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1.
Commun Biol ; 2: 446, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31815201

RESUMO

Gaseous formaldehyde is an organic small molecule formed in the early stages of earth's evolution. Although toxic in high concentrations, formaldehyde plays an important role in cellular metabolism and, unexpectedly, is found even in the healthy brain. However, its pathophysiological functions in the brain are unknown. Here, we report that under physiological conditions, spatial learning activity elicits rapid formaldehyde generation from mitochondrial sarcosine dehydrogenase (SARDH). We find that elevated formaldehyde levels facilitate spatial memory formation by enhancing N-methyl-D-aspartate (NMDA) currents, but that high formaldehyde concentrations gradually inactivate the NMDA receptor by cross-linking NR1 subunits to NR2B via the C232 residue. We also report that in mice with aldehyde dehydrogenase-2 (ALDH2) knockout, formaldehyde accumulation due to hypofunctional ALDH2 impairs memory, consistent with observations of Alzheimer's disease patients. We also find that formaldehyde deficiency caused by mutation of the mitochondrial SARDH gene in children with sarcosinemia or in mice with Sardh deletion leads to cognitive deficits. Hence, we conclude that endogenous formaldehyde regulates learning and memory via the NMDA receptor.

3.
Anal Chem ; 91(16): 10723-10730, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31328500

RESUMO

Living systems contain a diverse array of molecules and ions undergoing dynamic changes by a web of interacting chemical reactions. Sulfur dioxide (SO2) and formaldehyde (FA) can be generated endogenously in living organisms to maintain their homeostasis, but aberrant production of these species is implicated with some critical diseases. The dynamic interaction between SO2 and FA on the overall health and disease of living organisms remains challenging to elucidate owing to a dearth of methods for monitoring dynamic fluctuation of these transient species. Herein, we present the rational design, synthesis, and photophysical property studies of the probe (CaP), the first reversible fluorescent probe for investigating the dynamics changes of SO2 and FA. Importantly, the highly desirable attributes of the robust probe CaP (such as ultrafast response to SO2 in less than 5 s, swift restoration by FA in less than 1 min) make it possible to reversibly monitor the dynamic fluctuation of endogenous SO2 and FA in real-time in living cells for the first time. Moreover, we demonstrate the utility of this unique probe to detect the fluctuations of SO2 and FA in living zebrafish and murine species. This work provides a powerful chemical tool for monitoring the dynamic interaction of endogenous SO2 and FA, which will pave an avenue for interrogating the intersecting correlation between SO2 and FA in health and disease states.

4.
Talanta ; 204: 868-874, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31357375

RESUMO

Viscosity is a key factor that determines the diffusion-controlled processes in biological systems. The matrix of mitochondria contains various enzymes and other proteins with high density, and the diffusion of which are severely restricted by the cristae, making it the most crowded place in the cells. Herein, we reported a new near-infrared probe NV-1 with increased Stokes shift for monitoring viscosity changes in mitochondria. A remarkable increase of the fluorescence was observed in glycerol compared with which was observed in methanol at 744 nm. The probe was applied for measuring viscosity changes not only in mitochondria, but also in vivo (in zebra fishes and mice).


Assuntos
Corantes Fluorescentes/química , Mitocôndrias/metabolismo , Animais , Cumarínicos/química , Cumarínicos/efeitos da radiação , Cumarínicos/toxicidade , Feminino , Corantes Fluorescentes/efeitos da radiação , Corantes Fluorescentes/toxicidade , Células HeLa , Humanos , Indóis/química , Indóis/efeitos da radiação , Indóis/toxicidade , Luz , Camundongos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Mitocôndrias/química , Imagem Óptica/métodos , Viscosidade , Peixe-Zebra
5.
Chem Soc Rev ; 48(15): 4036-4048, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31187789

RESUMO

Reactive carbonyl species (RCS) are involved not only in diverse physiological pathways but also in various pathological processes, including Alzheimer's disease, diabetes, cardiovascular disease, and other malignant diseases. Therefore, it is essential to develop a simple and sensitive technology which can be employed to selectively monitor RCS in living biological samples, such as living cells, tissues, and animals. The subtle changes in the concentration of RCS in organisms can be detected by this technique. In this review, the design strategies of the typical examples of RCS fluorescent probes are highlighted and discussed. These advanced RCS probes may set the foundation for biomedical research on dynamic real-time monitoring of RCS in living systems.


Assuntos
Desenho de Drogas , Corantes Fluorescentes/química , Imagem Óptica , Espécies Reativas de Oxigênio/análise , Corantes Fluorescentes/síntese química , Estrutura Molecular , Espécies Reativas de Oxigênio/metabolismo
6.
Ann Clin Biochem ; 56(2): 210-218, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30373389

RESUMO

BACKGROUND: Morning urine formaldehyde concentrations could predict the severe degree of dementia in patients with post-stroke dementia and Alzheimer's disease. However, the routinely available technique of high-performance liquid chromatography (HPLC) for detecting urine formaldehyde requires expensive and sophisticated equipment. METHODS: We established a fluorescence spectrophotometric method by using a formaldehyde-specific fluorescent probe-NaFA (λex/em = 430/543 nm). As a standard reference method, the same batch of urine samples was analysed by HPLC with a fluorescence detector (λex/em = 346/422 nm). Then we compared the limits of detection and the limits of quantization detected by these two methods and addressed the relationship between urine formaldehyde and human cognitive ability. The Mini-Mental State Examination (MMSE), Clinical Dementia Rating and Activities of Daily Living scale were used to evaluate cognition function in 30 Alzheimer's disease patients and 52 healthy age-matched controls. RESULTS: Limits of detection and limits of quantization (1.27 and 2.48 µM) of the NaFA probe method were more accurate than Fluo-HPLC (1.52 and 2.91 µM). There was no difference in the detected formaldehyde values within day and day-to-day. Notably, only 3/82 urine formaldehyde concentrations detected by NaFA probe were below zero, while 12/82 of the values analysed by Fluo-HPLC were abnormal. More importantly, there were negatively correlated between urine formaldehyde concentrations detected by NaFA probe and MMSE scores, but positively correlated with Clinical Dementia Rating scores in Alzheimer's disease patients. CONCLUSIONS: This detecting urine formaldehyde method by NaFA probe was more rapid, sensitive and accurate than Fluo-HPLC.


Assuntos
Doença de Alzheimer/urina , Formaldeído/urina , Limite de Detecção , Espectrometria de Fluorescência/métodos , Urinálise/métodos , Atividades Cotidianas , Idoso , Doença de Alzheimer/fisiopatologia , Estudos de Casos e Controles , Cognição , Feminino , Humanos , Masculino , Fatores de Tempo
7.
J Fluoresc ; 29(1): 155-163, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30417249

RESUMO

Methylglyoxal (MGO) is one of the most important active carbonyl compounds in living organisms. It is a metabolic by product of glycolysis. MGO participates in glycosylation of proteins and nucleic acids to trigger carbonyl stress, inducing pathological status and even exacerbateing the development of chronic degenerative diseases. In order to study the diseases caused by MGO, it is meaningful for us to develop methods that could efficiently detect MGO. In our work, a new two-photon fluorescent turn-on probe which named NP has been designed which was made up of naphthalimides dye as the two-photon fluorescent platform and the o-phenylenediamine as recognition site. When reacted with MGO, NP showed excellent sensitivity and selectivity. Based on the two-photon fluorescence imaging technology, NP has firstly successful application in living cells, tissues and zebrafish to detecting MGO.


Assuntos
Corantes Fluorescentes/química , Imagem Óptica , Fótons , Aldeído Pirúvico/química , Animais , Teoria da Densidade Funcional , Corantes Fluorescentes/síntese química , Células HeLa , Humanos , Estrutura Molecular , Aldeído Pirúvico/síntese química , Peixe-Zebra
8.
Commun Biol ; 2(1): 479, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31925302

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

9.
Spectrochim Acta A Mol Biomol Spectrosc ; 204: 770-776, 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30007884

RESUMO

Hypoxia conditions could increase the activity of intracellular nitroreductase (NTR) and lead to many malignant diseases. Therefore, monitoring the activity of NTR is of great significance to study the related diseases. Organelles play crucial roles in the metabolism of living cells. In these organelles, the endoplasmic reticulum (ER) possesses single membrane structure, and it is the largest organelle in the cell. ER performs the synthesis, processing and modification of proteins and lipid, stabilizing the intracellular Ca2+ concentration and other physiological functions in living cells. Therefore, it is of great significance to develop ER-target probes in living system. Toward this goal, a new endoplasmic reticulum-targeted two-photon fluorescence turn-on NTR probe Na-NTR-ER is designed and synthesized. Probe Na-NTR-ER has been proved to display high sensitivity (36 ng/mL) and selectivity to NTR. Particularly, probe Na-NTR-ER has been successfully applied for the monitoring of NTR in ER with a high the Pearson's colocalization coefficient as 0.90 in HeLa cells and cancerous mouse tissues up to the depth of 100 µm with significant fluorescence signals.


Assuntos
Retículo Endoplasmático/metabolismo , Corantes Fluorescentes/química , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Sondas Moleculares/química , Neoplasias/diagnóstico por imagem , Nitrorredutases/análise , Animais , Linhagem Celular Tumoral , Corantes Fluorescentes/metabolismo , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Sondas Moleculares/metabolismo , Nitrorredutases/química , Nitrorredutases/metabolismo , Ratos
10.
Spectrochim Acta A Mol Biomol Spectrosc ; 188: 197-201, 2018 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-28715686

RESUMO

The biological activity of nitroreductase (NTR) is closely related to biological hypoxia status in organisms. The development of effective methods for monitoring the activity of NTR is of great significance for medical diagnosis and tumor research. Toward this goal, we have developed a new aggregation-induced emission (AIE) fluorescence NTR probe TPE-HY used the tetraphenylethene as the fluorophore, and used the nitro group as the NTR recognition site. The probe TPE-HY has many excellent properties, including rapid response, AIE characteristics, high sensitivity and selectivity, and low cytotoxicity. Importantly, the probe TPE-HY is successfully applied to monitor endogenous NTR in living HeLa cells.


Assuntos
Corantes Fluorescentes/química , Nitrorredutases/metabolismo , Sobrevivência Celular , Corantes Fluorescentes/síntese química , Células HeLa , Humanos , Espectrometria de Fluorescência , Fatores de Tempo
11.
Anal Chem ; 90(1): 998-1005, 2018 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-29212319

RESUMO

Discrimination of live and dead cells is an important task in biological, pathological, medical, and pharmaceutical studies. In this work, we have developed a novel fluorescent probe DACA that can discriminate live and dead cells in a dual-color mode for the first time. DACA can stain dead cells with blue fluorescence peaked at 440 nm, while it can also label live cells with orange emission peaked at 570 nm. Compared with one-color fluorescent probes, such a dual-color probe can efficiently avoid false positive results from cellular autofluorescence and misleading signals brought by inhomogeneous staining, and thus can supply more accurate information in biological applications. By means of DACA, the health status of tumor cells pretreated by H2O2 and ultraviolet radiation has been successfully detected and imaged. Moreover, DACA and the hydrolyzed product exhibit excellent two-photon properties. Live and dead cells, as well as the zebrafishes, have been discriminated with dual emission colors under one- and two-photon microscope. These results demonstrate that DACA is a powerful tool for dual-color distinguishing live and dead cells in vitro and in vivo.


Assuntos
Benzopiranos/química , Corantes Fluorescentes/química , Animais , Benzopiranos/síntese química , Benzopiranos/toxicidade , Morte Celular , Rastreamento de Células , Cor , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Células HeLa , Humanos , Hidrólise , Raios Infravermelhos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Peixe-Zebra
12.
Sci Rep ; 7(1): 12944, 2017 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-29021592

RESUMO

As one of the important gas signal molecules, hydrogen sulfide (H2S) is associated with many important physiological processes in living organisms. Organelles, especially endoplasmic reticulum (ER), play a crucial role in the cell metabolism. Accordingly, the detection of H2S in the ER is of high interest. Toward this goal, we have described the development of the first ER-targeted fluorescent H2S probe (Na-H 2 S-ER). The new probe exhibited favorable features, such as a large turn-on fluorescence signal (45-fold fluorescence enhancement), high sensitivity and selectivity. The probe was successfully employed for imaging exogenous and endogenous H2S in the living HeLa cells. Significantly, the new probe Na-H 2 S-ER was employed to visualize H2S in the ER of living cells for the first time. In addition, the probe was also successfully used for imaging H2S in the living tissues up to a depth of 100 µm and in the living zebrafish.


Assuntos
Retículo Endoplasmático/metabolismo , Corantes Fluorescentes/metabolismo , Sulfeto de Hidrogênio/análise , Imagem Tridimensional , Especificidade de Órgãos , Peixe-Zebra/metabolismo , Animais , Morte Celular , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Fótons , Espectrometria de Fluorescência
13.
Anal Chem ; 89(17): 9388-9393, 2017 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-28795798

RESUMO

Sulfur dioxide (SO2) is a dangerous environmental pollutant. Excessive intake of it may cause some respiratory diseases and even lung cancer. The development of effective methods for detection of SO2 is of great importance for the environment and physiology. Herein, we have designed and synthesized a novel two-photon (TP) and deep-red emission ratiometric fluorescent probe (CP) for detection of SO2. Notably, the novel probe CP exhibited ultrafast response to SO2 in less than 5 s and displayed a great emission shift (195 nm) and a large emission signal ratio variation (enhancement from 0.1347 to 100.14). In addition, the unique probe was successfully employed for imaging SO2 not only in the mitochondria of living cells but also in brain tissues and zebrafishes.


Assuntos
Corantes Fluorescentes/química , Imagem Molecular/métodos , Dióxido de Enxofre/química , Animais , Encéfalo , Células HeLa , Humanos , Ratos , Peixe-Zebra
14.
Acc Chem Res ; 50(6): 1410-1422, 2017 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-28492303

RESUMO

Fluorescence imaging is a rapidly growing technique for noninvasive imaging of biological molecules and processes with high spatial and temporal resolution. For effective biological imaging, it is essential and important to develop robust fluorescent dyes, in particular, near-infrared (NIR) fluorescent dyes with favorable optical properties. Compared with the visible light emitting dyes, NIR dyes have relatively longer emission wavelengths (650-900 nm) with lower energy and are advantageous as imaging agents owing to the minimum photodamage of NIR light to biological samples, deep penetration into tissues, and low interference from autofluorescence of biomolecules. Although great efforts have been devoted to engineer NIR fluorophores, it is still very challenging to regulate their photophysical properties as they often lack optically tunable mechanisms, and this shortcoming considerably restricts the realization of their full potential. Consequently, the rational design of small-molecule optically tunable NIR fluorophores is of high priority and great value. In general, two key characteristics are indispensable for designing excellent optically tunable NIR fluorescent dyes. First, NIR fluorescent dyes should display the maximal absorption and emission located in the NIR region and also have the prominent properties including excellent fluorescence quantum yields, large Stokes shifts, good chemical stability and photostability, low cytotoxicity, and desirable compatibility with biological systems. Second, in principle, functional NIR dyes should also possess optically tunable groups, which can be easily modified to afford responsive sites for the targets of interest. With these considerations in mind, in this Account, we described a unique "integration" strategy for judicious design of the optically tunable NIR fluorophores, which are an intuitive combination of the traditional NIR dyes and the optically tunable mechanisms in the visible light emissive dyes. Thus, the versatile strategy may allow not only retention of the NIR emission properties of NIR dyes but also inheritance of the optically tunable mechanisms from the visible light emissive dyes. By the unique integration strategy, a built-in optically tunable group is strategically installed into the traditional NIR fluorescent dyes to directly tune their optical properties. Herein, we present a concise review of the rational design strategy and biological applications of small-molecule optically tunable NIR fluorescent dyes via the unique integration strategy, and we focused mainly on our work and some representative examples from other groups based on our NIR platforms. This Account includes the detailed integration strategy of each class of the NIR fluorescent dyes, the development of their derivatives, and their imaging applications in living systems.

15.
Methods Mol Biol ; 1594: 129-139, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28456979

RESUMO

Hydrogen peroxide (H2O2) plays important roles in many physiological and pathological processes. At the cellular organelle level, the abnormal concentrations of H2O2 in the lysosomes may cause redox imbalance and the loss of the critical functions of the lysosomes. Herein, we describe the preparation of a potent lysosome-targeted two-photon fluorescent probe (Lyso-HP) for the detection of H2O2 in the lysosomes in the living cells. This unique fluorescent probe can also be employed to effectively detect H2O2 in the living tissues using two-photon fluorescence microscopy.


Assuntos
Peróxido de Hidrogênio/análise , Lisossomos/metabolismo , Microscopia de Fluorescência/métodos , Animais , Corantes Fluorescentes , Células HeLa , Humanos , Peróxido de Hidrogênio/metabolismo , Técnicas In Vitro
16.
Methods Appl Fluoresc ; 5(2): 024005, 2017 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-28430668

RESUMO

As the simplest aldehyde compounds, formaldehyde (FA) is implicated in nervous system diseases and cancer. Endoplasmic reticulum is an organelle that plays important functions in living cells. Accordingly, the development of efficient methods for FA detection in the endoplasmic reticulum (ER) is of great biomedical importance. In this work, we developed the first ER-targeted fluorescent FA probe Na-FA-ER. The detection is based on the condensation reaction of the hydrazine group and FA to suppress the photo-induced electron transfer (PET) pathway, resulting in a fluorescence increase. The novel Na-FA-ER showed high sensitivity to FA. In addition, the Na-FA-ER enabled the bio-imaging of exogenous and endogenous FA in living HeLa cells. Most significantly, the new Na-FA-ER was employed to visualize the endogenous FA in the ER in living cells for the first time.


Assuntos
Retículo Endoplasmático/metabolismo , Corantes Fluorescentes/farmacologia , Formaldeído/metabolismo , Formaldeído/farmacologia , Células HeLa , Humanos , Imagem Óptica
17.
Biosens Bioelectron ; 95: 81-86, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28414951

RESUMO

Thiophenol is a highly toxic compound which is essential in the field of organic synthesis and drug design. However, the accumulation of thiophenols in the environment may cause serious health problems for human bodies ultimately. Therefore, it is critical to develop efficient methods for visualization of thiophenol species in biological samples. In this work, an innovative two-photon fluorescent turn-on probe FR-TP with far-red emission for thiophenols based on FR-NH2 fluorophore and 2,4-dinitrophenylsulfonyl recognition site was reported. The new probe can be used for thiophenol detection with large far-red fluorescence enhancement (about 155-fold), rapid response (completed within 100s), excellent sensitivity (DL 0.363µM), high selectivity, and lower cellular auto-fluorescence interference. Importantly, the probe FR-TP can be successfully employed to visualize thiophenols not only in the living HeLa cells but also in living liver tissues. In addition, through two-photon tissue imaging, the probe was used to monitor and investigate biological thiophenol poisoning in the animal model of thiophenol inhalation for the first time.


Assuntos
Técnicas Biossensoriais , Monitoramento Ambiental , Fenóis/isolamento & purificação , Compostos de Sulfidrila/isolamento & purificação , Corantes Fluorescentes/química , Células HeLa , Humanos , Fenóis/toxicidade , Fótons , Compostos de Sulfidrila/toxicidade
18.
Biosens Bioelectron ; 89(Pt 2): 853-858, 2017 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-27816580

RESUMO

Hypoxia is the important characteristic of solid tumors, and it may cause the bioactivity of nitroreductase (NTR) to display an elevated level. Hence, the development of effective monitoring methods of NTR in living systems is of great importance for detecting the occurrence and progress of tumors. Toward this goal, a novel two-photon fluorescence turn-on NTR probe GCTPOC-HY, based on the two-photon platform GCTPOC and the NTR recognition site p-nitrobenzyl ether, is designed and synthesized. The probe GCTPOC-HY exhibits eminent properties such as high sensitivity and selectivity, highly stable photo-stability, and low cytotoxicity. Besides, the probe responds to 1.5µg/mL NTR with a 130-fold fluorescence enhancement, which is larger than the reported two-photon fluorescent NTR probes. Moreover, the probe GCTPOC-HY is suitable for fluorescence imaging of NTR in living cells by one- and two-photon modes. Importantly, the probe GCTPOC-HY is successfully applied to monitor NTR in the tumor tissues with a significant fluorescence signal and a penetration depth of 70µm by using two-photon microscopy.


Assuntos
Técnicas Biossensoriais/métodos , Neoplasias/diagnóstico , Nitrorredutases/isolamento & purificação , Corantes Fluorescentes/química , Células HeLa , Humanos , Nitrorredutases/genética , Fótons
19.
Chem Commun (Camb) ; 52(75): 11247-11250, 2016 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-27722498

RESUMO

A biotin appended formaldehyde sensor was found to specifically visualise both exogenous and endogenous levels of formaldehyde in biotin receptor positive cells over biotin negative cells by means of one- and two-photon excitation. The probe furthermore visualised endogenous levels of formaldehyde in tumour tissue slices up to 70 µm depth.


Assuntos
Biotina/química , Formaldeído/análise , Neoplasias/patologia , Imagem Óptica , Animais , Linhagem Celular Tumoral , Corantes Fluorescentes/química , Formaldeído/química , Humanos , Imagem Tridimensional , Camundongos , Microscopia Confocal , Células NIH 3T3 , Neoplasias/química , Neoplasias/metabolismo , Fótons , Espectrometria de Fluorescência
20.
Anal Chem ; 88(19): 9359-9363, 2016 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-27653930

RESUMO

As one of the simplest reactive carbonyl species, formaldehyde is implicated in nervous system diseases and cancer. Organelles play crucial roles in various physiological processes in living cells. Accordingly, the detection of endogenous formaldehyde at the subcellular level is of high interest. We herein describe the development of the first organelle-targeted fluorescent formaldehyde probe (Na-FA-Lyso). The new probe exhibits favorable features including a large fluorescence enhancement (about 350-fold) and a fast response to formaldehyde. Significantly, the novel probe Na-FA-Lyso was employed to visualize the endogenous formaldehyde in the lysosomes in living cells for the first time.


Assuntos
Corantes Fluorescentes/farmacologia , Formaldeído/análise , Hidrazinas/farmacologia , Lisossomos/metabolismo , Naftalimidas/farmacologia , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/efeitos da radiação , Corantes Fluorescentes/toxicidade , Células HeLa , Humanos , Hidrazinas/síntese química , Hidrazinas/efeitos da radiação , Hidrazinas/toxicidade , Luz , Naftalimidas/síntese química , Naftalimidas/efeitos da radiação , Naftalimidas/toxicidade
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