Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P36969 (
phospholipid hydroperoxide glutathione peroxidase
)
344
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Docosahexaenoic acid (DHA; 22:6, n-3) is known to exert cytotoxic effects against various types of tumors via lipid peroxidation. Whereas several enzymes influence the response of cells to oxidative stress, only one enzyme,
phospholipid hydroperoxide glutathione peroxidase
(
GPx-4
), directly reduces lipid hydroperoxides in mammalian cells. The present study was designed to examine the involvement of
GPx-4
in determining the effects of DHA addition to various human cancer cell lines. Although baseline levels of
GPx-4
did not correlate with the relative sensitivity of human cancer cell lines to DHA, DHA reduced the level of protein expression of
GPx-4
by at least 50% in all six lines. Knockdown of
GPx-4
by small interfering RNA technique in a human
ovarian cancer
cell line significantly enhanced the cytotoxic effect of DHA in a time- and concentration-dependent manner. This cytotoxic effect of DHA was reversed by pretreatment with vitamin E, suggesting that the enhanced toxicity of
GPx-4
knockdown is due to changes in the ability of the cells to handle oxidative stress. Neither baseline superoxide dismutase-1 nor catalase expression correlated with the relative sensitivity of the cells to DHA treatment. These results illustrate that susceptibility to the oxidative stress imposed by DHA, and possibly other therapeutic agents, is due to complex interactions among multiple antioxidant systems. The modulation of
GPx-4
levels by DHA administration is of potential importance and may influence the cellular response to other oxidant stresses.
...
PMID:Phospholipid hydroperoxide glutathione peroxidase plays a role in protecting cancer cells from docosahexaenoic acid-induced cytotoxicity. 1743 Nov 26
