A two-photon fluorescent probe for ratiometric imaging of endogenous hypochlorous acid in live cells and tissues

Jun, Yong Woong; Sarkar, Sourav; Singha, Subhankar; Reo, Ye Jin; Kim, Hye Rim; Kim, Jong-Jin; Chang, Young‐Tae; Ahn, Kyo Han

doi:10.1039/c7cc05834a

Cited by 96 publications

(35 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…have been developed for imaging HClO in live cells (30)(31)(32)(33)(34)(35)(36). With these probes, visualization of HClO in wounded tissues or an inflammatory mouse model has been achieved (35,37). However, there has been no report on direct real-time visualization of HClO fluxes in the brain of live animals, especially during epileptic seizures.…”

Section: Significancementioning

confidence: 99%

Epileptic brain fluorescent imaging reveals apigenin can relieve the myeloperoxidase-mediated oxidative stress and inhibit ferroptosis

Shao

Yuan

Liu

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

118

View full text Add to dashboard Cite

Myeloperoxidase (MPO)-mediated oxidative stress has been suggested to play an important role in the pathological dysfunction of epileptic brains. However, there is currently no robust brain-imaging tool to detect real-time endogenous hypochlorite (HClO) generation by MPO or a fluorescent probe for rapid high-throughput screening of antiepileptic agents that control the MPO-mediated chlorination stress. Herein, we report an efficient two-photon fluorescence probe (named HCP) for the real-time detection of endogenous HClO signals generated by MPO in the brain of kainic acid (KA)-induced epileptic mice, where HClO-dependent chlorination of quinolone fluorophore gives the enhanced fluorescence response. With this probe, we visualized directly the endogenous HClO fluxes generated by the overexpression of MPO activity in vivo and ex vivo in mouse brains with epileptic behaviors. Notably, by using HCP, we have also constructed a high-throughput screening approach to rapidly screen the potential antiepileptic agents to control MPO-mediated oxidative stress. Moreover, from this screen, we identified that the flavonoid compound apigenin can relieve the MPO-mediated oxidative stress and inhibit the ferroptosis of neuronal cells. Overall, this work provides a versatile fluorescence tool for elucidating the role of HClO generation by MPO in the pathology of epileptic seizures and for rapidly discovering additional antiepileptic agents to prevent and treat epilepsy.

show abstract

Section: Significancementioning

confidence: 99%

Epileptic brain fluorescent imaging reveals apigenin can relieve the myeloperoxidase-mediated oxidative stress and inhibit ferroptosis

Shao

Yuan

Liu

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

118

View full text Add to dashboard Cite

show abstract

“…However, the detection of endogenous HOCl is a challenging task due to the low biological concentration, a short lifetime, and a strong oxidizing property [ 43 ]. In 2017, Ahn et al reported a benzo[ g ]coumarin-based ratiometric probe for endogenous HOCl imaging in live cells and tissues ( 31 ; Figure 10 ) [ 21 ]. An oxathiolane group is substituted at the electron-withdrawing position, and the deprotection into acetyl of this moiety by HOCl causes the intramolecular charge-transfer (ICT) character change of the benzo[ g ]coumarin dye in a ratiometric manner: emission maximum shift from 598 nm (with 424 nm absorption maximum) to 633 nm (with 598 nm absorption maximum).…”

Section: Benzo[ G ]Coumarins For Fluorescent Prmentioning

confidence: 99%

Benzo[g]coumarin-Based Fluorescent Probes for Bioimaging Applications

Jung

Huh

et al. 2018

Journal of Analytical Methods in Chemistry

View full text Add to dashboard Cite

Benzo[g]coumarins, which consist of coumarins fused with other aromatic units in the linear shape, have recently emerged as an interesting fluorophore in the bioimaging research. The pi-extended skeleton with the presence of electron-donating and electron-withdrawing substituents from the parent coumarins changes the basic photophysical parameters such as absorption and fluorescence emission significantly. Most of the benzo[g]coumarin analogues show red/far-red fluorescence emission with high two-photon absorbing property that can be applicable for the two-photon microscopy (TPM) imaging. In this review, we summarized the recently developed benzo[g]coumarin analogues including photophysical properties, synthesis, and applications for molecular probes that can sense biologically important species such as metal ions, cell organs, reactive species, and disease biomarkers.

show abstract

“…The probe based on the red-emitting acetyl-benzocoumarin (AcBC) dye wiithin the probe, oxathiolane group was attached in orderf or it to react with HOCl. [127] Reaction with HOCl will trigger the ring opening reactiono ft hiolactone and whichi nvolves ar atiometric fluorescencec hange only toward HOCl along with high sensitivity.F urther studies reveal that the probe can be used to image HOCl in living HeLa cells.…”

Section: Scheme115 Anthracene Basedp Robe For Hocl Detectionmentioning

confidence: 99%

“…The Ahn group in 2017 developed a fluorescent probe that enables ratiometric imaging of endogenous hypochlorous acid (HOCl) in cells and tissues by way of two‐photon microscopy (Scheme ). The probe based on the red‐emitting acetyl‐benzocoumarin (AcBC) dye wiithin the probe, oxathiolane group was attached in order for it to react with HOCl . Reaction with HOCl will trigger the ring opening reaction of thiolactone and which involves a ratiometric fluorescence change only toward HOCl along with high sensitivity.…”

Section: Introductionmentioning

confidence: 99%

Imaging of Hypochlorous Acid by Fluorescence and Applications in Biological Systems

Yudhistira

Mulay

Kim

et al. 2019

Chemistry An Asian Journal

View full text Add to dashboard Cite

In recent decades, HOCl research has attracted a lot of scientists from around the world. This chemical species is well known as an important player in the biological systems of eukaryotic organisms including humans. In the human body, HOCl is produced by the myeloperoxidase enzyme from superoxide in very low concentrations (20 to 400 μm); this species is secreted by neutrophils and monocytes to help fight pathogens. However, in the condition called “oxidative stress”, HOCl has the capability to attack many important biomolecules such as amino acids, proteins, nucleotides, nucleic acids, carbohydrates, and lipids; these reactions could ultimately contribute to a number of diseases such as neurodegenerative diseases (AD, PD, and ALS), cardiovascular diseases, and diabetes. In this review, we discuss recent efforts by scientists to synthesize various fluorophores which are attached to receptors to detect HOCl such as: chalcogen‐based oxidation, oxidation of 4‐methoxyphenol, oxime/imine, lactone ring opening, and hydrazine. These synthetic molecules, involving rational synthetic pathways, allow us to chemoselectively target HOCl and to study the level of HOCl selectivity through emission responses. Virtually all the reports here deal with well‐defined and small synthetic molecular systems. A large number of published compounds have been reported over the past years; this growing field has given scientists new insights regarding the design of the chemosensors. Reversibility, for example is considered important from the stand point of chemosensor reuse within the biological system; facile regenerability using secondary analytes to obtain the initial probe is a very promising avenue. Another aspect which is also important is the energy of the emission wavelength of the sensor; near‐infrared (NIR) emission is favorable to prevent autofluorescence and harmful irradiation of tissue; thus, extended applicability of such sensors can be made to the mouse model or animal model to help image internal organs. In this review, we describe several well‐known types of receptors that are covalently attached to the fluorophore to detect HOCl. We also discuss the common fluorophores which are used by chemist to detect HOCl, Apart from the chemical aspects, we also discuss the capabilities of the compounds to detect HOCl in living cells as measured through confocal imaging. The growing insight from HOCl probing suggests that there is still much room for improvement regarding the available molecular designs, knowledge of interplay between analytes, biological applicability, biological targeting, and chemical switching, which can also serve to further sensor and theurapeutic agent development alike.

show abstract

A two-photon fluorescent probe for ratiometric imaging of endogenous hypochlorous acid in live cells and tissues

Cited by 96 publications

References 54 publications

Epileptic brain fluorescent imaging reveals apigenin can relieve the myeloperoxidase-mediated oxidative stress and inhibit ferroptosis

Epileptic brain fluorescent imaging reveals apigenin can relieve the myeloperoxidase-mediated oxidative stress and inhibit ferroptosis

Benzo[g]coumarin-Based Fluorescent Probes for Bioimaging Applications

Imaging of Hypochlorous Acid by Fluorescence and Applications in Biological Systems

Contact Info

Product

Resources

About