Elevated glucose increases genomic instability by inhibiting nucleotide excision repair

Ciminera, Alexandra K; Shuck, Sarah C.; Termini, John

doi:10.26508/lsa.202101159

Cited by 18 publications

(19 citation statements)

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“…HIF-1α modification by MG decreases heterodimer formation and promoter binding . This is a potential mechanism for the decreased DNA repair protein expression in cells grown in high glucose observed by Ciminera et al as DNA repair proteins are targets for HIF-1α transcription activity . Recently, work from Marnett demonstrated that histones are targets for MG modification, potentially regulating gene expression .…”

Section: Mg-protein Adducts: Formation and Impact On Structure And Fu...mentioning

confidence: 95%

“…Ciminera et al recently showed that high glucose decreased the expression of proteins in the NER pathway, leading to accumulation of MG-DNA adducts corresponding to decreased functional repair. 87 The authors suggested that high glucose may downregulate NER protein expression through a HIF-1α-dependent mechanism. 87 When cells are unable to efficiently repair DNA damage, it leads to persistent lesions that may cause genomic instability and mutations (Figure 4A).…”

Section: ■ Mg-ages On Dna and Proteinmentioning

confidence: 99%

“…87 The authors suggested that high glucose may downregulate NER protein expression through a HIF-1α-dependent mechanism. 87 When cells are unable to efficiently repair DNA damage, it leads to persistent lesions that may cause genomic instability and mutations (Figure 4A). CEdG is associated with single-strand DNA breaks and increased mutation frequency.…”

Section: ■ Mg-ages On Dna and Proteinmentioning

confidence: 99%

Section: Mg-ages On Nucleic Acids: Impact On Structure and Repairmentioning

confidence: 99%

“… 87 The authors suggested that high glucose may downregulate NER protein expression through a HIF-1α-dependent mechanism. 87 …”

Section: Mg-ages On Nucleic Acids: Impact On Structure and Repairmentioning

confidence: 99%

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Methylglyoxal and Its Adducts: Induction, Repair, and Association with Disease

Lai

Gonzalez

Zoukari

et al. 2022

Chem. Res. Toxicol.

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Metabolism is an essential part of life that provides energy for cell growth. During metabolic flux, reactive electrophiles are produced that covalently modify macromolecules, leading to detrimental cellular effects. Methylglyoxal (MG) is an abundant electrophile formed from lipid, protein, and glucose metabolism at intracellular levels of 1–4 μM. MG covalently modifies DNA, RNA, and protein, forming advanced glycation end products (MG-AGEs). MG and MG-AGEs are associated with the onset and progression of many pathologies including diabetes, cancer, and liver and kidney disease. Regulating MG and MG-AGEs is a potential strategy to prevent disease, and they may also have utility as biomarkers to predict disease risk, onset, and progression. Here, we review recent advances and knowledge surrounding MG, including its production and elimination, mechanisms of MG-AGEs formation, the physiological impact of MG and MG-AGEs in disease onset and progression, and the latter in the context of its receptor RAGE. We also discuss methods for measuring MG and MG-AGEs and their clinical application as prognostic biomarkers to allow for early detection and intervention prior to disease onset. Finally, we consider relevant clinical applications and current therapeutic strategies aimed at targeting MG, MG-AGEs, and RAGE to ultimately improve patient outcomes.

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Section: Mg-protein Adducts: Formation and Impact On Structure And Fu...mentioning

confidence: 95%

Section: ■ Mg-ages On Dna and Proteinmentioning

confidence: 99%

Section: ■ Mg-ages On Dna and Proteinmentioning

confidence: 99%

Section: Mg-ages On Nucleic Acids: Impact On Structure and Repairmentioning

confidence: 99%

“… 87 The authors suggested that high glucose may downregulate NER protein expression through a HIF-1α-dependent mechanism. 87 …”

Section: Mg-ages On Nucleic Acids: Impact On Structure and Repairmentioning

confidence: 99%

See 3 more Smart Citations

Methylglyoxal and Its Adducts: Induction, Repair, and Association with Disease

Lai

Gonzalez

Zoukari

et al. 2022

Chem. Res. Toxicol.

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Cellular senescence in cancer: molecular mechanisms and therapeutic targets

Jin,

Duan,

et al. 2024

MedComm

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Aging exhibits several hallmarks in common with cancer, such as cellular senescence, dysbiosis, inflammation, genomic instability, and epigenetic changes. In recent decades, research into the role of cellular senescence on tumor progression has received widespread attention. While how senescence limits the course of cancer is well established, senescence has also been found to promote certain malignant phenotypes. The tumor‐promoting effect of senescence is mainly elicited by a senescence‐associated secretory phenotype, which facilitates the interaction of senescent tumor cells with their surroundings. Targeting senescent cells therefore offers a promising technique for cancer therapy. Drugs that pharmacologically restore the normal function of senescent cells or eliminate them would assist in reestablishing homeostasis of cell signaling. Here, we describe cell senescence, its occurrence, phenotype, and impact on tumor biology. A “one‐two‐punch” therapeutic strategy in which cancer cell senescence is first induced, followed by the use of senotherapeutics for eliminating the senescent cells is introduced. The advances in the application of senotherapeutics for targeting senescent cells to assist cancer treatment are outlined, with an emphasis on drug categories, and the strategies for their screening, design, and efficient targeting. This work will foster a thorough comprehension and encourage additional research within this field.

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