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Ciccia, Marie-Noëlle

doi:10.4000/books.pulm.926

Cited by 2 publications

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“…The study of the mechanisms of DNA damage and repair is critically important to understanding the origins of cancer. 1,2 DNA glycosylases are a class of DNA repair enzyme responsible for initiating base excision repair (BER). [3][4][5][6] Enzymes of this broad class recognize damaged or mispaired DNA bases and hydrolyze the N-glyosidic bond between the targeted base and the sugar (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

“…Most glycosylases play a genoprotective role, preventing the accumulation of cytotoxic mutations in the genome. 2 For example, two important human glycosylases are OGG1, 7,8 which excises 8-oxoguanine, one of the most common oxidized lesions in DNA, 2 and UNG, 9 which removes uracil arising from cytosine deamination. Because these forms of damage lead to mutations, DNA glycosylases such as OGG1 have been extensively investigated for their role in oncogenesis.…”

Section: Introductionmentioning

confidence: 99%

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Ultrafast Oxime Formation Enables Efficient Fluorescence Light-up Measurement of DNA Base Excision

Wilson

Kool

2019

J. Am. Chem. Soc.

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DNA glycosylases constitute a biologically and biomedically important group of DNA repair enzymes responsible for initiating base excision repair (BER). Measuring their activities can be useful for studying the mechanisms DNA damage and repair and for practical applications in cancer diagnosis and drug screening. Previous fluorescence methods for assaying DNA glycosylases are often complex and/or limited in scope to a single enzyme type. Here we report a universal base excision reporter (UBER) fluorescence probe design that implements an unprecedentedly rapid oxime reaction (>150 M −1 s −1 ) with high specificity for the abasic (AP) site of DNA. The molecular rotor design achieves a robust >250-500-fold increase in fluorescence upon reaction with AP sites in DNA. By using the fluorescence reporter in concert with specific DNA lesion-containing substrates, the UBER probe can be used in a coupled assay in principle with any DNA glycosylase. We demonstrate the utility of the UBER probe by assaying five different glycosylases in real time as well as profiling glycosylase activity in cell lysates. We anticipate that the UBER probe will be of considerable utility to researchers studying DNA repair biology owing to its high level of generalizability, ease of use, and compatibility with biologically derived samples.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ultrafast Oxime Formation Enables Efficient Fluorescence Light-up Measurement of DNA Base Excision

Wilson

Kool

2019

J. Am. Chem. Soc.

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“…Generally, Th17 response in autoimmune disorders has been believed to cause neurons death or inflammatory response 34,35 . Besides, previous studies also have shown that type 3 innate lymphoid cell (ILC3) produce IL-17 in autoimmune disorder such as ankylosing spondylitis 36 and that ILC3 can maintains neuroinflammation by supporting T cell survival 37 . Thus, both neuroinflammation and demyelination were largely believed to be mediated by Th17-and ILC3-related responses.…”

Section: Discussionmentioning

confidence: 99%

Brain tissue-derived autoimmune encephalitis cytokine TSLP primes neuroinflammation by activating JAK2-NLRP3 axis

et al. 2021

Preprint

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Hyperactivation of NLRP3 inflammasome contributes to the neuroinflammation in autoimmune disorders, but the underlying regulating mechanism remains to be elucidated. We here demonstrate that mice lacking thymic stromal lymphopoietin receptor gene (Tslpr-/-) exhibit significant decreases in experimental autoimmune encephalitis (EAE) score, reduced CD4+ T cells infiltration, and restored expression of myelin basic protein (MBP) in the brain after induction of EAE by injection of myelin oligodendrocyte glycoprotein35-55 (MOG35-55) . TSLPR signals through Janus Kinase 2 (JAK2) to activate NLRP3. Tslpr-/- mice of EAE show decreased phosphorylation of JAK2 and expression of NLRP3 in the brain. In wild type (WT) mice after induction of EAE, inhibition of JAK2 by ruxolitinib inflammatory and CD4+ cell infiltration, decreased expression of NLRP3, and restored BMP expression in the brain. Ruxolitinib also decreased levels of IL-1β and TSLP in brain of EAE mouse when compared to that without ruxolitinib treatment. Further results with NLRP3 inhibitor MCC950 in EAE mouse of WT verified the proinflammatory role of NLRP3 by showing decreased inflammatory cells and CD4+ T cells, restored MBP expression, and declined levels of IL-1β and TSLP in the brain. In patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis we found increased level of NLRP3 and IL-1β in CSF when compared to that in control subjects. These findings highlight TSLP as a prospective target for treating JAK2-NLRP3 axis-associated autoimmune inflammatory disorders.

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Présentation

Cited by 2 publications

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Ultrafast Oxime Formation Enables Efficient Fluorescence Light-up Measurement of DNA Base Excision

Ultrafast Oxime Formation Enables Efficient Fluorescence Light-up Measurement of DNA Base Excision

Brain tissue-derived autoimmune encephalitis cytokine TSLP primes neuroinflammation by activating JAK2-NLRP3 axis

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