Redox-Sensitive Glyoxalase 1 Up-Regulation Is Crucial for Protecting Human Lung Cells from Gold Nanoparticles Toxicity

Gambelunghe, Angela; Giovagnoli, Stefano; Michele, Alessandro Di; Boncompagni, Simona; DellʼOmo, Marco; Leopold, Kerstin; Iavicoli, Ivo; Talesa, Vincenzo Nicola; Antognelli, Cinzia

doi:10.3390/antiox9080697

Cited by 10 publications

(10 citation statements)

References 64 publications

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“…Thus, it is highly possible that the CA pre-treatment of INS-1 cells may increase Glo-1 protein expression and enzymatic activity via the Nrf2 signaling pathway. Similarly, the redox-dependent upregulation of Nrf2-mediated Glo-1 to protect human lung cells against gold nanoparticle-induced toxicity has been reported [33]. Human endothelial venous umbilical cells (HUVEC) treated with 10 µM CA prior to glyceraldehyde-induced AGEs treatment showed a substantial improvement in nuclear Nrf2 level through activation of extracellular signal-regulated kinase (ERK), and oral administration of 10 mg of CA/kg b.w.…”

Section: Discussionmentioning

confidence: 77%

Chebulic Acid Prevents Methylglyoxal-Induced Mitochondrial Dysfunction in INS-1 Pancreatic β-Cells

Yoo

Hong

et al. 2020

Antioxidants

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To investigate the anti-diabetic properties of chebulic acid (CA) associated with the prevention of methyl glyoxal (MG)-induced mitochondrial dysfunction in INS-1 pancreatic β-cells, INS-1 cells were pre-treated with CA (0.5, 1.0, and 2.0 μM) for 48 h and then treated with 2 mM MG for 8 h. The effects of CA and MG on INS-1 cells were evaluated using the following: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; glyoxalase 1 (Glo-1) expression via Western blot and enzyme activity assays; Nrf-2, nuclear factor erythroid 2-related factor 2 protein expression via Western blot assay; reactive oxygen species (ROS) production assay; mRNA expression of mitochondrial dysfunction related components (UCP2, uncoupling protein 2; VDAC1, voltage-dependent anion-selective channel-1; cyt c, cytochrome c via quantitative reverse transcriptase-PCR; mitochondrial membrane potential (MMP); adenosine triphosphate (ATP) synthesis; glucose-stimulated insulin secretion (GSIS) assay. The viability of INS-1 cells was maintained upon pre-treating with CA before exposure to MG. CA upregulated Glo-1 protein expression and enzyme activity in INS-1 cells and prevented MG-induced ROS production. Mitochondrial dysfunction was alleviated by CA pretreatment; this occurred via the downregulation of UCP2, VDAC1, and cyt c mRNA expression and the increase of MMP and ATP synthesis. Further, CA pre-treatment promoted the recovery from MG-induced decrease in GSIS. These results indicated that CA could be employed as a therapeutic agent in diabetes due to its ability to prevent MG-induced development of insulin sensitivity and oxidative stress-induced dysfunction of β-cells.

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Section: Discussionmentioning

confidence: 77%

Chebulic Acid Prevents Methylglyoxal-Induced Mitochondrial Dysfunction in INS-1 Pancreatic β-Cells

Yoo

Hong

et al. 2020

Antioxidants

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“…To clarify the molecular mechanism underlying MG-driven responses and OP preventive action, we investigated the possible involvement of Nrf2, the master redox-sensitive transcription factor that helps cells to adapt to oxidative stress and inflammation by inducing the expression of a large number of cytoprotective genes [ 38 ], including Glo1 [ 39 , 40 ] and those belonging to the vitagenes network, such as members of the Heat Shock Proteins (HSP) family Heme-oxygenase-1 (HO-1, Hsp70), thioredoxin (Trx), gamma-glutamylcysteine synthetase (γ-GCS) and superoxide dismutase (SOD) [ 41 ]. To this end, nuclear and cytoplasmic extracts of MG-treated DPSCs and controls were analyzed to examine the activation of Nrf2 by ELISA assessment of its nuclear translocation.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2021

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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.

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“…This directs NRF2 for degradation by the 26S proteasome [147,148]. Under oxidative stress, the complex dissociates and NRF2 translocates into the nucleus and upregulates several antioxidant genes, including those related to MG metabolism, as well as genes required for glutathione synthesis [149][150][151].…”

Section: Protective Role Of Nrf2 Against Glycation-derived Damage and Modulation Of Glo1mentioning

confidence: 99%

Glyoxalase System as a Therapeutic Target against Diabetic Retinopathy

et al. 2020

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Hyperglycemia, a defining characteristic of diabetes, combined with oxidative stress, results in the formation of advanced glycation end products (AGEs). AGEs are toxic compounds that have adverse effects on many tissues including the retina and lens. AGEs promote the formation of reactive oxygen species (ROS), which, in turn, boost the production of AGEs, resulting in positive feedback loops, a vicious cycle that compromises tissue fitness. Oxidative stress and the accumulation of AGEs are etiologically associated with the pathogenesis of multiple diseases including diabetic retinopathy (DR). DR is a devastating microvascular complication of diabetes mellitus and the leading cause of blindness in working-age adults. The onset and development of DR is multifactorial. Lowering AGEs accumulation may represent a potential therapeutic approach to slow this sight-threatening diabetic complication. To set DR in a physiological context, in this review we first describe relations between oxidative stress, formation of AGEs, and aging in several tissues of the eye, each of which is associated with a major age-related eye pathology. We summarize mechanisms of AGEs generation and anti-AGEs detoxifying systems. We specifically feature the potential of the glyoxalase system in the retina in the prevention of AGEs-associated damage linked to DR. We provide a comparative analysis of glyoxalase activity in different tissues from wild-type mice, supporting a major role for the glyoxalase system in the detoxification of AGEs in the retina, and present the manipulation of this system as a therapeutic strategy to prevent the onset of DR.

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Redox-Sensitive Glyoxalase 1 Up-Regulation Is Crucial for Protecting Human Lung Cells from Gold Nanoparticles Toxicity

Cited by 10 publications

References 64 publications

Chebulic Acid Prevents Methylglyoxal-Induced Mitochondrial Dysfunction in INS-1 Pancreatic β-Cells

Chebulic Acid Prevents Methylglyoxal-Induced Mitochondrial Dysfunction in INS-1 Pancreatic β-Cells

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

Glyoxalase System as a Therapeutic Target against Diabetic Retinopathy

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