Depletion of 4-hydroxynonenal in hGSTA4-transfected HLE B-3 cells results in profound changes in gene expression.
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 gamma1, connexin 43, Fas, integrin alpha6, TGFalpha, and c-jun was down-regulated, while the expression of protein kinase C beta II (PKCbetaII), c-myc, cyclin-dependent kinase 2 (CDK2), and TGFbeta 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.
Patrick
Brad
B
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, TX 77555, USA.
Li
Jie
J
Jeyabal
Prince V S
PV
Reddy
Prasada M R V
PM
Yang
Yusong
Y
Sharma
Rajendra
R
Sinha
Mala
M
Luxon
Bruce
B
Zimniak
Piotr
P
Awasthi
Sanjay
S
Awasthi
Yogesh C
YC
D000447:Aldehydes / Q000378:metabolism*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D019573:Epithelium, Corneal / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection / Q000379:methods
D000447:Aldehydes; D011994:Recombinant Proteins; D005982:Glutathione Transferase; C041116:leukotriene-C4 synthase; C027576:4-hydroxy-2-nonenal