Glyoxal-Lysine Dimer, an Advanced Glycation End Product, Induces Oxidative Damage and Inflammatory Response by Interacting with RAGE

Lee, Hee-Weon; Gu, Min; Kim, Yoon‐Sook; Lee, Jee Young; Lee, Seungju; Choi, In-Wook; Ha, Sang‐Keun

doi:10.3390/antiox10091486

Cited by 13 publications

(7 citation statements)

References 61 publications

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“…Recently, Lee et al made a similar finding in humans, demonstrating that in human mesangial cell lines, MG-AGEs trigger nephropathy via upregulating RAGE expression, leading to ROS production and activation of PI3K/AKT and NFκB . RAGE suppression via small-molecule inhibition and siRNA diminished oxidative stress and inflammatory response, suggesting the MG-AGE/RAGE axis contributes to nephrotic damage and dysfunction . This was also observed in rats with streptozotocin-induced nephropathy, in which treatment with Moutan Cortex mitigated AGE-induced inflammation, resulting in a protective effect .…”

Section: Physiological Impact Of Mg and Mg-agesmentioning

confidence: 61%

“… 214 RAGE suppression via small-molecule inhibition and siRNA diminished oxidative stress and inflammatory response, suggesting the MG-AGE/RAGE axis contributes to nephrotic damage and dysfunction. 215 This was also observed in rats with streptozotocin-induced nephropathy, in which treatment with Moutan Cortex mitigated AGE-induced inflammation, resulting in a protective effect. 216 MG-AGEs also act through the RAGE/JNK pathway, causing mitochondrial and ER stress dysfunction as well as an upregulation of apoptotic markers such as p53 and Bax.…”

Section: Physiological Impact Of Mg and Mg-agesmentioning

confidence: 75%

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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: Physiological Impact Of Mg and Mg-agesmentioning

confidence: 61%

Section: Physiological Impact Of Mg and Mg-agesmentioning

confidence: 75%

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

Lai

Gonzalez

Zoukari

et al. 2022

Chem. Res. Toxicol.

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“…RAGE acts as a key factor in transmitting AGEs and other associated signaling pathways 27 . Our obtained results showed that GO-AGEs treatment upregulated RAGE protein expression in HaCaT cells compared to that in the control group.…”

Section: Resultsmentioning

confidence: 99%

Glyoxal-derived advanced glycation end products (GO-AGEs) with UVB critically induce skin inflammaging: in vitro and in silico approaches

Sultana,

Parveen,

Kang

et al. 2024

Sci Rep

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Advanced glycation end products (AGEs) have potential implications on several diseases including skin inflammation and aging. AGEs formation can be triggered by several factors such as UVB, glyoxal and methylglyoxal etc. However, little attention has been paid to glyoxal-derived AGEs (GO-AGEs) and UVB-induced skin inflammaging, with none have investigated together. This study aimed to investigate the possible role of GO-AGEs and UVB in skin inflammaging focusing on revealing its molecular mechanisms. The effects of GO-AGEs in the presence or absence of UVB were studied by using enzyme linked immunosorbent assay, western blotting, qPCR, flow cytometry and in silico approaches. In HaCaT cells, GO-AGEs in the presence of UVB irradiation (125 mJ/cm2) dramatically enhanced the release of different pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) with further activation of RAGE signaling pathways (NF-κB, COX 2, and IL- 1β) and increased oxidative stress also noticed in NHEK cells. In NHDF cells, extracellular matrix disruption noted via increasing matrix metalloproteinase release and decreasing collagen type 1 and SIRT1 expression. Besides that, the docking scores obtained from the molecular docking study support the above-mentioned results. This study strongly suggests the pivotal role of GO-AGEs in skin inflammaging and illuminates novel molecular pathways for searching most effective and updated anti-aging therapy.

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“…Interestingly, mitochondrial transplantation was recently reported to modulate inflammation and apoptosis and alleviate tendinopathy. 36 Another study showed that combined SS-31 and mitochondrial transplantation were superior to either therapy alone for protecting against myocardial ischemia–reperfusion injury. 35 SS-31 has been shown to target cardiolipin, which is normally expressed only on the inner mitochondrial membrane.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of SS-31 as a Potential Strategy for Tendinopathy Treatment: An In Vitro Model

Zhang

et al. 2022

Am J Sports Med

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Background: Studies in our laboratory have demonstrated mitochondrial dysfunction in human and animal models of supraspinatus tendinopathy. SS-31 (elamipretide) has been reported to improve mitochondrial function and to be effective in clinical trials for several diseases. The potential of SS-31 in treating tendinopathy has not been explored. Hypothesis: SS-31 would improve mitochondrial function in human tenocytes sampled from patients with tendinopathy. Study Design: Controlled laboratory study. Methods: Healthy tenocytes were obtained from normal hamstring tendon biopsy specimens in 9 patients undergoing anterior cruciate ligament reconstruction, and tenocytes were collected from degenerative supraspinatus tendon biopsy specimens in 9 patients undergoing rotator cuff repair. Tenocytes were cultured, used at passage 1, and assigned to 4 groups: healthy tenocytes, healthy tenocytes with 1μM SS-31 treatment for 72 hours, degenerative tenocytes, and degenerative tenocytes with 1μM SS-31 treatment for 72 hours. The outcomes included measurements of mitochondrial potential, mitochondrial morphology by transmission electron microscopy imaging, reactive oxygen species and superoxidative dismutase activity, gene expression, and cell viability. Results: An increase in the cell fraction with depolarized mitochondria was found in degenerative tenocytes ( P = .014), followed by a decrease after SS-31 treatment ( P = .018). Transmission electron microscopy images demonstrated morphological changes with a decreased number and size of mitochondria per cell in the degenerative tenocytes ( P = .018) and with improvement after SS-31 treatment. There was no significant difference in the level of reactive oxygen species between healthy and degenerative tenocytes in culture, but superoxidative dismutase activity was significantly decreased in the degenerative group ( P = .006), which then increased after SS-31 treatment ( P = .012). These findings suggested that mitochondrial dysfunction may be reversed by SS-31 treatment. The gene expression of matrix metalloproteinase-1 (matrix remodeling, P = .029) and fatty acid–binding protein 4 (fatty infiltration, P = .046) was significantly upregulated in the degenerative tenocytes and reduced by SS-31 treatment ( P = .048; P = .007). Gene expression for hypoxia-inducible factor1 α and the proapoptotic regulator Bcl-2–associated X protein was increased in the degenerative tenocytes. There was a significant decrease in cell viability in degenerative tenocytes as compared with the healthy tenocytes, with small improvement after treatment with SS-31. Conclusion: There are changes in mitochondrial structure and function in tenocytes derived from degenerative tendons, and SS-31, as a mitochondrial protectant, could improve mitochondrial function and promote the healing of tendinopathy. Clinical Relevance: Mitochondrial dysfunction appears to play a role in the development of tendinopathy, and SS-31, as a mitochondrial protective agent, may be a therapeutic agent in the treatment of tendinopathy.

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Glyoxal-Lysine Dimer, an Advanced Glycation End Product, Induces Oxidative Damage and Inflammatory Response by Interacting with RAGE

Cited by 13 publications

References 61 publications

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

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

Glyoxal-derived advanced glycation end products (GO-AGEs) with UVB critically induce skin inflammaging: in vitro and in silico approaches

Evaluation of SS-31 as a Potential Strategy for Tendinopathy Treatment: An In Vitro Model

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