SIRT2 protects peripheral neurons from cisplatin-induced injury by enhancing nucleotide excision repair.

The Journal of Clinical Investigation
Manchao ZhangFen Xia

Abstract

Platinum-based chemotherapy-induced peripheral neuropathy is one of the most common causes of dose reduction and discontinuation of life-saving chemotherapy in cancer treatment; it often causes permanent impairment of quality of life in cancer patients. The mechanisms that underlie this neuropathy are not defined, and effective treatment and prevention measures are not available. Here, we demonstrate that SIRT2 protected mice against cisplatin-induced peripheral neuropathy (CIPN). SIRT2 accumulated in the nuclei of dorsal root ganglion sensory neurons and prevented neuronal cell death following cisplatin treatment. Mechanistically, SIRT2, an NAD+-dependent deacetylase, protected neurons from cisplatin cytotoxicity by promoting transcription-coupled nucleotide excision repair (TC-NER) of cisplatin-induced DNA cross-links. Consistent with this mechanism, pharmacological inhibition of NER using spironolactone abolished SIRT2-mediated TC-NER activity in differentiated neuronal cells and protection of neurons from cisplatin-induced cytotoxicity and CIPN in mice. Importantly, SIRT2's protective effects were not evident in lung cancer cells in vitro or in tumors in vivo. Taken together, our results identified SIRT2's function in the N...Continue Reading

References

Dec 1, 1990·Journal of Neuro-oncology·W BoogerdJ J van der Sande
Jun 28, 2001·Nature Structural Biology·M S FinninN P Pavletich
Nov 8, 2001·European Journal of Pharmacology·M Zimmermann
Mar 7, 2003·Molecular Cell·Brian J NorthEric Verdin
May 23, 2003·Cold Spring Harbor Symposia on Quantitative Biology·R D WoodM K Shivji
Apr 20, 2004·International Journal of Cancer. Journal International Du Cancer·Carey WelshBeate Köberle
Sep 14, 2004·Journal of Neurobiology·Gary R Lewin, Rabih Moshourab
Sep 2, 2006·Neurotoxicology·Anke Tomaszewski, Dietrich Büsselberg
Jun 15, 2007·Journal of the Peripheral Nervous System : JPNS·Weiran ChenAhmet Höke
Aug 31, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Anna DzagnidzeJuergen Thomale
Sep 18, 2010·European Journal of Pharmacology·Amteshwar Singh Jaggi, Nirmal Singh
Sep 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Bogdan BeirowskiJeffrey Milbrandt
Mar 10, 2012·Frontiers in Pharmacology·Franziska Flick, Bernhard Lüscher
Dec 19, 2012·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Mohammad Waseem, Suhel Parvez
Jan 3, 2013·Psychiatry and Clinical Neurosciences·Mustafa GulecHalis Suleyman
Jul 31, 2013·Proceedings of the National Academy of Sciences of the United States of America·Hui ZhangDavid S Yu
Aug 29, 2013·Cell Biology and Toxicology·Valeria Maria PiccoliniGraziella Bernocchi
Jun 1, 2012·Liver Cancer·Norihiro Kokudo, Takeaki Ishizawa
Nov 2, 2013·Journal of Molecular Biology·Johannes G M RackMathias Ziegler
Dec 18, 2013·Science·Ophir ShalemFeng Zhang
Jan 5, 2014·Frontiers in Pharmacology·Yaqin Han, Maree T Smith
May 13, 2014·DNA Repair·Renate Hvidsten SkogeMathias Ziegler
May 16, 2014·The EMBO Journal·Brian J NorthDavid A Sinclair
Jul 18, 2014·Neuron·Ram MadabhushiLi-Huei Tsai
Jul 31, 2014·Nature Methods·Neville E SanjanaFeng Zhang
Dec 3, 2014·Neuroscience Letters·V A CarozziA Chiorazzi
Feb 13, 2015·Nature Communications·Tobias RumpfManfred Jung
Jun 24, 2015·Proceedings of the National Academy of Sciences of the United States of America·Leizhen WeiLi Lan

❮ Previous
Next ❯

Citations

May 18, 2020·Biomolecules·Ryan D GabbardMichael G Kemp
Jul 4, 2020·Signal Transduction and Targeted Therapy·Zhe ZhangCanhua Huang
Nov 13, 2020·Drug Development Research·Vishal PatelMukul Jain
Apr 1, 2021·Cell Reports·Elizabeth V MintenDavid S Yu
Jun 3, 2021·International Journal of Molecular Sciences·Iwona KarwaciakMarcin Ratajewski

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
acetylation
xenograft
transfection
dot blot
genotyping
dissection
fluorescence microscopy
dot blotting
Assay

Software Mentioned

GraphPad
Prism

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.