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PLoS One. 2017 Jul 11;12(7):e0181076. doi: 10.1371/journal.pone.0181076. eCollection 2017.

Inactivation of human DGAT2 by oxidative stress on cysteine residues.

Jung S1,2, Choi M1,2, Choi K1, Kwon EB2,3, Kang M1,2, Kim DE1,2, Jeong H1,2, Kim J4, Kim JH5, Kim MO3, Han SB2, Cho S1,6.

Author information

1
Anticancer Agent Research Center, Korea Research Institute of Bioscience & Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si, Chungcheongbuk-do, South Korea.
2
College of Pharmacy, Chungbuk National University, 1 Chungdae-ro Seowon-gu, Cheongju-si, Chungcheongbuk-do, South Korea.
3
Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si, Chungcheongbuk-do, South Korea.
4
Stem Cell Research Center, Korea Research Institute of Bioscience & Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon, South Korea.
5
Cancer Cell and Molecular Biology Branch, Research Institute, National Cancer Center, Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, South Korea.
6
Department of Biomolecular Science, Korea University of Science and Technology, 217 Gajeong-ro, Daejeon, South Korea.

Abstract

Diacylglycerol acyltransferases (DGATs) have a crucial role in the biosynthesis of triacylglycerol (TG), the major storage form of metabolic energy in eukaryotic organisms. Even though DGAT2, one of two distinct DGATs, has a vital role in TG biosynthesis, little is known about the regulation of DGAT2 activity. In this study, we examined the role of cysteine and its oxidation in the enzymatic activity of human DGAT2 in vitro. Human DGAT2 activity was considerably inhibited not only by thiol-modifying reagents (NEM and IA) but also by ROS-related chemicals (H2O2 and β-lapachone), while human DGAT1 and GPAT1 were little affected. Particularly, ROS-related chemicals concomitantly induced intermolecular disulfide crosslinking of human DGAT2. Both the oxidative inactivation and disulfide crosslinking were almost completely reversed by the treatment with DTT, a disulfide-reducing agent. These results clearly demonstrated the significant role of ROS-induced intermolecular crosslinking in the inactivation of human DGAT2 and also suggested DGAT2 as a redox-sensitive regulator in TG biosynthesis.

PMID:
28700690
PMCID:
PMC5507451
DOI:
10.1371/journal.pone.0181076
[Indexed for MEDLINE]
Free PMC Article

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