Depletion of 4-hydroxynonenal in hGSTA4-transfected HLE B-3 cells results in profound changes in gene expression

Brad Patrick, Jie Li, Prince V.S. Jeyabal, Prasada M.R.V. Reddy, Yusong Yang, Rajendra Sharma, Mala Sinha, Bruce Luxon, Piotr Zimniak, Sanjay Awasthi, Yogesh C. Awasthi

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Previously, we have shown that overexpression of 4-hydroxy-2-nonenal (HNE)-detoxifying enzyme glutathione S-transferase A4-4 (hGSTA4-4) in human lens epithelial cells (HLE B-3) leads to pro-carcinogenic phenotypic transformation of these cells [R. Sharma, et al. Eur. J. Biochem. 271 (2004) 1960-1701]. We now demonstrate that hGSTA4-transfection also causes a profound change in the expression of genes involved in cell adhesion, cell cycle control, proliferation, cell growth, and apoptosis, which is consistent with phenotypic changes of the transformed cells. The expression of p53, p21, p16, fibronectin 1, laminin γ1, connexin 43, Fas, integrin α6, TGFα, and c-jun was down-regulated, while the expression of protein kinase C beta II (PKCβII), c-myc, cyclin-dependent kinase 2 (CDK2), and TGFβ was up-regulated in transfected cells. These results demonstrate that HNE serves as a crucial signaling molecule and, by modulating the expression of genes, can influence cellular functions.

Original languageEnglish (US)
Pages (from-to)425-432
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume334
Issue number2
DOIs
StatePublished - Aug 26 2005

Keywords

  • 4-Hydroxynonenal
  • Apoptosis
  • Cell cycle
  • Glutathione
  • Glutathione S-transferase
  • Lipid peroxidation
  • Transformation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Patrick, B., Li, J., Jeyabal, P. V. S., Reddy, P. M. R. V., Yang, Y., Sharma, R., Sinha, M., Luxon, B., Zimniak, P., Awasthi, S., & Awasthi, Y. C. (2005). Depletion of 4-hydroxynonenal in hGSTA4-transfected HLE B-3 cells results in profound changes in gene expression. Biochemical and Biophysical Research Communications, 334(2), 425-432. https://doi.org/10.1016/j.bbrc.2005.06.099