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c‐myc ‐dependent hepatoma cell apoptosis results from oxidative stress and not a deficiency of growth factors
Author(s) -
Xu Yang,
Nguyen Quynh,
Lo Danica C.,
Czaja Mark J.
Publication year - 1997
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199702)170:2<192::aid-jcp11>3.0.co;2-k
Subject(s) - glutamine , apoptosis , intracellular , oxidative stress , programmed cell death , glutathione , catalase , cell growth , cell culture , biology , asparagine , chemistry , biochemistry , amino acid , enzyme , genetics
Expression of c‐myc regulates apoptotic cell death in the human hepatoma cell line HuH‐7 during culture in serum‐free medium (SFM) plus zinc. To understand the mechanism of this c‐myc effect, the ability of various serum‐contained factors to prevent apoptosis was determined. Apoptosis was not inhibited by growth factors and was even accelerated by supplementation with insulin‐like growth factor I or insulin. Cell death was prevented by SFM supplementation with the amino acid glutamine but not serine or asparagine. Improved cell survival with glutamine was associated with increased levels of glutathione (GSH). In HuH‐7 cells cultured in SFM plus zinc, c‐myc expression led to decreased levels of GSH, and elevated intracellular levels of hydrogen peroxide (H 2 O 2 ). Cell death induced by c‐myc expression was inhibited by the addition of catalase or dimethyl sulfoxide, a hydroxyl radical scavenger, or by increased intracellular expression of catalase. In contrast to findings in fibroblasts, c‐myc ‐dependent apoptosis during serum deprivation in HuH‐7 hepatoma cells was unrelated to a loss of growth factors. Apoptosis resulted from H 2 O 2 ‐mediated oxidative stress with associated glutamine dependent intracellular GSH depletion. J. Cell. Physiol. 170:192–199, 1997. © 1997 Wiley‐Liss, Inc.