Reductive stress imaging in the endoplasmic reticulum by using living cells and zebrafish

Niu, Huanqing; Zhang, Yongru; Zhao, Fangfang; Mo, Saijun; Cao, Wenbo; Ye, Yong; Zhao, Yufen

doi:10.1039/c9cc04711e

Cited by 38 publications

(15 citation statements)

References 37 publications

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“…Many previously reported efforts have focused on the synthesis of dyes for cysteine detection, with at least 24 synthetic dye-based reported to function in detecting cysteine in the past five years (Table 2) [ 257 , 258 , 259 , 260 , 261 , 262 , 263 , 271 , 272 , 273 , 274 , 275 , 276 , 277 , 278 , 279 , 280 , 281 , 282 , 283 , 284 , 285 , 286 , 287 , 288 ]. Of these, several can be targeted to the mitochondria [ 262 , 282 , 285 , 286 ], the Golgi apparatus [ 259 , 276 ], the endoplasmic reticulum [ 274 , 275 ] and the lysosome [ 277 ]. Five act as non-specific sensors, detecting cysteine and other molecules that contain thiol groups or cysteine metabolites, with some using different wavelengths to distinguish between the different ligands [ 258 , 271 , 273 , 280 , 283 ].…”

Section: Fluorescence Imagingmentioning

confidence: 99%

“…Five act as non-specific sensors, detecting cysteine and other molecules that contain thiol groups or cysteine metabolites, with some using different wavelengths to distinguish between the different ligands [ 258 , 271 , 273 , 280 , 283 ]. These synthetic sensors all require irreversible reactions to detect cysteine, negatively affecting kinetics and requiring at least 5 min to an hour for maximum fluorescence [ 257 , 259 , 260 , 262 , 271 , 272 , 273 , 274 , 275 , 276 , 277 , 278 , 279 , 280 , 281 , 282 , 283 , 284 , 285 , 286 , 288 ].…”

Section: Fluorescence Imagingmentioning

confidence: 99%

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The Role of Amino Acids in Neurotransmission and Fluorescent Tools for Their Detection

Dalangin

Kim

Campbell

2020

IJMS

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Neurotransmission between neurons, which can occur over the span of a few milliseconds, relies on the controlled release of small molecule neurotransmitters, many of which are amino acids. Fluorescence imaging provides the necessary speed to follow these events and has emerged as a powerful technique for investigating neurotransmission. In this review, we highlight some of the roles of the 20 canonical amino acids, GABA and β-alanine in neurotransmission. We also discuss available fluorescence-based probes for amino acids that have been shown to be compatible for live cell imaging, namely those based on synthetic dyes, nanostructures (quantum dots and nanotubes), and genetically encoded components. We aim to provide tool developers with information that may guide future engineering efforts and tool users with information regarding existing indicators to facilitate studies of amino acid dynamics.

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Section: Fluorescence Imagingmentioning

confidence: 99%

Section: Fluorescence Imagingmentioning

confidence: 99%

The Role of Amino Acids in Neurotransmission and Fluorescent Tools for Their Detection

Dalangin

Kim

Campbell

2020

IJMS

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“…Deregulation of protein thiol redox may impair protein stability and prolong the ER stress [ 48 ]. Moreover, excessive GSH will cause the ER microenvironment to be in a reduced state, accompanied by reductive stress, which triggers unfolded protein response (UPR) [ 49 ]. We postulate that augmentation of reductive-redox signaling, leading to impaired glutathionylation of oxidized proteins, may cause adverse changes in neuronal function as observed in the current study ( Figs.…”

Section: Discussionmentioning

confidence: 99%

Reductive stress promotes protein aggregation and impairs neurogenesis

et al. 2020

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Redox homeostasis regulates key cellular signaling in both physiology and pathology. While perturbations result in shifting the redox homeostasis towards oxidative stress are well documented, the influence of reductive stress (RS) in neurodegenerative diseases and its mechanisms are unknown. Here, we postulate that a redox shift towards the reductive arm (through the activation of Nrf2 signaling) will damage neurons and impair neurogenesis. In proliferating and differentiating neuroblastoma (Neuro 2a/N2a) cells, sulforaphane-mediated Nrf2 activation resulted in increased transcription/translation of antioxidants and glutathione (GSH) production along with significantly declined ROS in a dose-dependent manner leading to a reductive-redox state ( i.e. RS). Interestingly, this resulted in endoplasmic reticulum (ER) stress leading to subsequent protein aggregation/proteotoxicity in neuroblastoma cells. Under RS, we also observed elevated Tau/α-synuclein and their co-localization with other protein aggregates in these cells. Surprisingly, we noticed that acute RS impaired neurogenesis as evidenced from reduced neurite outgrowth/length. Furthermore, maintaining the cells in a sustained RS condition (for five consecutive generations) dramatically reduced their differentiation and prevented the formation of axons (p < 0.05). This impairment in RS mediated neurogenesis occurs through the alteration of Tau dynamics i.e. RS activates the pathogenic GSK3β/Tau cascade thereby promoting the phosphorylation of Tau leading to proteotoxicity. Of note, intermittent withdrawal of sulforaphane from these cells suppressed the proteotoxic insult and re-activated the differentiation process. Overall, this results suggest that either acute or chronic RS could hamper neurogenesis through GSK3β/TAU signaling and proteotoxicity. Therefore, investigations identifying novel redox mechanisms impacting proteostasis are crucial to preserve neuronal health.

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“…14), for reductive stress imaging. 96 This probe contained a coumarin and pyrazoline derivative as the fluorescent platform. In the presence of Cys, the acrylate group changed to a hydroxyl group, which was involved in an intramolecular hydrogen bond with the nitrogen on the pyrazoline group, producing an intense fluorescence signal.…”

Section: Er-targetable Fluorescent Probesmentioning

confidence: 99%

Recent progress in small-molecule fluorescent probes for endoplasmic reticulum imaging in biological systems

Tang

Zhai

et al. 2022

Analyst

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Reductive stress imaging in the endoplasmic reticulum by using living cells and zebrafish

Abstract: A TP probe, NPCC, was developed for monitoring reductive stress in the ER. It can also distinguish cancer cells from normal cells.

Cited by 38 publications

References 37 publications

The Role of Amino Acids in Neurotransmission and Fluorescent Tools for Their Detection

The Role of Amino Acids in Neurotransmission and Fluorescent Tools for Their Detection

Reductive stress promotes protein aggregation and impairs neurogenesis

Recent progress in small-molecule fluorescent probes for endoplasmic reticulum imaging in biological systems

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