Drug metabolite heterogeneity in cultured single cells profiled by pico-trapping direct mass spectrometry

Nanomedicine ◽  
2012 ◽  
Vol 7 (9) ◽  
pp. 1365-1374 ◽  
Author(s):  
Yasufumi Fukano ◽  
Naohiro Tsuyama ◽  
Hajime Mizuno ◽  
Sachiko Date ◽  
Mikihisa Takano ◽  
...  
2020 ◽  
Vol 64 (1) ◽  
pp. 97-110
Author(s):  
Christian Sibbersen ◽  
Mogens Johannsen

Abstract In living systems, nucleophilic amino acid residues are prone to non-enzymatic post-translational modification by electrophiles. α-Dicarbonyl compounds are a special type of electrophiles that can react irreversibly with lysine, arginine, and cysteine residues via complex mechanisms to form post-translational modifications known as advanced glycation end-products (AGEs). Glyoxal, methylglyoxal, and 3-deoxyglucosone are the major endogenous dicarbonyls, with methylglyoxal being the most well-studied. There are several routes that lead to the formation of dicarbonyl compounds, most originating from glucose and glucose metabolism, such as the non-enzymatic decomposition of glycolytic intermediates and fructosyl amines. Although dicarbonyls are removed continuously mainly via the glyoxalase system, several conditions lead to an increase in dicarbonyl concentration and thereby AGE formation. AGEs have been implicated in diabetes and aging-related diseases, and for this reason the elucidation of their structure as well as protein targets is of great interest. Though the dicarbonyls and reactive protein side chains are of relatively simple nature, the structures of the adducts as well as their mechanism of formation are not that trivial. Furthermore, detection of sites of modification can be demanding and current best practices rely on either direct mass spectrometry or various methods of enrichment based on antibodies or click chemistry followed by mass spectrometry. Future research into the structure of these adducts and protein targets of dicarbonyl compounds may improve the understanding of how the mechanisms of diabetes and aging-related physiological damage occur.


2020 ◽  
Author(s):  
Feifei Jia ◽  
Jie Wang ◽  
Yanyan Zhang ◽  
Qun Luo ◽  
Luyu Qi ◽  
...  

<p></p><p><i>In situ</i> visualization of proteins of interest at single cell level is attractive in cell biology, molecular biology and biomedicine, which usually involves photon, electron or X-ray based imaging methods. Herein, we report an optics-free strategy that images a specific protein in single cells by time of flight-secondary ion mass spectrometry (ToF-SIMS) following genetic incorporation of fluorine-containing unnatural amino acids as a chemical tag into the protein via genetic code expansion technique. The method was developed and validated by imaging GFP in E. coli and human HeLa cancer cells, and then utilized to visualize the distribution of chemotaxis protein CheA in E. coli cells and the interaction between high mobility group box 1 protein and cisplatin damaged DNA in HeLa cells. The present work highlights the power of ToF-SIMS imaging combined with genetically encoded chemical tags for <i>in situ </i>visualization of proteins of interest as well as the interactions between proteins and drugs or drug damaged DNA in single cells.</p><p></p>


2016 ◽  
Vol 88 (11) ◽  
pp. 5783-5789 ◽  
Author(s):  
Stijn J. M. Van Malderen ◽  
Eva Vergucht ◽  
Maarten De Rijcke ◽  
Colin Janssen ◽  
Laszlo Vincze ◽  
...  

The Analyst ◽  
2017 ◽  
Vol 142 (10) ◽  
pp. 1703-1710 ◽  
Author(s):  
A. J. Herrmann ◽  
S. Techritz ◽  
N. Jakubowski ◽  
A. Haase ◽  
A. Luch ◽  
...  

High lateral resolution of metal detection in single cells by use of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) demands powerful staining methods.


Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 298
Author(s):  
Raúl González-Domínguez ◽  
Álvaro González-Domínguez ◽  
Ana Sayago ◽  
Juan Diego González-Sanz ◽  
Alfonso María Lechuga-Sancho ◽  
...  

Hydrophilic metabolites are closely involved in multiple primary metabolic pathways and, consequently, play an essential role in the onset and progression of multifactorial human disorders, such as Alzheimer’s disease. This review article provides a comprehensive revision of the literature published on the use of mass spectrometry-based metabolomics platforms for approaching the central metabolome in Alzheimer’s disease research, including direct mass spectrometry, gas chromatography-mass spectrometry, hydrophilic interaction liquid chromatography-mass spectrometry, and capillary electrophoresis-mass spectrometry. Overall, mounting evidence points to profound disturbances that affect a multitude of central metabolic pathways, such as the energy-related metabolism, the urea cycle, the homeostasis of amino acids, fatty acids and nucleotides, neurotransmission, and others.


2018 ◽  
Vol 25 (3) ◽  
pp. 426-433 ◽  
Author(s):  
Leila V. Adamyan ◽  
Natalia Starodubtseva ◽  
Anna Borisova ◽  
Assia A. Stepanian ◽  
Vitaliy Chagovets ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document