Peroxynitrite-mediated glyoxalase I epigenetic inhibition drives apoptosis in airway epithelial cells exposed to crystalline silica via a novel mechanism involving argpyrimidine-modified Hsp70, JNK, and NF-κB

Antognelli, Cinzia; Gambelunghe, Angela; Muzi, Giacomo; Talesa, Vincenzo Nicola

doi:10.1016/j.freeradbiomed.2015.03.026

Cited by 32 publications

(43 citation statements)

References 82 publications

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“…Furthermore, only MI affected the expression of antioxidant proteins such as aldehyde dehydrogenase (ALDH1A1) and peroxiredoxin‐6 (PRDX6), which are known to protect cells from apoptotic cell death (Luo et al ., ; Zha et al ., ). These results suggested that the MI exposures might be triggering oxidative stress pathways as MI has been reported to cause oxidative stress and apoptosis in human bronchial epithelial cells (Antognelli et al ., ).…”

Section: Discussionmentioning

confidence: 97%

Responses of A549 human lung epithelial cells to cristobalite and α-quartz exposures assessed by toxicoproteomics and gene expression analysis

et al. 2016

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In this study, we used cytotoxicity assays, proteomic and gene expression analyses to examine the difference in response of A549 cells to two silica particles that differ in physical properties, namely cristobalite (CR) and α‐quartz (Min‐U‐Sil 5, MI). Cytotoxicity assays such as lactate dehydrogenase release, 5‐bromo‐2′‐deoxyuridine incorporation and cellular ATP showed that both silica particles could cause cell death, decreased cell proliferation and metabolism in the A549 human lung epithelial cells. While cytotoxicity assays revealed little difference between CR and MI exposures, proteomic and gene expression analyses unveiled both similar and unique molecular changes in A549 cells. For instance, two‐dimensional gel electrophoresis data indicated that the expression of proteins in the cell death (e.g., ALDH1A1, HTRA2 and PRDX6) and cell proliferation (e.g., FSCN1, HNRNPAB and PGK1) pathways were significantly different between the two silica particles. Reverse transcription–polymerase chain reaction data provided additional evidence supporting the proteomic findings. Preliminary assessment of the physical differences between CR and MI suggested that the extent of surface interaction between particles and cells could explain some of the observed biological effects. However, the differential dose–response curves for some other genes and proteins suggest that other physical attributes of particulate matter can also contribute to particulate matter‐related cellular toxicity. Our results demonstrated that toxicoproteomic and gene expression analyses are sensitive in distinguishing subtle toxicity differences associated with silica particles of varying physical properties compared to traditional cytotoxicity endpoints. Copyright © 2016 Her Majesty the Queen in Right of Canada. Journal of Applied Toxicology published by John Wiley & Sons, Ltd.

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Section: Discussionmentioning

confidence: 97%

Responses of A549 human lung epithelial cells to cristobalite and α-quartz exposures assessed by toxicoproteomics and gene expression analysis

et al. 2016

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“…Total protein extracts were prepared by lysing the cells (4 C) in radioimmunoprecipitation assay lysis buffer. 29 For subcellular fractionation, cells were resuspended in Mitobuffer. 29 Protein concentration in cell extracts was determined using the Pierce BCA Protein Assay Kit (Thermo Fisher Scientific), by reference to a standard curve prepared using dilutions of bovine serum albumin.…”

Section: Protein Extraction and Western Blot Analysismentioning

confidence: 99%

“…The activity of Glo1 was assessed as previously described in lysates from cell lines. 28,29 Glo1 activity was assayed according to Mannervik et al 44 Briefly, the assay solution contained 0.1 mol/L sodium phosphate buffer (pH 7.2), 2 mmol/L MG, and 1 mmol/L GSH. The reaction was monitored spectrophotometrically by following the increase in absorbance at 240 nm and 25 C. One unit of activity was defined as 1 mmol of S-D-lactoylglutathione produced per minute.…”

Section: Glo1 Enzyme Activitymentioning

confidence: 99%

“…Apoptosis was detected by evaluating caspase 3 activation, using an enzyme-linked immunosorbent assay (ELISA) kit (Invitrogen, Milan, Italy), specific for activated human Caspase-3 following the manufacturer's instructions, as well as by DNA fragmentation by agarose gel electrophoresis. 28,29 Gene Silencing Glo1 silencing was performed as previously described. 23,27 Briefly, cells were transiently transfected with a pool of four siRNA oligonucleotides targeting Glo1 (ON-TARGET plus SMART pool siRNA) or with a pool of nontargeting siRNA oligonucleotides (siCtr) (ON-TARGET plus siCONTROL) to exclude off-target effects (all from Dharmacon RNA Technologies, Carlo Erba, Milan, Italy), using DharmaFECT 2 transfection reagent (Dharmacon RNA Technologies, Carlo Erba, Milan, Italy), according to the manufacturer's instructions and as previously described.…”

Section: Apoptosis Detectionmentioning

confidence: 99%

“…25e32 By using the cofactor glutathione (GSH), Glo1 prevents the accumulation of MG, thereby suppressing dicarbonyl-mediated glycation reactions. More importantly, Glo1 overexpression decreases accumulation of AGEs in Caenorhabditis elegans, 33 diabetic rats, 34 and human cells, 29,32 and Glo1 knockdown induces the intracellular accumulation of MG-derived AGEs. 25e27,32,35 Therefore, Glo1, by preventing the onset of MG-dependent carbonyl stress leading to apoptosis, is a key antiglycation defense that sustains cell viability.…”

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confidence: 93%

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Testosterone and Follicle Stimulating Hormone–Dependent Glyoxalase 1 Up-Regulation Sustains the Viability of Porcine Sertoli Cells through the Control of Hydroimidazolone– and Argpyrimidine-Mediated NF-κB Pathway

Antognelli

Mancuso

Frosini

et al. 2018

The American Journal of Pathology

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Because Sertoli cells (SCs) play a central role in germ cell survival, their death may result in marked germ cell loss and infertility. SCs are the only somatic cells within the seminiferous tubules and are essential for regulating spermatogenesis. Factors that enhance or diminish the viability of SCs may have profound effects on spermatogenesis. Yet the mechanisms underlying the maintenance of SC viability remain largely unknown. Glyoxalase 1 (Glo1) detoxifies methylglyoxal (MG), a highly reactive carbonyl species mainly formed during glycolysis, which is a potent precursor of cytotoxic advanced glycation end products (AGEs). Hydroimidazolone (MG-H1) and argpyrimidine (ArgPyr) are AGEs resulting from MG-mediated post-translational modification of arginine residues in various proteins. The role of Glo1 and MG-derived AGEs in regulating the fate of SCs has never been investigated. By using gene silencing and the specific MG scavenger, aminoguanidine, the authors demonstrate that Glo1, under testosterone and follicle-stimulating hormone control, sustains viability of porcine neonatal SCs through a mechanism involving the NF-κB pathway. Glo1 knockdown induces a mitochondrial apoptotic pathway driven by the intracellular accumulation of MG-H1 and ArgPyr that desensitizes NF-κB signaling by modifying the inhibitor of NF-κB kinase, IKKß. This is the first report describing a role for Glo1 and MG-derived AGEs in SC biology, providing valuable new insights into the potential involvement of this metabolic axis into spermatogenesis.

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Argpyrimidine bonded to RAGE regulates autophagy and cell cycle to cause periodontal destruction

Dong

Gao

et al. 2022

Journal Cellular Physiology

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Argpyrimidine (APMD), a methylglyoxal-arginine-derived product, is one of the main products of diabetes mellitus. We aimed to systematically investigate the role of APMD in regulating autophagy activity, with a specific focus on the finding of APDM binding molecule, matching amino acid residues, autophagy flux and proteins, cell cycle arrest, cell skeleton and migration, PI3K/AKT/mTOR pathways, inflammatory signals, alveolar bone destruction, and inhibition verification. In this study, binding to 59/94/121 amino acid residues of advanced glycosylation end product receptor (RAGE), APMD suppressed PI3K/AKT/mTOR pathway to attenuate cell survival of periodontal ligament cells (PDLCs). Simultaneously, autophagy proteins ATG5, Beclin1, and LC3-II/I expression ratio were upregulated while P62/SQSTM was downregulated. Cell cycle arrested at G0/G1 with enhancing Cyclin D1/CDK4 and decreasing Cyclin A/CDK2 expression. Inhibition of autophagy abrogated APMDinduced cell cycle arrest. Furthermore, the inflammation regulation network of matrix metalloproteinase (MMP)-2, MMP-9, MAPKs and NF-κB pathways were activated by APMD. Rat periodontal models confirmed that APMD induced alveolar bone resorption, increased inflammatory infiltrates, and degraded collagen fibers through RAGE and PI3K. APMD-induced autophagy, G0/G1 arrest, proinflammatory signals activating and periodontal destruction were reversed by RAGE knockdown while aggravated by PI3K inhibitor. This study provides the first evidence that APMD bind to RAGE to regulate autophagy and cell cycle of PDLCs through the PI3K/AKT/mTOR pathway, thereby promoting periodontal destruction.

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Peroxynitrite-mediated glyoxalase I epigenetic inhibition drives apoptosis in airway epithelial cells exposed to crystalline silica via a novel mechanism involving argpyrimidine-modified Hsp70, JNK, and NF-κB

Cited by 32 publications

References 82 publications

Responses of A549 human lung epithelial cells to cristobalite and α-quartz exposures assessed by toxicoproteomics and gene expression analysis

Responses of A549 human lung epithelial cells to cristobalite and α-quartz exposures assessed by toxicoproteomics and gene expression analysis

Testosterone and Follicle Stimulating Hormone–Dependent Glyoxalase 1 Up-Regulation Sustains the Viability of Porcine Sertoli Cells through the Control of Hydroimidazolone– and Argpyrimidine-Mediated NF-κB Pathway

Argpyrimidine bonded to RAGE regulates autophagy and cell cycle to cause periodontal destruction

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