Transglutaminase inhibition protects against oxidative stress-induced neuronal death downstream of pathological ERK activation.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Manuela BassoRajiv R Ratan

Abstract

Molecular deletion of transglutaminase 2 (TG2) has been shown to improve function and survival in a host of neurological conditions including stroke, Huntington's disease, and Parkinson's disease. However, unifying schemes by which these cross-linking or polyaminating enzymes participate broadly in neuronal death have yet to be presented. Unexpectedly, we found that in addition to TG2, TG1 gene expression level is significantly induced following stroke in vivo or due to oxidative stress in vitro. Forced expression of TG1 or TG2 proteins is sufficient to induce neuronal death in Rattus norvegicus cortical neurons in vitro. Accordingly, molecular deletion of TG2 alone is insufficient to protect Mus musculus neurons from oxidative death. By contrast, structurally diverse inhibitors used at concentrations that inhibit TG1 and TG2 simultaneously are neuroprotective. These small molecules inhibit increases in neuronal transamidating activity induced by oxidative stress; they also protect neurons downstream of pathological ERK activation when added well after the onset of the death stimulus. Together, these studies suggest that multiple TG isoforms, not only TG2, participate in oxidative stress-induced cell death signaling; and that i...Continue Reading

References

Jun 1, 1997·Stroke; a Journal of Cerebral Circulation·A F SamdaniV L Dawson
Jun 25, 1998·The Journal of Cell Biology·S TanD Schubert
Jun 26, 1998·Free Radical Biology & Medicine·Y SagaraP Maher
Jun 23, 1999·Proceedings of the National Academy of Sciences of the United States of America·M V KarpujL Steinman
Mar 29, 2001·The Journal of Biological Chemistry·N NandaR M Graham
Dec 12, 2001·Neurochemistry International·Marcela V KarpujLawrence Steinman
Feb 14, 2002·Journal of Neurochemistry·Paul J TolentinoRonald L Hayes
Oct 9, 2002·The Biochemical Journal·Martin GriffinCarlo M Bergamini
Nov 30, 2002·The Journal of Biological Chemistry·Mathieu LesortGail V W Johnson
May 19, 2004·Journal of Neurochemistry·Paul J TolentinoRonald L Hayes
May 22, 2004·European Journal of Biochemistry·Charleen T ChuDonald B DeFranco
Jun 3, 2004·Neuroscience Letters·Riccardo IentileGioacchino Calapai
Nov 19, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Robert J FerranteRajiv R Ratan
Mar 11, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sunghee ChoCostantino Iadecola
Oct 18, 2005·The Journal of Biological Chemistry·Ambreena SiddiqRajiv R Ratan
Apr 11, 2006·The Journal of Clinical Investigation·Maria Borrell-PagèsSandrine Humbert
Dec 21, 2006·The Journal of Biological Chemistry·Sunghee ChoJohn T Pinto
May 2, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Eunhee KimSunghee Cho
May 7, 2008·The Journal of Experimental Medicine·Philipp S LangeRajiv R Ratan
Nov 17, 2009·Progress in Neuro-psychopharmacology & Biological Psychiatry·C GibratF Cicchetti
Dec 4, 2009·Autophagy·Manuela D'ElettoMauro Piacentini
Apr 17, 2010·Journal of Biomolecular Screening·Sabine SchaertlDouglas Macdonald
Jul 29, 2010·EMBO Molecular Medicine·Stephen J McConougheyRajiv R Ratan
Sep 22, 2010·Proceedings of the National Academy of Sciences of the United States of America·Renée E Haskew-LaytonRajiv R Ratan
Mar 4, 2011·Proceedings of the National Academy of Sciences of the United States of America·Marc A AntonyakRichard A Cerione
May 6, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sama F SleimanRajiv R Ratan
Sep 10, 2011·The FEBS Journal·Alexey M Belkin
Nov 11, 2011·International Journal of Molecular Sciences·Shang-Der ChenYao-Chung Chuang

❮ Previous
Next ❯

Citations

Jan 1, 1996·Life Sciences·J L Bankers-FulbrightD J McKean
Dec 20, 1988·Biochimica Et Biophysica Acta·M SalasE Parés
Feb 6, 2013·Proceedings of the National Academy of Sciences of the United States of America·Zhong-Qing ShiStuart A Lipton
Sep 7, 2013·Toxicological Sciences : an Official Journal of the Society of Toxicology·Márcio RibeiroA Cristina Rego
Nov 30, 2012·World Journal of Biological Chemistry·Martina IannacconeVittorio Gentile
Sep 10, 2014·Proceedings of the National Academy of Sciences of the United States of America·Kozo HamadaKatsuhiko Mikoshiba
Apr 11, 2013·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Manuela Basso, Rajiv R Ratan
Nov 29, 2014·CNS Neuroscience & Therapeutics·Pei-Cheng LiGao-Jun Teng
Oct 7, 2015·Molecular Brain·Monica SathyanesanSamuel S Newton
Apr 11, 2018·Antioxidants & Redox Signaling·David YoungJoris Messens
May 10, 2015·The Journal of Biological Chemistry·Ian YuAntonina Roll-Mecak
Sep 22, 2017·Human Molecular Genetics·Debasmita TripathyManuela Basso
May 31, 2018·Journal of Huntington's Disease·Nicholas R FranichJoan S Steffan
Mar 15, 2020·Experimental Lung Research·Elke BoxhammerMarietta von Suesskind-Schwendi
Apr 4, 2020·Cell Chemical Biology·Rajiv R Ratan
May 29, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Yangmin QiuNa Lu
Oct 27, 2020·Oxidative Medicine and Cellular Longevity·Sandro PercárioMaria Fani Dolabela
Apr 15, 2021·Cell Reports·Alice MigazziManuela Basso

❮ 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.