20 - World Journal of Gastroenterology

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doi:10.3748/wjg.v17.i20.2552
Natalia A Osna, MD, PhD, Series Editor
Role of MGST1 in reactive intermediate-induced injury
Courtney S Schaffert
Courtney S Schaffert, Department of Biochemistry and Molecular
Biology, University of Nebraska Medical Center, Omaha,
NE 68198-5870, United States
Author contributions: Schaffert CS solely contributed to this
review.
Correspondence to: Courtney S Schaffert, PhD, Department
of Biochemistry and Molecular Biology, University of
Nebraska Medical Center, Omaha, NE 68198-5870,
United States. cschaffert@unmc.edu
Telephone: +1-402-5596647 Fax: +1-402-5596650
Received: March 17, 2011 Revised: April 15, 2011
Accepted: April 22, 2011
Published online: May 28, 2011
Abstract
Microsomal glutathione transferase (MGST1, EC 2.5.1.18)
is a membrane bound glutathione transferase extensively
studied for its ability to detoxify reactive intermediates,
including metabolic electrophile intermediates and lipophilic
hydroperoxides through its glutathione dependent
transferase and peroxidase activities. It is expressed in
high amounts in the liver, located both in the endoplasmic
reticulum and the inner and outer mitochondrial
membranes. This enzyme is activated by oxidative stress.
Binding of GSH and modification of cysteine 49 (the oxidative
stress sensor) has been shown to increase activation
and induce conformational changes in the enzyme.
These changes have either been shown to enhance the
protective effect ascribed to this enzyme or have been
shown to contribute to cell death through mitochondrial
permeability transition pore formation. The purpose of
this review is to elucidate how one enzyme found in two
places in the cell subjected to the same conditions of oxidative
stress could both help protect against and contribute
to reactive oxygen species-induced liver injury.
© 2011 Baishideng. All rights reserved.
Key words: Microsomal glutathione transferase 1; Oxidative
stress; Mitochondrial permeability transition; Glutathione;
Liver injury
WJG|www.wjgnet.com
2552
World J Gastroenterol 2011 May 28; 17(20): 2552-2557
ISSN 1007-9327 (print) ISSN 2219-2840 (online)
© 2011 Baishideng. All rights reserved.
Peer reviewers: Vasiliy I Reshetnyak, MD, PhD, Professor,
Scientist Secretary of the Scientific Research Institute of General
Reanimatology, 25-2, Petrovka str., 107031, Moscow, Russia;
Jay Pravda, MD, Inflammatory Disease Research Center,
Gainesville, FL 32614-2181, United States
Schaffert CS. Role of MGST1 in reactive intermediate-induced
injury. World J Gastroenterol 2011; 17(20): 2552-2557 Available
from: URL: http://www.wjgnet.com/1007-9327/full/v17/
i20/2552.htm DOI: http://dx.doi.org/10.3748/wjg.v17.i20.2552
INTRODUCTION
TOPIC HIGHLIGHT
Tissue damage due to excessive production of reactive intermediates
(reactive oxygen species (ROS), reactive nitrogen
species (RNS), lipid peroxides, free radicals) has been
shown to be a major part of various pathologies including
atherosclerosis, diabetes, cancer, ischemia-reperfusion
injury, aging, and liver injury from both alcoholic and
non-alcoholic origins [1-3] . Organisms have evolved many
defense mechanisms as protection from these reactive
intermediates. These include, but aren’t limited to, various
enzymes such as superoxide dismutase, Se-dependent glutathione
peroxidase, catalase, glutaredoxins, peroxiredoxins,
and glutathione transferases (GSTs) [4] . GSTs bind and
conjugate electrophiles to GSH to, in effect, neutralize
them, and protect the cells. Some GSTs also have glutathione
peroxidase activities. While many GSTs are cytosolic,
other GSTs exist that are integral membrane proteins.
They are members of the membrane associated proteins
in eicosanoid and glutathione metabolism (MAPEG) family,
which include enzymes that synthesize prostaglandins
and leukotrienes. Microsomal glutathione transferase 1
(MGST1) is a member of this family and is the subject of
the following review.
MGST1 STRUCTURE AND FUNCTION
MGST1 is an approximately 17 kDa membrane bound
glutathione s-transferase [5] . It is found in the highest
May 28, 2011|Volume 17|Issue 20|