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

doi:10.1002/anie.202310408

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

68 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 language	English
Article number	e202310408
Journal	Angewandte Chemie - International Edition
Volume	62
Issue number	40
DOIs	https://doi.org/10.1002/anie.202310408
Publication status	Published - 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.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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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10.1002/anie.202310408

Cite this

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

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.",

keywords = "Biothiol, Blood-Brain Barrier, Cerebral Ischemia-Reperfusion Injury, Fluorescent Probes, NF-κB Pathway",

author = "Yutao Yang and Ming Ma and Lei Shen and Jusung An and Eunji Kim and Hongmei Liu and Ming Jin and Shuxiang Wang and Jinchao Zhang and Kim, \{Jong Seung\} and Caixia Yin",

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: {\textcopyright} 2023 Wiley-VCH GmbH.",

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doi = "10.1002/anie.202310408",

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AU - Ma, Ming

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AU - An, Jusung

AU - Kim, Eunji

AU - Liu, Hongmei

AU - Jin, Ming

AU - Wang, Shuxiang

AU - Zhang, Jinchao

AU - Kim, Jong Seung

AU - Yin, Caixia

N1 - 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.

PY - 2023/10/2

Y1 - 2023/10/2

N2 - 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.

AB - 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.

KW - Biothiol

KW - Blood-Brain Barrier

KW - Cerebral Ischemia-Reperfusion Injury

KW - Fluorescent Probes

KW - NF-κB Pathway

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DO - 10.1002/anie.202310408

M3 - Article

C2 - 37584948

AN - SCOPUS:85169153990

SN - 1433-7851

VL - 62

JO - Angewandte Chemie - International Edition

JF - Angewandte Chemie - International Edition

IS - 40

M1 - e202310408

ER -

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

Abstract

Bibliographical note

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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