Nε-(1-Carboxymethyl)-L-lysine is a unique post-translational modification (PTM) of proteins that is generated by the non-enzymatic glycation of lysine residues [2]. The levels of CML in peripheral blood and circulating extracellular vesicles (EVs) can distinguish between early and middle-stage Alzheimer's disease[2]. Nε-(1-Carboxymethyl)-L-lysine has been employed as a pertinent marker that reflects the occurrence and level of process-induced AGEs in food or of those endogenously formed[3].
In vitro, Nε-(1-Carboxymethyl)-L-lysine treatment at 50μM for 24 hours enhanced the expression of cancer stem cell markers in JJ012 cells, leading to the activation of the RAGE/NF-κB signaling pathway and the inhibition of the AKT signaling pathway[4]. Treatment with 10μM Nε-(1-Carboxymethyl)-L-lysine and 15mM D-glucose for 6 days significantly increased the mRNA expression of G6Pase in LO2 liver cells, decreased the phosphorylation level of AMPK, and promoted cellular lipid biosynthesis and fatty acid β-oxidation[5]. Treatment of U2OS cells with 50μM Nε-(1-Carboxymethyl)-L-lysine for 24 hours induced cell migration and invasion, and stimulated the expression of RAGE, ERK and NFκB[6].
References:
[1] Fu M X, Requena J R, Jenkins A J, et al. The advanced glycation end product, N∊-(Carboxymethyl) lysine, is a product of both lipid peroxidation and glycoxidation reactions (∗)[J]. Journal of Biological Chemistry, 1996, 271(17): 9982-9986.
[2] Haddad M, Perrotte M, Landri S, et al. Circulating and extracellular vesicles levels of N-(1-Carboxymethyl)-L-Lysine (CML) differentiate early to moderate Alzheimer’s disease[J]. Journal of Alzheimer’s Disease, 2019, 69(3): 751-762.
[3] Tareke E, Forslund A, Lindh C H, et al. Isotope dilution ESI-LC-MS/MS for quantification of free and total Nε-(1-Carboxymethyl)-l-Lysine and free Nε-(1-Carboxyethyl)-l-Lysine: Comparison of total Nε-(1-Carboxymethyl)-l-Lysine levels measured with new method to ELISA assay in gruel samples[J]. Food Chemistry, 2013, 141(4): 4253-4259.
[4] Chang T Y, Lan K C, Wu C H, et al. Nε-(1-Carboxymethyl)-L-lysine, an advanced glycation end product, exerts malignancy on chondrosarcoma via the activation of cancer stemness[J]. Archives of Toxicology, 2023, 97(8): 2231-2244.
[5] Wu Y, Wu Y, Zhang Z, et al. N ε-(Carboxymethyl) lysine (CML) Promotes Disorders of Glucose and Lipid Metabolism in Human Hepatic LO2 Cells[J]. ACS Food Science & Technology, 2023, 3(10): 1635-1645.
[6] Chang T Y, Lan K C, Wu C H, et al. Nε-(1-carboxymethyl)-L-lysine/RAGE signaling drives metastasis and cancer stemness through ERK/NFκB axis in osteosarcoma[J]. International Journal of Biological Sciences, 2024, 20(3): 880.
Nε-(1-Carboxymethyl)-L-lysine是一种独特的蛋白质翻译后修饰（PTM），由赖氨酸残基的非酶糖基化反应产生[1]。外周血和循环细胞外囊泡（EVs）中Nε-(1-Carboxymethyl)-L-lysine的水平能够区分早期和中期阿尔茨海默病[2]。Nε-(1-Carboxymethyl)-L-lysine已被用作一个相关标志物，用于反映食品中加工诱导的AGEs或内源性形成的AGEs的发生和水平[2]。
在体外，使用50μM的Nε-(1-Carboxymethyl)-L-lysine处理JJ012细胞24小时，增强了癌症干细胞标志物的表达，导致RAGE/NF-κB信号通路激活以及AKT信号通路抑制[4]。使用10μM的Nε-(1-Carboxymethyl)-L-lysine和15mM的D-葡萄糖处理LO2肝细胞6天，显著增加了G6Pase的mRNA表达，降低了AMPK的磷酸化水平，并促进了细胞脂质生物合成和脂肪酸β-氧化[5]。使用50μM的Nε-(1-Carboxymethyl)-L-lysine处理U2OS细胞24小时，诱导了细胞迁移和侵袭，并刺激了RAGE、ERK和NFκB的表达[6]。