Modifications of Mitochondrial Function by Toxicants☆

Maruf, Abdullah Al; Lee, O.; O′Brien, Patricia J.

doi:10.1016/b978-0-12-801238-3.01900-0

Cited by 5 publications

(10 citation statements)

References 254 publications

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“…The addition of uric acid (500 μM) and SIN-1 (1.0 mM) led to a 0.32-fold decrease in the average green fluorescence intensity and 1.60-fold enhancement in the average red fluorescence intensity, when compared with the corresponding SIN-1 group (as determined by monitoring the green and red channels, respectively, Figure ). These results are consistent with suggestions in the literature that an increase in the ONOO – concentration can result in depletion of ATP …”

Section: Resultsmentioning

confidence: 95%

“…ROS and RNS are regarded as biomarkers in DILI and are thus analytes that have been frequently targeted using fluorescent probes. , Previous studies confirm that ATP production is decreased by exposure to APAP. ,, APAP-induced hepatoxicity was thus chosen as the model to investigate whether ATP-LW could detect ONOO – and ATP, since these two species could serve as early diagnostic biomarkers. Treatment of HL-7702 cells with APAP produced a marked increase in the fluorescence of the green channel and a significant decrease in the fluorescence in the red channel (Figure ).…”

Section: Resultsmentioning

confidence: 99%

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Dual-Channel Fluorescent Probe for the Simultaneous Monitoring of Peroxynitrite and Adenosine-5′-triphosphate in Cellular Applications

et al. 2021

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Changes in adenosine triphosphate (ATP) and peroxynitrite (ONOO − ) concentrations have been correlated in a number of diseases including ischemia-reperfusion injury and drug-induced liver injury. Herein, we report the development of a fluorescent probe ATP-LW, which enables the simultaneous detection of ONOO − and ATP. ONOO − selectively oxidizes the boronate pinacol ester of ATP-LW to afford the fluorescent 4-hydroxy-1,8-naphthalimide product NA-OH (λ ex = 450 nm, λ em = 562 nm or λ ex = 488 nm, λ em = 568 nm). In contrast, the binding of ATP to ATP-LW induces the spirolactam ring opening of rhodamine to afford a highly emissive product (λ ex = 520 nm, λ em = 587 nm). Due to the differences in emission between the ONOO − and ATP products, ATP-LW allows ONOO − levels to be monitored in the green channel (λ ex = 488 nm, λ em = 500−575 nm) and ATP concentrations in the red channel (λ ex = 514 nm, λ em = 575−650 nm). The use of ATP-LW as a combined ONOO − and ATP probe was demonstrated using hepatocytes (HL-7702 cells) in cellular imaging experiments. Treatment of HL-7702 cells with oligomycin A (an inhibitor of ATP synthase) resulted in a reduction of signal intensity in the red channel and an increase in that of the green channel as expected for a reduction in ATP concentrations. Similar fluorescence changes were seen in the presence of SIN-1 (an exogenous ONOO − donor).

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Section: Resultsmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

Dual-Channel Fluorescent Probe for the Simultaneous Monitoring of Peroxynitrite and Adenosine-5′-triphosphate in Cellular Applications

et al. 2021

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“…These results indicate that an increase of ONOO − can result in depletion of ATP, which is in agreement with previous studies. 22 We then set out to evaluate how imbalances in the energy metabolism instigated by obstructing ATP production can influence production of ONOO − . Oligomycin A inhibits ATP synthase by blocking its FO unit.…”

Section: Resultsmentioning

confidence: 99%

“…19,21 Previous studies confirm ATP production is decreased via APAP. 22,[42][43] APAP-induced hepatoxicity was chosen as the model for ATP-LW to investigate whether the two species can be regarded as early diagnostic biomarkers. Treatment of HL-7702 cells with APAP produced a marked increase in fluorescence in the green channel and significant decrease in fluorescence in the red channel (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…[19][20][21] Moreover, the model was selected because APAP can result in a depletion of ATP and an increase in the levels of ONOO − (Scheme S1). [22][23] It is important to note, we first disclosed our probe ATP-LW as a ChemRxiv preprint, 24 however, we felt that the paper could be substantially improved with the addition of biological experiments and so submission for publication of that paper was delayed. In order, to carry out those biological studies, we needed to resynthesize ATP-LW to fully evaluate the biological properties of our probe, however, the Covid-19 pandemic severely hindered our research progress.…”

Section: Introductionmentioning

confidence: 99%

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Dual-channel fluorescent probe for the simultaneous monitoring of peroxynitrite and adenosine-5’-triphosphate in cellular applications

Liu

Xue

et al. 2021

Preprint

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The concentrations of ATP and ONOO − have been correlated with the progression a number of diseases including ischemia-reperfusion injury and drug-induced liver injury. Here, we report the development of fluorescent probe, ATP-LW, which enables the simultaneous detection of ONOO − and ATP. ONOO − selectively oxidises the boronate pinacol ester of ATP-LW, to afford the fluorescent 4-hydroxy-1,8naphthalimide product NA-OH (λex = 450 nm, λem = 562 nm or λex = 488 nm, λem = 568 nm). While, the binding of ATP to ATP-LW induces the spirolactam ring opening of rhodamine to afford a highly emissive product (λex = 520 nm, λem = 587 nm). Due to the differences in emission between the ONOO − and ATP products, ATP-LW exhibits the unique ability to image ONOO − levels in the green channel (λex = 488 nm, λem = 500-575 nm) and ATP concentrations using the red channel (λex = 514 nm, λem = 575-650 nm). This was demonstrated using hepatocytes (HL-7702 cells) in cellular imaging experiments. The treatment of HL-7702 cell line with oligomycin A (an inhibitor of ATP synthase) resulted in a reduction of ATP in the red channel and increase in ONOO − green channel. While, the presence of SIN-1 (an exogenous ONOO − donor) results in an increase of ONOO − , and decrease in ATP. Significantly, when HL-7702 cells were treated with acetaminophen as a biological model for drug-induced liver injury, an increase in ONOO − green and decrease in ATP red channel fluorescence was observed. These results illustrate the utility of ATP-LW as a chemical tool to simultaneously monitor ATP and ONOO − concentrations in cellular-based applications.

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Targeting mitochondrial bioenergetics as a promising therapeutic strategy in metabolic and neurodegenerative diseases

Bhatti¹,

Gupta²,

Pahwa³

et al. 2022

Biomedical Journal

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Modifications of Mitochondrial Function by Toxicants☆

Cited by 5 publications

References 254 publications

Dual-Channel Fluorescent Probe for the Simultaneous Monitoring of Peroxynitrite and Adenosine-5′-triphosphate in Cellular Applications

Dual-Channel Fluorescent Probe for the Simultaneous Monitoring of Peroxynitrite and Adenosine-5′-triphosphate in Cellular Applications

Dual-channel fluorescent probe for the simultaneous monitoring of peroxynitrite and adenosine-5’-triphosphate in cellular applications

Targeting mitochondrial bioenergetics as a promising therapeutic strategy in metabolic and neurodegenerative diseases

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