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

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    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

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    Keywords

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

    ASJC Scopus subject areas

    • Biochemistry
    • Biophysics
    • Molecular Biology

    Cite this

    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