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Dickkopf 3 attenuates xanthine dehydrogenase expression to prevent oxidative stress‐induced apoptosis
Author(s) -
Qui Shuang,
Kano Junko,
Noguchi Masayuki
Publication year - 2017
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12484
Subject(s) - gene knockdown , oxidative stress , biology , apoptosis , reactive oxygen species , microbiology and biotechnology , transfection , xanthine oxidase , biochemistry , enzyme , gene
Dickkopf ( DKK ) 3 is a DKK glycoprotein family member that controls cell fate during embryogenesis and exerts opposing effects on survival in a cell type‐dependent manner; however, the mechanisms governing its pro‐apoptosis versus pro‐survival functions remain unclear. Here, we investigated DKK 3 function in Li21 hepatoma cells and tPH 5 CH immortalized hepatocytes. DKK 3 knockdown by si RNA resulted in reactive oxygen species accumulation and subsequent apoptosis, which were abrogated by administration of the antioxidant N‐acetyl‐cysteine. Moreover, forced DKK 3 over‐expression induced resistance to hydrogen peroxide (H 2 O 2 )‐induced apoptosis. Expression analysis by cDNA microarray showed that xanthine dehydrogenase ( XDH ) expression was significantly lower in Li21 and tPH 5 CH DKK 3 ‐over‐expressing cells in response to H 2 O 2 treatment when compared to that in their respective mock‐transfected controls, whereas a marked increase was observed in H 2 O 2 ‐treated DKK 3 knockdown cells. Thus, these data suggest that DKK 3 promotes cell survival during oxidative stress by suppressing the expression of the superoxide‐producing enzyme XDH.