Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 286, Issue 17, Pages 15085-15094Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M110.210971
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Funding
- National Genome Research Net Cardiovascular Diseases, Germany [BMBF/DLR-01GS0424/NHK-S12T21]
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Human vitamin K 2,3-epoxide reductase complex subunit 1-like 1 (VKORC1L1), expressed in HEK 293T cells and localized exclusively to membranes of the endoplasmic reticulum, was found to support both vitamin K 2,3-epoxide reductase (VKOR) and vitamin K reductase enzymatic activities. Michaelis-Menten kinetic parameters for dithiothreitol-driven VKOR activity were: K-m (mu M) = 4.15 (vitamin K-1 epoxide) and 11.24 (vitamin K-2 epoxide); V-max (nmol.mg(-1).hr(-1)) = 2.57 (vitamin K-1 epoxide) and 13.46 (vitamin K-2 epoxide). Oxidative stress induced by H2O2 applied to cultured cells up-regulated VKORC1L1 expression and VKOR activity. Cell viability under conditions of no induced oxidative stress was increased by the presence of vitamins K-1 and K-2 but not ubinquinone-10 and was specifically dependent on VKORC1L1 expression. Intracellular reactive oxygen species levels in cells treated with 2,3-dimethoxy-1,4-naphthoquinone were mitigated in a VKORC1L1 expression-dependent manner. Intracellular oxidative damage to membrane intrinsic proteins was inversely dependent on VKORC1L1 expression and the presence of vitamin K-1. Taken together, our results suggest that VKORC1L1 is responsible for driving vitamin K-mediated intracellular antioxidation pathways critical to cell survival.
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