Proteomic analysis of Biliverdin protected cerebral ischemia–reperfusion injury in rats

Abstract Biliverdin, a heme metabolite, has been previously reported to alleviate cerebral ischemic reperfusion injury (CIRI). However, the alterations of brain proteome profiles underlying this treatment remain elusive. The objective of this study is to analyze the differential protein expression p...

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Main Authors: Wenya Bai, Siying Huo, Junjie Li, Yuan Yang, Guilin Zhou, Jianlin Shao
Format: Article
Language:English
Published: Nature Portfolio 2023-11-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-47119-3
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author Wenya Bai
Siying Huo
Junjie Li
Yuan Yang
Guilin Zhou
Jianlin Shao
author_facet Wenya Bai
Siying Huo
Junjie Li
Yuan Yang
Guilin Zhou
Jianlin Shao
author_sort Wenya Bai
collection DOAJ
description Abstract Biliverdin, a heme metabolite, has been previously reported to alleviate cerebral ischemic reperfusion injury (CIRI). However, the alterations of brain proteome profiles underlying this treatment remain elusive. The objective of this study is to analyze the differential protein expression profile in cerebral cortex of rats involved in anti-CIRI effects of Biliverdin, providing experimental foundation for searching specific marker proteins. Rat model of MCAO/R was established, HE staining, TTC staining, TUNEL staining, and neurological behavioral examination, corner turning test, adhesive removal test, were performed to validate the effects of Biliverdin, and the results indicated that Biliverdin plays a significant role in alleviating CIRI. Furthermore, proteomic analysis of brain tissues of rats subjected to CIRI following Biliverdin treatment was performed using an integrated TMT-based quantitative proteomic approach coupled with LC-MS/MS technology to clarify the comprehensive mechanisms of Biliverdin in CIRI. First, we conducted strict quality control data for TMT experiments. Finally, a total of 7366 proteins were identified, of which 95 proteins were differentially expressed (DEPs) between the CIRI group and the Sham group and 52 between the CIRI and BV groups. In addition, two overlapping proteins among the 147 DEPs, Atg4c and Camlg, were validated by RT-qPCR and western blotting, and their levels were consistent with the results of TMT analysis. Taken together, the current findings firstly mapped comprehensive proteomic changes after CIRI treated with Biliverdin, providing a foundation for developing potentially therapeutic targets of anti-CIRI of Biliverdin and clinically prognostic biomarkers of stroke.
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spelling doaj.art-287be0d6d69945028d7df942d3c4b1982023-11-26T13:23:18ZengNature PortfolioScientific Reports2045-23222023-11-0113111710.1038/s41598-023-47119-3Proteomic analysis of Biliverdin protected cerebral ischemia–reperfusion injury in ratsWenya Bai0Siying Huo1Junjie Li2Yuan Yang3Guilin Zhou4Jianlin Shao5Department of Anesthesiology, The First Affiliated Hospital of Kunming Medical UniversityDepartment of Anesthesiology, The First Affiliated Hospital of Kunming Medical UniversityDepartment of Anesthesiology, The First Affiliated Hospital of Kunming Medical UniversityDepartment of Anesthesiology, The First Affiliated Hospital of Kunming Medical UniversityDepartment of Anesthesiology, The First Affiliated Hospital of Kunming Medical UniversityDepartment of Anesthesiology, The First Affiliated Hospital of Kunming Medical UniversityAbstract Biliverdin, a heme metabolite, has been previously reported to alleviate cerebral ischemic reperfusion injury (CIRI). However, the alterations of brain proteome profiles underlying this treatment remain elusive. The objective of this study is to analyze the differential protein expression profile in cerebral cortex of rats involved in anti-CIRI effects of Biliverdin, providing experimental foundation for searching specific marker proteins. Rat model of MCAO/R was established, HE staining, TTC staining, TUNEL staining, and neurological behavioral examination, corner turning test, adhesive removal test, were performed to validate the effects of Biliverdin, and the results indicated that Biliverdin plays a significant role in alleviating CIRI. Furthermore, proteomic analysis of brain tissues of rats subjected to CIRI following Biliverdin treatment was performed using an integrated TMT-based quantitative proteomic approach coupled with LC-MS/MS technology to clarify the comprehensive mechanisms of Biliverdin in CIRI. First, we conducted strict quality control data for TMT experiments. Finally, a total of 7366 proteins were identified, of which 95 proteins were differentially expressed (DEPs) between the CIRI group and the Sham group and 52 between the CIRI and BV groups. In addition, two overlapping proteins among the 147 DEPs, Atg4c and Camlg, were validated by RT-qPCR and western blotting, and their levels were consistent with the results of TMT analysis. Taken together, the current findings firstly mapped comprehensive proteomic changes after CIRI treated with Biliverdin, providing a foundation for developing potentially therapeutic targets of anti-CIRI of Biliverdin and clinically prognostic biomarkers of stroke.https://doi.org/10.1038/s41598-023-47119-3
spellingShingle Wenya Bai
Siying Huo
Junjie Li
Yuan Yang
Guilin Zhou
Jianlin Shao
Proteomic analysis of Biliverdin protected cerebral ischemia–reperfusion injury in rats
Scientific Reports
title Proteomic analysis of Biliverdin protected cerebral ischemia–reperfusion injury in rats
title_full Proteomic analysis of Biliverdin protected cerebral ischemia–reperfusion injury in rats
title_fullStr Proteomic analysis of Biliverdin protected cerebral ischemia–reperfusion injury in rats
title_full_unstemmed Proteomic analysis of Biliverdin protected cerebral ischemia–reperfusion injury in rats
title_short Proteomic analysis of Biliverdin protected cerebral ischemia–reperfusion injury in rats
title_sort proteomic analysis of biliverdin protected cerebral ischemia reperfusion injury in rats
url https://doi.org/10.1038/s41598-023-47119-3
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