HDAC1 modulates OGG1-initiated oxidative DNA damage repair in the aging brain and Alzheimer’s disease

Pao, Ping‐Chieh; Patnaik, Debasis; Watson, L. Ashley; Gao, Fan; Pan, Ling; Wang, Jun; Adaikkan, Chinnakkaruppan; Penney, Jay; Cam, Hugh P.; Huang, Wen‐Chin; Pantano, Lorena; Lee, Audrey; Nott, Alexi; Phan, Trongha; Gjoneska, Elizabeta; Elmsaouri, Sara; Haggarty, Stephen J.; Tsai, Li‐Huei

doi:10.1038/s41467-020-16361-y

Cited by 143 publications

(121 citation statements)

References 70 publications

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“…SIRT6 is an important regulator of DNA repair enzymes and a chromatin modifier in response to DNA damage; its reduction plays a critical role in genomic instability [ 58 ]. Class I HDACs also decrease their activity during aging, which is especially pronounced in the brain [ 59 , 60 , 61 ]. These proteins are assembled into the nucleosome remodeling and deacetylation complex (NuRD), which is involved in the regulation of nucleosome position, and histone deacetylase activity and controls DNA damage response [ 60 ].…”

Section: Impairment Of the Mechanisms For Maintaining Genome Stabimentioning

confidence: 99%

“…These proteins are assembled into the nucleosome remodeling and deacetylation complex (NuRD), which is involved in the regulation of nucleosome position, and histone deacetylase activity and controls DNA damage response [ 60 ]. A member of this class, HDAC1, provides chromatin structure maintenance as well as is essential for DNA repair and replication processes [ 61 , 62 ]. At the same time, enhanced activation of classes I and II HDACs causes cancer and some other chronic diseases [ 62 , 63 ].…”

Section: Impairment Of the Mechanisms For Maintaining Genome Stabimentioning

confidence: 99%

“…Recently, it has been found that HDAC1 stimulates the OGG1 DNA glycosylase, which is involved in BER and removes 8-oxoG. Pharmacological activation of HDAC1 with exifone attenuates 8-oxoG repair in old wild-type mice and in a model of Alzheimer’s disease, while HDAC1 deficiency has the opposite effect [ 61 ].…”

Section: Pharmacological Interventions Protecting Genomementioning

confidence: 99%

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Genome-Protecting Compounds as Potential Geroprotectors

Proshkina

Shaposhnikov

Moskalev

2020

IJMS

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Throughout life, organisms are exposed to various exogenous and endogenous factors that cause DNA damages and somatic mutations provoking genomic instability. At a young age, compensatory mechanisms of genome protection are activated to prevent phenotypic and functional changes. However, the increasing stress and age-related deterioration in the functioning of these mechanisms result in damage accumulation, overcoming the functional threshold. This leads to aging and the development of age-related diseases. There are several ways to counteract these changes: (1) prevention of DNA damage through stimulation of antioxidant and detoxification systems, as well as transition metal chelation; (2) regulation of DNA methylation, chromatin structure, non-coding RNA activity and prevention of nuclear architecture alterations; (3) improving DNA damage response and repair; (4) selective removal of damaged non-functional and senescent cells. In the article, we have reviewed data about the effects of various trace elements, vitamins, polyphenols, terpenes, and other phytochemicals, as well as a number of synthetic pharmacological substances in these ways. Most of the compounds demonstrate the geroprotective potential and increase the lifespan in model organisms. However, their genome-protecting effects are non-selective and often are conditioned by hormesis. Consequently, the development of selective drugs targeting genome protection is an advanced direction.

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Section: Impairment Of the Mechanisms For Maintaining Genome Stabimentioning

confidence: 99%

Section: Impairment Of the Mechanisms For Maintaining Genome Stabimentioning

confidence: 99%

Section: Pharmacological Interventions Protecting Genomementioning

confidence: 99%

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Genome-Protecting Compounds as Potential Geroprotectors

Proshkina

Shaposhnikov

Moskalev

2020

IJMS

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“…Accumulation of DNA damage, the main reason for excessive apoptosis/death of neural cells, is a critical pathological cause of neurological diseases [16][17][18][19]. During neurodevelopment, the rapid cellular proliferation can lead to replication-induced DNA damage [20].…”

Section: Ivyspringmentioning

confidence: 99%

“…During neurodevelopment, the rapid cellular proliferation can lead to replication-induced DNA damage [20]. In mature brains, neural cells are also prone to DNA damage caused by metabolites including oxygen free radicals, homocysteine and amyloid β-peptide (Aβ) [4,17,19,21]. Failure to effectively overcome DNA damage results in damage accumulation, mitotic catastrophe, chromosomal rearrangements, and cell death.…”

Section: Ivyspringmentioning

confidence: 99%

Homocysteine aggravates DNA damage by impairing the FA/Brca1 Pathway in NE4C murine neural stem cells

et al. 2020

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There is existing evidence that elevated homocysteine (Hcy) levels are risk factors for some neurodegenerative disorders. The pathogenesis of neurological diseases could be contributed to excessive cell dysfunction and death caused by defective DNA damage response (DDR) and accumulated DNA damage. Hcy is a neurotoxic amino acid and acts as a DNA damage inducer. However, it is not clear whether Hcy participates in the DDR. To investigate the effects of Hcy on DNA damage and the DDR, we employed mitomycin C (MMC) to cause DNA damage in NE4C murine neural stem cells (NSCs). Compared to treatment with MMC alone, we found that co-treatment with MMC and Hcy worsened DNA damage and increased death in NE4C cells. Intriguingly, in this DNA damage model mimicked by MMC, immunoblotting results showed that the monoubiquitination levels of Fanconi anemia complementation group I (Fanci) and Fanconi anemia complementation group D2 (Fancd2) were decreased to about 60.3% and 55.7% by supplementing cell culture medium with Hcy, indicating Hcy inactivates the function of Fanci and Fancd2 in DNA damage conditions. Given Breast Cancer 1 (BRCA1) is an important downstream of FANCD2, we next detected the interaction between Fancd2 and Brca1 in NE4C cells. Compared to treatment with MMC alone, the Fancd2-Brca1 interaction and the amount of Brca1 on chromatin were decreased when cells were co-exposed to MMC and Hcy, suggesting Hcy could impair the Fanconi anemia (FA)/Brca1 pathway. Taken together, our study demonstrates that Hcy may enhance cell death, which contributes to the accumulation of DNA damage and promotion of hypersensitivity to cytotoxicity by impairing the FA/Brca1 pathway in murine NSCs in the presence of DNA damage.

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Pharmacognostic standardization and machine learning–based investigations on Akebia quinata and Akebia trifoliata

Qiu

Shi

2023

Biomedical Chromatography

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Currently, Akebiae Caulis is being used in clinical practice, but there are few reseaches on its different varieties. To ensure the accuracy and effectiveness of clinical practice, this study distinguished the Akebia quinata (Thunb.) Decne. and Akebia trifoliata (Thunb.) Koidz, using organoleptic evaluation, microscopic observation, fluorescence reaction, physicochemical properties, thin‐layer chromatography, IR spectroscopy, HPLC, four machine learning models, and in vitro antioxidant methods. Analysis of the powders of these two varieties using optical microscopy revealed the presence of starch granules, cork cells, crystal fibers, scalariform vessels, and wood fibers. Scanning electron microscopy revealed the presence of scalariform vessels, pitted vessels, wood fibers, and calcium oxalate crystals. Several tissues, including the cork layer, fiber population, cortex, phloem, pith, xylem, and ray, were found in the transverse section. In addition, thin‐layer chromatography was used to identify two components: oleanolic acid and calceolarioside B; 11 common peaks were identified in 15 batches of SAQ and 5 batches of SAT by using HPLC. Support vector machine, BP neural networks, and GA‐bp neural networks were able to predict 100% accurately of the different origins of stem of Akebia quinate (Thunb.) Decne (SAQ) and Akebia trifoliata (Thunb.) Koidz (SAT). Extreme learning machine achieved a correct rate of 87.5%. Meanwhile, Fourier‐transform infrared spectroscopy fingerprint identified nine characteristic absorption peaks of the secondary metabolites of SAQ and SAT. 2,2‐Diphenyl‐1‐1‐picrylhydrazyl experiment revealed that the IC50 values of SAQ and SAT extracts were 155.49 and 128.75 μg/ml, respectively. For the 2,2′‐azino‐bis‐(3‐ethylbenzothiazoline‐6‐sulfonic acid) assay, the IC50 value of SAT extract was found to be 269.24 μg/ml, which was lower than that of SAQ extract (IC50 = 358.99 μg/ml). This study successfully used different methods to differentiate between A. quinata (Thunb.) Decne. and A. trifoliata (Thunb.) Koidz., to help decide on which type to use for clinical application.

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HDAC1 modulates OGG1-initiated oxidative DNA damage repair in the aging brain and Alzheimer’s disease

Cited by 143 publications

References 70 publications

Genome-Protecting Compounds as Potential Geroprotectors

Genome-Protecting Compounds as Potential Geroprotectors

Homocysteine aggravates DNA damage by impairing the FA/Brca1 Pathway in NE4C murine neural stem cells

Pharmacognostic standardization and machine learning–based investigations on Akebia quinata and Akebia trifoliata

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