Inactivation of human DGAT2 by oxidative stress on cysteine residues

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 DGAT...

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Bibliographic Details
Published in:PloS one 2017-07, Vol.12 (7), p.e0181076-e0181076
Main Authors: Jung, Sunhee, Choi, Miri, Choi, Kwangman, Kwon, Eun Bin, Kang, Mingu, Kim, Dong-Eun, Jeong, Hyejeong, Kim, Janghwan, Kim, Jong Heon, Kim, Mun Ock, Han, Sang-Bae, Cho, Sungchan
Format: Article
Language:English
Subjects:
Biology and Life Sciences
Biosynthesis
Biotechnology
Cancer
Chemicals
Crosslinking
Cysteine
Cysteine - metabolism
Deactivation
Diacylglycerol
Diacylglycerol O-Acyltransferase - metabolism
Diglycerides
Dithiothreitol
Endoplasmic reticulum
Energy metabolism
Energy storage
Enzymatic activity
Enzymes
Fatty acids
Glycerol
Humans
Hydrogen peroxide
Hydrogen Peroxide - pharmacology
In vitro methods and tests
Inactivation
Inhibition
Lapachone
Lipids
Metabolic disorders
Oxidation
Oxidative stress
Oxidative Stress - drug effects
Oxidative Stress - physiology
Pharmaceutical sciences
Pharmacy
Physical Sciences
Proteins
Reactive oxygen species
Reactive Oxygen Species - metabolism
Reagents
Research and Analysis Methods
Residues
Studies
Triglycerides - metabolism
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0181076