RESUMO
Monoamine oxidases have two functionally distinct but structurally similar isoforms (MAO-A and MAO-B). The ability to differentiate them by using fluorescence detection/imaging technology is of significant biological relevance, but highly challenging with available chemical tools. Herein, we report the first MAO-A-specific two-photon fluorogenic probe (F1), capable of selective imaging of endogenous MAO-A enzymatic activities from a variety of biological samples, including MAO-A-expressing neuronal SY-SY5Y cells, the brain of tumor-bearing mice and human Glioma tissues by using two-photon fluorescence microscopy (TPFM) with minimal cytotoxicity.
Assuntos
Neoplasias Encefálicas/enzimologia , Corantes Fluorescentes/síntese química , Glioma/enzimologia , Monoaminoxidase/química , Animais , Linhagem Celular , Desenho de Fármacos , Humanos , Camundongos , Microscopia de Fluorescência por Excitação Multifotônica , Neurônios/enzimologiaRESUMO
Monoamine oxidases (MAOs) are the enzymes that catalyze the oxidation of monoamines, such as dopamine, norepinephrine, and serotonin, which serve as key neurotransmitters in the central nervous system (CNS). MAOs play important roles in maintaining the homeostasis of monoamines, and the aberrant expression or activation of MAOs underlies the pathogenesis of monoamine neurotransmitter disorders, including neuropsychiatric and neurodegenerative diseases. Clearly, detecting and inhibiting the activities of MAOs is of great value for the diagnosis and therapeutics of these diseases. Accordingly, many specific detection probes and inhibitors have been developed and substantially contributed to basic and clinical studies of these diseases. In this review, progress in the detecting and inhibiting of MAOs and their applications in mechanism exploration and treatment of neurotransmitter-related disorders is summarized. Notably, how the detection probes and inhibitors of MAOs were developed has been specifically addressed. It is hoped that this review will benefit the design of more effective and sensitive probes and inhibitors for MAOs, and eventually the treatment of monoamine neurotransmitter disorders.
Assuntos
Doenças do Sistema Nervoso Central , Inibidores da Monoaminoxidase/farmacologia , Monoaminoxidase , Animais , Monoaminas Biogênicas/metabolismo , Células Cultivadas , Doenças do Sistema Nervoso Central/tratamento farmacológico , Humanos , Monoaminoxidase/química , Monoaminoxidase/fisiologiaRESUMO
MAO-A promotes the proliferation of human glioma cells. Herein, we report a series of MAO-A specific two-photon small molecular fluorescent probes (A1-5) based on an intramolecular charge transfer enhancing strategy. The activity of endogenous MAO-A can be selectively imaged using A3 as a representative probe in different biological samples including human glioma cells/tissues via two-photon fluorescence microscopy. The study provides new tools for the visual detection of glioma.
Assuntos
Corantes Fluorescentes/química , Glioma/diagnóstico por imagem , Monoaminoxidase/química , Linhagem Celular Tumoral , Transferência Ressonante de Energia de Fluorescência , Humanos , Microscopia de Fluorescência por Excitação Multifotônica , Técnicas de Sonda Molecular , Estrutura Molecular , Monoaminoxidase/genética , Imagem ÓpticaRESUMO
Reactive sulfur species play a very important role in modulating neural signal transmission. Hydrogen polysulfides (H2S n, n > 1) are recently suggested to be the actual signaling molecules. There are still few spatiotemporal controllable-based probes to detect H2S n. In this work, for the first time, we proposed the photocleavage product of the common photoremovable protecting group (2-nitrophenyl moiety) capable of trapping H2S n. Taking advantage of this, we constructed the probe H1 containing a photocontrollable group, a mitochondrial directing unit and a signal reporter fluorescein dye. H1 exhibited excellent fluorescence enhancement (50-fold) in response to H2S n under the aqueous buffer only after UV irradiation. H1 also showed high selectivity and sensitivity for H2S n over other reactive sulfur species, reactive oxygen species, and other analytes, especially biothoils including hydrogen sulfide, cysteine, homocysteine, and glutathione. We showed the utility of H1 to image H2S n in living cells with high spatiotemporal resolution.