PUBLICATION

In vivo tracking cystine/glutamate antiporter-mediated cysteine/cystine pool under ferroptosis

Authors
Li, Z., Li, Y., Yang, Y., Gong, Z., Zhu, H., Qian, Y.
ID
ZDB-PUB-200719-3
Date
2020
Source
Analytica chimica acta   1125: 66-75 (Journal)
Registered Authors
Gong, Zhiyuan, Li, Zhen
Keywords
Cysteine/glutamate transporter (system X(C)(−)), Ferroptosis, Fluorescent imaging strategy, Intracellular cysteine/cystine pool, Zebrafish
MeSH Terms
  • Amino Acid Transport Systems/metabolism*
  • Animals
  • Antiporters/metabolism*
  • Benzylidene Compounds/chemical synthesis
  • Benzylidene Compounds/chemistry
  • Cell Line, Tumor
  • Cysteine/analysis*
  • Ferroptosis/physiology*
  • Fluorescent Dyes/chemical synthesis
  • Fluorescent Dyes/chemistry*
  • Humans
  • Microscopy, Fluorescence
  • Nitriles/chemical synthesis
  • Nitriles/chemistry
  • Optical Imaging
  • Zebrafish
PubMed
32674782 Full text @ Anal. Chim. Acta
Abstract
Cysteine/cystine redox couple plays a vital role in maintaining the cellular redox state of living bio-systems. However, the dynamic changes of the intracellular cysteine/cystine pool mediated by cysteine/glutamate transporter (System XC-) in various cellular processes have remained incompletely understood. Here we established a series of strategies around fluorescent probe CP2 for effectively monitoring the intracellular cysteine level in living cells and in vivo zebrafish model, therefore for tracking dynamic changes of system XC--mediated cysteine/cystine pool under ferroptosis. Living cell imaging and in vivo visualization both revealed that intracellular cysteine levels could be significantly reduced upon blocking system XC- activity and inducing ferroptotic cell death. This kind of blocking was potent against cisplatin-resistant A549R cancer cells, which might bring new potential for treating drug-resistant carcinoma through regulating system XC- and processes of ferroptosis. With further improvements in monitoring tools, understanding of system XC--mediated cystine/cysteine pool and ferroptosis could certainly offer crucial information in more physiological or pathological processes.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping