Reversible Reaction-Based Fluorescent Probe for Real-Time Imaging of Glutathione Dynamics in Mitochondria

Chen, Jianwei; Jiang, Xiqian; Zhang, Chengwei; MacKenzie, Kevin R.; Stossi, Fabio; Palzkill, Timothy; Wang, Meng C.; Wang, Jin

doi:10.1021/acssensors.7b00425

Cited by 102 publications

(62 citation statements)

References 17 publications

(36 reference statements)

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“…Moreover, reformation of probe 1 via a retro‐Michael process was further confirmed by RP‐HPLC experiments (see the Supporting Information). It is worth noting that probes based on reversible thio‐Michael additions have recently been reported to monitor dynamic biological processes, but such probes are still rare in the literature …”

Section: Resultsmentioning

confidence: 99%

Detection of Biothiols with a Fast‐Responsive and Water‐Soluble Pyrazolone‐Based Fluorogenic Probe

2018

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Non‐protein thiols such as GSH, Hcy, or Cys, are present at different concentration levels in the body depending on the thiol species and their localization (plasma, cell, urine etc···). They play vital roles in controlling redox‐mediated biological processes, and abnormal levels of biothiols are related to a variety of syndromes. In few years, fluorometric methods have gain increasing attention enabling a rapid, sensitive and spatiotemporal detection of biothiols. Herein, is reported a novel two‐step access to a water‐soluble fluorogenic probe based on the 7‐aminocoumarin dye conjugated to a pyrazolone moiety. Upon the addition of biothiols, the fluorescence is turned‐on at 485 nm by a reversible thio‐Michael addition process, which enables the detection of biothiols in the low nanomolar range.

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Section: Resultsmentioning

confidence: 99%

Detection of Biothiols with a Fast‐Responsive and Water‐Soluble Pyrazolone‐Based Fluorogenic Probe

2018

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“…Based on this, they also reported a mitochondria-targetable probe 5 optimized just by substituting the two carboxylic acid groups in probe 5 with a triphenylphosphium group connected with a 4-carbon linker. [14] Probe 5 responds to both the increases and decreases of GSH levels with fast reaction rates accompanied by the same ratiometric fluorescence response as probe 4.…”

Section: Eurjocmentioning

confidence: 93%

Reversible Reaction‐Based Fluorescent Probes for Dynamic Sensing and Bioimaging

2020

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Diverse chemical species such as ions and molecules exist within living cells and organisms undergoing dynamic changes in their local environment by a web of continuously interacting reactions. Reaction‐based fluorescent probes with a highly sought reversible feature can provide a real‐time monitor of the concentration dynamics (increases and decreases) of such chemical species, thus ideally suited to understand the physiological function, and pathogenic mechanisms of corresponding bio‐species in the regulation of cellular function and disease progression. This review summarizes the current methods for constructing reversible reaction‐based fluorescent probes. The sensing mechanisms and biological applications of these probes are also discussed. The representative examples reported recently are categorized according to the type of reversible chemical reactions utilized: nucleophilic additions (Michael additions, chromophore reactions), nucleophilic addition‐condensation reactions, and redox reactions. Finally, we present the potential challenges and suggestions for developing probes based on dynamic and reversible covalent bond formation reactions.

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“…The mitochondrion is probably the most studied eukaryotic cellular subcompartment due to its indispensable role in the regulation of cellular metabolism and multifaceted functions associated with various diseases, such as cancer, neurodegenerative diseases, and diabetes [1][2][3]. Even though each cellular compartment is significant, the mitochondrion is an all-rounder carrying multiple responsibilities including apoptosis (intrinsic) regulation, energy production, respiratory cycle, amino acid metabolism, and redox signaling [4][5][6]. On the one hand, mitochondrion produces ATP (adenosine triphosphate) for cell survival, while, on the other hand, controlling lethal functions, such as apoptosis and necrosis [7,8].…”

Section: Introductionmentioning

confidence: 99%

Recent Progress in Mitochondria-Targeted Drug and Drug-Free Agents for Cancer Therapy

Jeena

Kim

Jin

et al. 2019

Cancers

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The mitochondrion is a dynamic eukaryotic organelle that controls lethal and vital functions of the cell. Being a critical center of metabolic activities and involved in many diseases, mitochondria have been attracting attention as a potential target for therapeutics, especially for cancer treatment. Structural and functional differences between healthy and cancerous mitochondria, such as membrane potential, respiratory rate, energy production pathway, and gene mutations, could be employed for the design of selective targeting systems for cancer mitochondria. A number of mitochondria-targeting compounds, including mitochondria-directed conventional drugs, mitochondrial proteins/metabolism-inhibiting agents, and mitochondria-targeted photosensitizers, have been discussed. Recently, certain drug-free approaches have been introduced as an alternative to induce selective cancer mitochondria dysfunction, such as intramitochondrial aggregation, self-assembly, and biomineralization. In this review, we discuss the recent progress in mitochondria-targeted cancer therapy from the conventional approach of drug/cytotoxic agent conjugates to advanced drug-free approaches.In healthy cells, mitochondria execute a controlled regulation of multiple functions to maintain the cellular growth-death cycle. However, in the case of tumor cells, to meet the higher metabolic demand of rapidly proliferating cells, dysregulation of mitochondrial metabolism occurs [14,15]. The difference between cancer cell mitochondria and normal cells includes several functional alterations, such as mutation of mtDNA that lead to OXPHOS (oxidative phosphorylation) inhibition and thus deficient respiration and ATP generation, mutation of mtDNA-encoded mitochondrial enzymes, such as SDH (succinate dehydrogenase), IDH1 (isocitrate dehydrogenase 1), IDH2 (isocitrate dehydrogenase 2) [16], and structural differences, such as higher membrane potential of cancer cell mitochondria and higher basicity inside the mitochondrial lumen. The evasion of cell death or inhibition of mitochondria-mediated apoptosis is a hallmark for cancer. Mitochondria generate ROS, which is necessary for signaling under normal conditions. However, when apoptosis is inhibited in the case of cancer, ROS contributes to the neoplastic transformation. Furthermore, for supporting tumor cell survival under harsh tumorigenic conditions, such as nutrient depletion and hypoxia, mitochondria provide flexibility in several pathways either by up-or downregulation [17]. This altered mitochondrial metabolism of cancer cells compared with that of their normal counterparts is advantageous for the selective targeting of cancer mitochondria in therapeutics, which focuses on the cancer mitochondria specific features [18]. Directing the therapeutic agent to the mitochondria is an efficient way of eliminating cancer cells because the designed drug molecules could act at the central point of the cell, and therefore, engineering mitochondrial-targeted therapeutic agents have gained much interest in cancer thera...

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Reversible Reaction-Based Fluorescent Probe for Real-Time Imaging of Glutathione Dynamics in Mitochondria

Cited by 102 publications

References 17 publications

Detection of Biothiols with a Fast‐Responsive and Water‐Soluble Pyrazolone‐Based Fluorogenic Probe

Detection of Biothiols with a Fast‐Responsive and Water‐Soluble Pyrazolone‐Based Fluorogenic Probe

Reversible Reaction‐Based Fluorescent Probes for Dynamic Sensing and Bioimaging

Recent Progress in Mitochondria-Targeted Drug and Drug-Free Agents for Cancer Therapy

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