Triethylene glycol dimethacrylate impairs bioenergetic functions and induces oxidative stress in mitochondria via inhibiting respiratory Complex I

Mikulás, Krisztina; Hermann, Péter; Gera, István; Komlódi, Tímea; Horváth, Gergő; Ambrus, Attila; Tretter, László

doi:10.1016/j.dental.2018.03.012

Cited by 15 publications

(15 citation statements)

References 90 publications

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“…Studies on permeabilized DPSC affirmed our earlier observation, that oxidation of CI substrates (a-KG, pyruvate plus malate and glutamate plus malate) is sensitive to TEGDMA-mediated inhibition ( Figure 2 B–D). Contrary to that the results obtained in isolated mitochondria [ 48 ], in succinate supported permeabilized cells a small but statistically significant inhibition of oxygen consumption was observed ( Figure 2 A). A possible explanation of this controversy could be the incomplete permeabilization of the cell membrane and the consequent imperfect wash out of CI substrates which could “contaminate” the oxidation of succinate via their high sensitivity to TEGDMA-mediated inhibition.…”

Section: Discussioncontrasting

confidence: 99%

“…It has been observed that TEGDMA inhibits mitochondrial O 2 consumption at the CI level [48]. In line with that study, our present results confirm the mitochondrial targets of TEGDMA, mainly the vulnerability of CI.…”

Section: Effects Of Tegdma and Mb On Bioenergetics Of Isolated Mitochsupporting

confidence: 93%

“…It was reported that TEGDMA adversely affects cellular metabolism, signaling, differentiation, and dentinogenesis, while it also interferes with wound healing and tissue repair [28,40,[68][69][70][71]; it induces oxidative stress [46][47][48], apoptosis and/or necrosis [42,43,49,72]. Due to its amphiphilic character, TEGDMA can penetrate the membranes of human gingival fibroblast and human oral epithelium of the mouth, resulting in an inflammatory response [73].…”

Section: Discussionmentioning

confidence: 99%

“…It was reported earlier that TEGDMA exhibited some of these deleterious effects via mitochondrial impairment [45][46][47][48][49].…”

Section: Introductionmentioning

confidence: 99%

“…In our previous report, using isolated mitochondria, we identified Complex I (CI) of the mitochondrial electron transport system, as a target of TEGDMA [48]. TEGDMA inhibited the CI-dependent O 2 consumption, which resulted in the depolarization of the mitochondrial membrane.…”

Section: Introductionmentioning

confidence: 99%

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Bioenergetic Impairment of Triethylene Glycol Dimethacrylate- (TEGDMA-) Treated Dental Pulp Stem Cells (DPSCs) and Isolated Brain Mitochondria are Amended by Redox Compound Methylene Blue

et al. 2020

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Background: Triethylene glycol dimethacrylate (TEGDMA) monomers released from resin matrix are toxic to dental pulp cells, induce apoptosis, oxidative stress and decrease viability. Recently, mitochondrial complex I (CI) was identified as a potential target of TEGDMA. In isolated mitochondria supported by CI, substrates oxidation and ATP synthesis were inhibited, reactive oxygen species production was stimulated. Contrary to that, respiratory Complex II was not impaired by TEGDMA. The beneficial effects of electron carrier compound methylene blue (MB) are proven in many disease models where mitochondrial involvement has been detected. In the present study, the bioenergetic effects of MB on TEGDMA-treated isolated mitochondria and on human dental pulp stem cells (DPSC) were analyzed. Methods: Isolated mitochondria and DPSC were acutely exposed to low millimolar concentrations of TEGDMA and 2 μM concentration of MB. Mitochondrial and cellular respiration and glycolytic flux were measured by high resolution respirometry and by Seahorse XF extracellular analyzer. Mitochondrial membrane potential was measured fluorimetrically. Results: MB partially restored the mitochondrial oxidation, rescued membrane potential in isolated mitochondria and significantly increased the impaired cellular O2 consumption in the presence of TEGDMA. Conclusion: MB is able to protect against TEGDMA-induced CI damage, and might provide protective effects in resin monomer exposed cells.

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Section: Discussioncontrasting

confidence: 99%

Section: Effects Of Tegdma and Mb On Bioenergetics Of Isolated Mitochsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

“…It was reported earlier that TEGDMA exhibited some of these deleterious effects via mitochondrial impairment [45][46][47][48][49].…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bioenergetic Impairment of Triethylene Glycol Dimethacrylate- (TEGDMA-) Treated Dental Pulp Stem Cells (DPSCs) and Isolated Brain Mitochondria are Amended by Redox Compound Methylene Blue

et al. 2020

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Mining and characterization of oxidative stress‐related binding proteins of parthenolide in Xanthomonas oryzae pv. oryzae

Zhou

Liu

et al. 2022

Pest Management Science

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BACKGROUND: Lack of control agents and development of bacterial resistance are emergent problems in the chemical control of rice bacterial blight, therefore novel bactericides against Xanthomonas oryzae pv. oryzae (Xoo, the causal agent of rice bacterial blight) are urgently needed. We previously found that parthenolide (PTL) is a potential lead against Xoo, and PTL inhibits Xoo growth via oxidative stress. However, the mechanism of action of PTL against Xoo needs further elucidation.RESULTS: In this study, a biotinylated PTL probe was synthesized, and two important subunits in the respiratory chain (NuoF of complex I and SdhB of complex II) of Xoo were captured with the probe and identified with liquid chromatography tandem mass spectrometry (LC-MS/MS). The binding between them was verified with pull-down and drug affinity responsive target stability technologies. In addition, purified proteins of NuoF and SdhB greatly lowered the antibacterial activity of PTL, and PTL evidently inhibited the enzyme activities of complexes I and II. Moreover, knockout of nuoF and sdhB in Xoo caused elevated reactive oxygen species (ROS) levels and increased sensitivity to PTL. Furthermore, molecular simulations indicated that PTL may form covalent bonds with Cys105 and Cys187 in NuoF and Cys106 in SdhB.CONCLUSION: PTL can directly bind to NuoF and SdhB, which impairs the enzyme functions of complexes I and II in the respiratory chain, leading to ROS accumulation in Xoo. This study will provide deep insight into the mechanism of action of PTL against Xoo.

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Quaternary ammonium compound as antimicrobial agent in resin-based sealants

et al. 2019

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Triethylene glycol dimethacrylate impairs bioenergetic functions and induces oxidative stress in mitochondria via inhibiting respiratory Complex I

Cited by 15 publications

References 90 publications

Bioenergetic Impairment of Triethylene Glycol Dimethacrylate- (TEGDMA-) Treated Dental Pulp Stem Cells (DPSCs) and Isolated Brain Mitochondria are Amended by Redox Compound Methylene Blue

Bioenergetic Impairment of Triethylene Glycol Dimethacrylate- (TEGDMA-) Treated Dental Pulp Stem Cells (DPSCs) and Isolated Brain Mitochondria are Amended by Redox Compound Methylene Blue

Mining and characterization of oxidative stress‐related binding proteins of parthenolide in Xanthomonas oryzae pv. oryzae

Quaternary ammonium compound as antimicrobial agent in resin-based sealants

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