An integrative genomic analysis identifies Bhmt2 as a diet-dependent genetic factor protecting against acetaminophen-induced liver toxicity.

Genome Research
Hong-Hsing LiuG Peltz

Abstract

Acetaminophen-induced liver toxicity is the most frequent precipitating cause of acute liver failure and liver transplant, but contemporary medical practice has mainly focused on patient management after a liver injury has been induced. An integrative genetic, transcriptional, and two-dimensional NMR-based metabolomic analysis performed using multiple inbred mouse strains, along with knowledge-based filtering of these data, identified betaine-homocysteine methyltransferase 2 (Bhmt2) as a diet-dependent genetic factor that affected susceptibility to acetaminophen-induced liver toxicity in mice. Through an effect on methionine and glutathione biosynthesis, Bhmt2 could utilize its substrate (S-methylmethionine [SMM]) to confer protection against acetaminophen-induced injury in vivo. Since SMM is only synthesized in plants, Bhmt2 exerts its beneficial effect in a diet-dependent manner. Identification of Bhmt2 and the affected biosynthetic pathway demonstrates how a novel method of integrative genomic analysis in mice can provide a unique and clinically applicable approach to a major public health problem.

References

Feb 1, 1992·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·G P BrayR Williams
Apr 15, 1987·Biochemical Pharmacology·J B BartoloneE A Khairallah
Jan 1, 1983·Annual Review of Biochemistry·A Meister, M E Anderson
Nov 24, 1999·Free Radical Biology & Medicine·O W Griffith
Apr 7, 2000·The American Journal of Pathology·C M HogaboamS L Kunkel
Mar 27, 2001·Biochemical and Biophysical Research Communications·T P ReillyL R Pohl
Dec 26, 2001·Toxicological Sciences : an Official Journal of the Society of Toxicology·Stefan U RueppFrançois Pognan
Aug 3, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yuko IshidaNaofumi Mukaida
Sep 11, 2002·Structure·John C EvansMartha L Ludwig
May 21, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Chuan ChenJose E Manautou
Sep 19, 2003·Toxicology and Applied Pharmacology·Pallavi B LimayeHarihara M Mehendale
Oct 15, 2003·Journal of Leukocyte Biology·Yuko IshidaNaofumi Mukaida
Nov 20, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Laura P JamesJack A Hinson
Mar 5, 2004·Cellular and Molecular Life Sciences : CMLS·H Jakubowski
Oct 1, 2004·Toxicological Sciences : an Official Journal of the Society of Toxicology·Grace L GuoFrank J Gonzalez
Oct 27, 2004·Toxicology Letters·Monica ValentovicA Betts Carpenter
Nov 10, 2004·Molecular and Cellular Biochemistry·Jingxiang Bai, Arthur I Cederbaum
Jun 21, 2005·Chemical Research in Toxicology·Kevin D WelchLance R Pohl
Jul 1, 2005·The Journal of Nutrition·Nathan R AugspurgerDavid H Baker
Jul 13, 2005·Trends in Genetics : TIG·Jianmei WangGary Peltz
Aug 20, 2005·Proceedings of the National Academy of Sciences of the United States of America·Yuzhi JiaJanardan K Reddy
Mar 24, 2006·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·James D Perkins
Apr 14, 2006·Toxicological Sciences : an Official Journal of the Society of Toxicology·Guoli DaiYu-Jui Yvonne Wan
Jun 1, 1990·Plant Physiology·S H Mudd, A H Datko
Jul 28, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Pallavi B LimayeHarihara M Mehendale
Oct 27, 2006·The Journal of Pharmacology and Experimental Therapeutics·Marcus V TerneusMonica A Valentovic
Sep 12, 2007·Bioinformatics·Ming ZhengGary Peltz
Jan 31, 2008·The Journal of Biological Chemistry·Sandra S SzegediTimothy A Garrow
Mar 14, 2008·Toxicology and Applied Pharmacology·Vishakha S BhaveHarihara M Mehendale
Aug 21, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Mary Jane MassonLance R Pohl
Nov 19, 2008·Chemico-biological Interactions·Yasuhiro MasubuchiToshiharu Horie
Jan 27, 2009·Journal of Clinical Gastroenterology·Linda J ChunJonathan R Hiatt

❮ Previous
Next ❯

Citations

Sep 4, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Alison H HarrillPaul B Watkins
Nov 29, 2011·Trends in Genetics : TIG·Ming ZhengGary Peltz
Sep 28, 2010·Toxicology and Applied Pharmacology·Stephanie M MartinezIvan Rusyn
Jul 29, 2010·European Journal of Oral Sciences·Adrianna MostowskaPawel P Jagodzinski
Sep 10, 2014·Drug Development Research·Endrit ToskaFeng Cheng
Sep 21, 2013·Molecular Metabolism·Andrew C AdamsAlexei Kharitonenkov
Aug 15, 2012·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Bahar Bilgin SokmenRefiye Yanardag
Oct 2, 2013·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Yihong LuLaura K Schnackenberg
Sep 16, 2016·Frontiers in Aging Neuroscience·Raquel Martínez-VegaMaría A Pajares
Jul 11, 2012·Journal of Medicinal Chemistry·Jana MládkováJiří Jiráček
Dec 1, 2017·Antioxidants & Redox Signaling·María A Pajares, Dolores Pérez-Sala
Oct 10, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Michael H CourtUNKNOWN Acute Liver Failure Study Group
Jun 1, 2012·The Journal of Pharmacology and Experimental Therapeutics·Jacinthe AubertBernard Fromenty
Feb 13, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Teresa PartearroyoIsabel Varela-Nieto
Oct 6, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·John S TregoningPeter J M Openshaw
Oct 24, 2013·Cutaneous and Ocular Toxicology·Havva Yıldız SeçkinMehmet Sahin
Oct 1, 2021·Frontiers in Genetics·Meiyue WangGary Peltz

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.