A Fluorescent Probe for Investigating the Role of Biothiols in Signaling Pathways Associated with Cerebral Ischemia-Reperfusion Injury

Yutao Yang, Ming Ma, Lei Shen, Jusung An, Eunji Kim, Hongmei Liu, Ming Jin, Shuxiang Wang, Jinchao Zhang, Jong Seung Kim, Caixia Yin

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Cerebral ischemia-reperfusion injury (CIRI) is intimately associated with the redox regulation of biothiol, a crucial antioxidant marker that precludes the onset of ROS. We designed a novel fluorescent probe, DCI-Ac-Py, showing various physicochemical properties, such as high selectivity, exceptional signal-to-noise ratio, near-infrared (NIR) optical window, and blood–brain barrier (BBB) penetrability, for detecting biothiols in the brain. The picolinate serves as a specific recognition group that is rapidly activated by biothiol and undergoes nucleophilic substitution with the adjacent acrylic ester to yield the desired NIR probe. Additionally, the probe's lipid solubility is improved through the inclusion of halogen atoms, which aids in penetrating the BBB. Using DCI-Ac-Py, we investigated changes of biothiols in vivo in the brains of mice during CIRI. We found that biothiol-mediated NF-kB classical (P65-related) and nonclassical (RelB-related) pathways contribute to abundant ROS production induced by CIRI and that biothiols are involved in redox regulation. These findings provide new insights into the study of CIRI and shed light on the physiological and pathological mechanisms of biothiols in the brain.

Original languageEnglish
Article numbere202310408
JournalAngewandte Chemie - International Edition
Volume62
Issue number40
DOIs
Publication statusPublished - 2023 Oct 2

Bibliographical note

Funding Information:
The work supported by the National Natural Science Foundation of China (22177025, 21807021, 22325703, 22177026, 22074084), Research Groups of Nature Science Foundation of Hebei Province(B2021201038), the Hebei Province Science Foundation (B2020201074), the Central Government Guided Local Science, Technology Development Fund (Hebei Province, 216Z2603G), the Science Fund for Creative the Interdisciplinary Research Program of Natural Science of Hebei University (DXK202113), and the National Research Foundation of Korea (CRI project no. 2018R1A3B1052702, J. S. Kim).

Publisher Copyright:
© 2023 Wiley-VCH GmbH.

Keywords

  • Biothiol
  • Blood-Brain Barrier
  • Cerebral Ischemia-Reperfusion Injury
  • Fluorescent Probes
  • NF-κB Pathway

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry

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