RRC ID 71827
Author Qui S, Kano J, Noguchi M.
Title Dickkopf 3 attenuates xanthine dehydrogenase expression to prevent oxidative stress-induced apoptosis.
Journal Genes Cells
Abstract 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 DKK3 function in Li21 hepatoma cells and tPH5CH immortalized hepatocytes. DKK3 knockdown by siRNA resulted in reactive oxygen species accumulation and subsequent apoptosis, which were abrogated by administration of the antioxidant N-acetyl-cysteine. Moreover, forced DKK3 over-expression induced resistance to hydrogen peroxide (H2 O2 )-induced apoptosis. Expression analysis by cDNA microarray showed that xanthine dehydrogenase (XDH) expression was significantly lower in Li21 and tPH5CHDKK3-over-expressing cells in response to H2 O2 treatment when compared to that in their respective mock-transfected controls, whereas a marked increase was observed in H2 O2 -treated DKK3 knockdown cells. Thus, these data suggest that DKK3 promotes cell survival during oxidative stress by suppressing the expression of the superoxide-producing enzyme XDH.
Volume 22(4)
Pages 406-417
Published 2017-4-1
DOI 10.1111/gtc.12484
PMID 28299863
MeSH Adaptor Proteins, Signal Transducing Apoptosis* Cell Line Cell Line, Tumor Chemokines Gene Knockdown Techniques Humans Hydrogen Peroxide / metabolism Intercellular Signaling Peptides and Proteins / genetics Intercellular Signaling Peptides and Proteins / metabolism* Mitochondrial Membranes / metabolism Oxidative Stress* Xanthine Dehydrogenase / genetics*
IF 1.655
DNA material DKK3-FLAG (RDB19581)