DNA Demethylation Upregulated Nrf2 Expression in Alzheimer's Disease Cellular Model

Frontiers in Aging Neuroscience
Huimin CaoGang Yu

Abstract

Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important transcription factor in the defense against oxidative stress. Cumulative evidence has shown that oxidative stress plays a key role in the pathogenesis of Alzheimer's disease (AD). Previous animal and clinical studies had observed decreased expression of Nrf2 in AD. However, the underlying regulation mechanisms of Nrf2 in AD remain unclear. Here, we used the DNA methyltransferases (Dnmts) inhibitor 5-aza-2'-deoxycytidine (5-Aza) to test whether Nrf2 expression was regulated by methylation in N2a cells characterizing by expressing human Swedish mutant amyloid precursor protein (N2a/APPswe). We found 5-Aza treatment increased Nrf2 at both messenger RNA and protein levels via downregulating the expression of Dnmts and DNA demethylation. In addition, 5-Aza-mediated upregulation of Nrf2 expression was concomitant with increased nuclear translocation of Nrf2 and higher expression of Nrf2 downstream target gene quinone oxidoreductas (NQO1). Our study showed that DNA demethylation promoted the Nrf2 cell signaling pathway, which may enhance the antioxidant system against AD development.

References

Dec 6, 1994·Proceedings of the National Academy of Sciences of the United States of America·R JüttermannR Jaenisch
Aug 12, 1999·Inflammation·E SchwartzJ Golenser
Jan 1, 2003·Cancer Detection and Prevention·Yi Y QiuRama S Dwivedi
Dec 21, 2004·International Journal of Cancer. Journal International Du Cancer·Karin SchmelzIngo Tamm
Oct 8, 2005·Seminars in Oncology·Richard L Momparler
Jan 6, 2007·Journal of Neuropathology and Experimental Neurology·Chenere P RamseyKelly L Jordan-Sciutto
Jul 12, 2008·Molecular Carcinogenesis·Wenge Li, Ah-Ng Kong
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Katja KanninenJari Koistinaho
May 25, 2011·Current Alzheimer Research·Jessica L FlemingAmanda Ewart Toland
Jul 26, 2011·Archives of Gerontology and Geriatrics·Koji TomobeYasuyuki Nomura
Sep 20, 2011·Cell·Nidhi BhutaniHelen M Blau
Dec 12, 2012·Biochemical Pharmacology·Holly K BryanB Kevin Park
Feb 19, 2013·Biochemical Pharmacology·Chengyue ZhangAh-Ng Tony Kong
Apr 9, 2013·Pharmacology & Therapeutics·Lina Adwan, Nasser H Zawia
Aug 29, 2013·Oxidative Medicine and Cellular Longevity·Yan Zhao, Baolu Zhao
Dec 25, 2013·Frontiers in Aging Neuroscience·Haoyang LuHong Qing
Feb 14, 2014·BioMed Research International·Carlo CervellatiGiovanni Zuliani
Mar 29, 2014·Nature Communications·Chulman JoGail V W Johnson
May 14, 2014·Frontiers in Oncology·Dharmalingam SubramaniamShrikant Anant
Feb 26, 2015·Pharmacological Reports : PR·Anil Kumar Ekavali
Mar 31, 2015·Nature Genetics·Jing LiaoAlexander Meissner
May 15, 2015·Oxidative Medicine and Cellular Longevity·Sara PorcellottiSandra Moreno

❮ Previous
Next ❯

Citations

Sep 22, 2017·Diseases·Bodo C Melnik, Gerd Schmitz
Jul 22, 2018·Molecular and Cellular Biochemistry·Gökhan KasnakUlvi K Gürsoy
Jul 3, 2021·International Journal of Molecular Sciences·Chand Basha DavuljigariGaku Ichihara
Mar 13, 2019·European Journal of Pharmacology·Chao HuangZhuo Chen

❮ Previous
Next ❯

Methods Mentioned

BETA
nuclear translocation
PCR
nuclear

Related Concepts

Related Feeds

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.