Bax, decreased expression and activity of caspases 3, 9. After decreasing expression of Nrf2, the apoptosis rate was enhanced accompanied with downregulated expression of HO-1, Bcl-2/Bax, increased expression and activity of caspases 3, 9.

Discussion: Our findings suggest that Nrf2 participates in the regulation of apoptosis in U251 through HO-1 and the 'intrinsic' apoptotic pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidant Response Elements / genetics
  • Antioxidant Response Elements / physiology*
  • Apoptosis / genetics
  • Apoptosis / physiology*
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Caspase 9 / genetics
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Expression Regulation, Neoplastic / physiology*
  • Glioblastoma / pathology
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism
  • Humans
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • Transfection
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • bcl-2-Associated X Protein
  • Green Fluorescent Proteins
  • Heme Oxygenase-1
  • Caspase 3
  • Caspase 9