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A Fluorescent Probe for Investigating the Role of Biothiols in Signaling Pathways Associated with Cerebral Ischemia-Reperfusion Injury |
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| Authors: | Yutao Yang Ming Ma Lei Shen Jusung An Eunji Kim Hongmei Liu Ming Jin Shuxiang Wang Jinchao Zhang Prof Jong Seung Kim Prof Caixia Yin |
| Institution: | 1. Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Chemical Biology Key Laboratory of Hebei Province, College of Chemistry and Materials Science, Hebei University, Baoding, 071002 P. R. China
Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Molecular Science, Shanxi University, Taiyuan, 030006 China These authors contributed equally to this work.;2. Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Chemical Biology Key Laboratory of Hebei Province, College of Chemistry and Materials Science, Hebei University, Baoding, 071002 P. R. China;3. Department of Chemistry, Korea University, Seoul, 02841 Korea;4. Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Molecular Science, Shanxi University, Taiyuan, 030006 China |
| 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 |