TY - JOUR
T1 - Depletion of 4-hydroxynonenal in hGSTA4-transfected HLE B-3 cells results in profound changes in gene expression
AU - Patrick, Brad
AU - Li, Jie
AU - Jeyabal, Prince V.S.
AU - Reddy, Prasada M.R.V.
AU - Yang, Yusong
AU - Sharma, Rajendra
AU - Sinha, Mala
AU - Luxon, Bruce
AU - Zimniak, Piotr
AU - Awasthi, Sanjay
AU - Awasthi, Yogesh C.
N1 - Funding Information:
Support for this study was provided in part by NIH Grants EY 04396, ES021171 (Y.C.A.), CA77495 (S.A.), and ES 07804 (P.Z.). B.P. is supported by NIEHS toxicology training grant ES 007254. Help from the core facilities of NIEHS Center grant ES06676 is acknowledged. The contents of this article are solely the responsibility of authors and do not necessarily represent the official view of NIH, NIEHS.
PY - 2005/8/26
Y1 - 2005/8/26
N2 - 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.
AB - 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.
KW - 4-Hydroxynonenal
KW - Apoptosis
KW - Cell cycle
KW - Glutathione
KW - Glutathione S-transferase
KW - Lipid peroxidation
KW - Transformation
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U2 - 10.1016/j.bbrc.2005.06.099
DO - 10.1016/j.bbrc.2005.06.099
M3 - Article
C2 - 16005854
AN - SCOPUS:22144461027
SN - 0006-291X
VL - 334
SP - 425
EP - 432
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -