Methylglyoxal-Dependent Glycative Stress Is Prevented by the Natural Antioxidant Oleuropein in Human Dental Pulp Stem Cells through Nrf2/Glo1 Pathway

Abstract

Methylglyoxal (MG) is a potent precursor of glycative stress (abnormal accumulation of advanced glycation end products, AGEs), a relevant condition underpinning the etiology of several diseases, including those of the oral cave. At present, synthetic agents able to trap MG are known; however, they have never been approved for clinical use because of their severe side effects. Hence, the search of bioactive natural scavengers remains a sector of strong research interest. Here, we investigated whether and how oleuropein (OP), the major bioactive component of olive leaf, was able to prevent MG-dependent glycative stress in human dental pulp stem cells (DPSCs). The cells were exposed to OP at 50 µM for 24 h prior to the administration of MG at 300 µM for additional 24 h. We found that OP prevented MG-induced glycative stress and DPSCs impairment by restoring the activity of Glyoxalase 1 (Glo1), the major detoxifying enzyme of MG, in a mechanism involving the redox-sensitive transcription factor Nrf2. Our results suggest that OP holds great promise for the development of preventive strategies for MG-derived AGEs-associated oral diseases and open new paths in research concerning additional studies on the protective potential of this secoiridoid.

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

“…Next, we investigated the effect of GOLD on the expression of NRF2 and GLO1 in mesangial cells. The NRF2/GLO1 signaling system is an important antioxidant activity signaling system [ 21 , 30 ]. As shown in Figure 4 A,C, GOLD significantly inhibited the expression of NRF2 and GLO1 in mesangial cells.…”

“…NRF2 is a key transcription factor that regulates genes involved in the antioxidant defense system. The expression of homeostasis regulators such as glyoxalase 1 (GLO1), which are regulated by NRF2, plays a role in preventing renal lesions from excessive inflammatory reactions through antioxidant reactions in mesangial cells [ 21 ]. NRF2 remains inactive while binding to Kelch-like ECH-associated protein 1 (KEAP1) in the cytoplasm [ 19 ].…”

Nanomechanical and molecular characterization of aging in dentinal collagen

“…In both crown and root dentin, we found a significant increase of MGO-derived AGEs in the >50yo group compared to <26yo patients ( Figure 1E ; p<0.05). Previous research has shown that MGO-derived AGEs accumulate in both the dental pulp and periodontal tissues (Retamal et al 2016; Delle Monache et al 2021), thus it is likely that perfusion from these tissues may promote MGO formation in dentin over time. Unlike bone, dentin has no turnover which facilitates the accumulation of AGEs in its organic matrix, similar to other slow turnover tissues such as tendons (Birch 2018).…”

Metastatic Prostate Cancer Cells Secrete Methylglyoxal-Derived MG-H1 to Reprogram Human Osteoblasts into a Dedifferentiated, Malignant-like Phenotype: A Possible Novel Player in Prostate Cancer Bone Metastases

“…The thermal cycling conditions were 1 cycle at 95 °C for 5 min followed by 45 cycles at 95 °C for 20 s and 60 °C for 30 s. Melting curves were performed for all of the primer pairs in standard conditions. Comparative analysis of gene expression was performed by means of the 2−(∆∆ C T) method [ 51 , 52 ].…”