QHRD106 ameliorates ischemic stroke injury as a long-acting tissue kallikrein preparation
Summary: Ischemic stroke is the second leading cause of death worldwide, and there are limited effective treatment strategies. QHRD106, a polyethyleneglycol (PEG)-modified long-acting tissue kallikrein preparation, has not been reported previously. In this study, we aimed to investigate the therapeu...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-07-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223013457 |
| _version_ | 1797774517666316288 |
|---|---|
| author | Si-Yi Xu Jun-Qiu Jia Min Sun Xin-Yu Bao Sheng-Nan Xia Shu Shu Pin-yi Liu Sen-lin Ji Lei Ye Xiang Cao Yun Xu |
| author_facet | Si-Yi Xu Jun-Qiu Jia Min Sun Xin-Yu Bao Sheng-Nan Xia Shu Shu Pin-yi Liu Sen-lin Ji Lei Ye Xiang Cao Yun Xu |
| author_sort | Si-Yi Xu |
| collection | DOAJ |
| description | Summary: Ischemic stroke is the second leading cause of death worldwide, and there are limited effective treatment strategies. QHRD106, a polyethyleneglycol (PEG)-modified long-acting tissue kallikrein preparation, has not been reported previously. In this study, we aimed to investigate the therapeutic effect of QHRD106 in ischemic stroke and its possible mechanism. We found that QHRD106 treatment alleviated brain injury after stroke via bradykinin (BK) receptor B2 (B2R) instead of BK receptor B1 (B1R). Mechanistically, QHRD106 reduced high-mobility group box 1 (HMGB1)-induced apoptosis and inflammation after ischemic stroke in vivo and in vitro. Moreover, we confirmed that QHRD106 reduced the level of acetylated HMGB1 and reduced the binding between heat shock protein 90 alpha family class A member 1 (HSP90AA1) and HMGB1, thus inhibiting the translocation and release of HMGB1. In summary, these findings indicate that QHRD106 treatment has therapeutic potential for cerebral ischemic stroke. |
| first_indexed | 2024-03-12T22:22:16Z |
| format | Article |
| id | doaj.art-f00a754a75e446ddbf39649150c823c3 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-12T22:22:16Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-f00a754a75e446ddbf39649150c823c32023-07-23T04:56:06ZengElsevieriScience2589-00422023-07-01267107268QHRD106 ameliorates ischemic stroke injury as a long-acting tissue kallikrein preparationSi-Yi Xu0Jun-Qiu Jia1Min Sun2Xin-Yu Bao3Sheng-Nan Xia4Shu Shu5Pin-yi Liu6Sen-lin Ji7Lei Ye8Xiang Cao9Yun Xu10Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, Jiangsu 210008, P.R. China; Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, Jiangsu 210008, P.R. ChinaDepartment of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, Jiangsu 210008, P.R. ChinaDepartment of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, Jiangsu 210008, P.R. ChinaDepartment of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, Jiangsu 210008, P.R. China; Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China; Jiangsu Provincial Key Discipline of Neurology, Nanjing, Jiangsu 210008, P.R. China; Nanjing Neurology Medical Center, Nanjing, Jiangsu 210008, P.R. ChinaDepartment of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, Jiangsu 210008, P.R. China; Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China; Jiangsu Provincial Key Discipline of Neurology, Nanjing, Jiangsu 210008, P.R. China; Nanjing Neurology Medical Center, Nanjing, Jiangsu 210008, P.R. ChinaDepartment of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, Jiangsu 210008, P.R. China; Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China; Jiangsu Provincial Key Discipline of Neurology, Nanjing, Jiangsu 210008, P.R. China; Nanjing Neurology Medical Center, Nanjing, Jiangsu 210008, P.R. ChinaDepartment of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, Jiangsu 210008, P.R. China; Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China; Jiangsu Provincial Key Discipline of Neurology, Nanjing, Jiangsu 210008, P.R. China; Nanjing Neurology Medical Center, Nanjing, Jiangsu 210008, P.R. ChinaDepartment of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, Jiangsu 210008, P.R. China; Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China; Jiangsu Provincial Key Discipline of Neurology, Nanjing, Jiangsu 210008, P.R. China; Nanjing Neurology Medical Center, Nanjing, Jiangsu 210008, P.R. ChinaDepartment of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, Jiangsu 210008, P.R. ChinaDepartment of Neurology, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, Jiangsu 210008, P.R. China; Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, Jiangsu 210008, P.R. China; Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China; Jiangsu Provincial Key Discipline of Neurology, Nanjing, Jiangsu 210008, P.R. China; Nanjing Neurology Medical Center, Nanjing, Jiangsu 210008, P.R. China; Corresponding authorDepartment of Neurology, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, Jiangsu 210008, P.R. China; Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, Jiangsu 210008, P.R. China; Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China; Jiangsu Provincial Key Discipline of Neurology, Nanjing, Jiangsu 210008, P.R. China; Nanjing Neurology Medical Center, Nanjing, Jiangsu 210008, P.R. China; Corresponding authorSummary: Ischemic stroke is the second leading cause of death worldwide, and there are limited effective treatment strategies. QHRD106, a polyethyleneglycol (PEG)-modified long-acting tissue kallikrein preparation, has not been reported previously. In this study, we aimed to investigate the therapeutic effect of QHRD106 in ischemic stroke and its possible mechanism. We found that QHRD106 treatment alleviated brain injury after stroke via bradykinin (BK) receptor B2 (B2R) instead of BK receptor B1 (B1R). Mechanistically, QHRD106 reduced high-mobility group box 1 (HMGB1)-induced apoptosis and inflammation after ischemic stroke in vivo and in vitro. Moreover, we confirmed that QHRD106 reduced the level of acetylated HMGB1 and reduced the binding between heat shock protein 90 alpha family class A member 1 (HSP90AA1) and HMGB1, thus inhibiting the translocation and release of HMGB1. In summary, these findings indicate that QHRD106 treatment has therapeutic potential for cerebral ischemic stroke.http://www.sciencedirect.com/science/article/pii/S2589004223013457PharmacologyBiochemistryPhysiologyNeuroscience |
| spellingShingle | Si-Yi Xu Jun-Qiu Jia Min Sun Xin-Yu Bao Sheng-Nan Xia Shu Shu Pin-yi Liu Sen-lin Ji Lei Ye Xiang Cao Yun Xu QHRD106 ameliorates ischemic stroke injury as a long-acting tissue kallikrein preparation iScience Pharmacology Biochemistry Physiology Neuroscience |
| title | QHRD106 ameliorates ischemic stroke injury as a long-acting tissue kallikrein preparation |
| title_full | QHRD106 ameliorates ischemic stroke injury as a long-acting tissue kallikrein preparation |
| title_fullStr | QHRD106 ameliorates ischemic stroke injury as a long-acting tissue kallikrein preparation |
| title_full_unstemmed | QHRD106 ameliorates ischemic stroke injury as a long-acting tissue kallikrein preparation |
| title_short | QHRD106 ameliorates ischemic stroke injury as a long-acting tissue kallikrein preparation |
| title_sort | qhrd106 ameliorates ischemic stroke injury as a long acting tissue kallikrein preparation |
| topic | Pharmacology Biochemistry Physiology Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223013457 |
| work_keys_str_mv | AT siyixu qhrd106amelioratesischemicstrokeinjuryasalongactingtissuekallikreinpreparation AT junqiujia qhrd106amelioratesischemicstrokeinjuryasalongactingtissuekallikreinpreparation AT minsun qhrd106amelioratesischemicstrokeinjuryasalongactingtissuekallikreinpreparation AT xinyubao qhrd106amelioratesischemicstrokeinjuryasalongactingtissuekallikreinpreparation AT shengnanxia qhrd106amelioratesischemicstrokeinjuryasalongactingtissuekallikreinpreparation AT shushu qhrd106amelioratesischemicstrokeinjuryasalongactingtissuekallikreinpreparation AT pinyiliu qhrd106amelioratesischemicstrokeinjuryasalongactingtissuekallikreinpreparation AT senlinji qhrd106amelioratesischemicstrokeinjuryasalongactingtissuekallikreinpreparation AT leiye qhrd106amelioratesischemicstrokeinjuryasalongactingtissuekallikreinpreparation AT xiangcao qhrd106amelioratesischemicstrokeinjuryasalongactingtissuekallikreinpreparation AT yunxu qhrd106amelioratesischemicstrokeinjuryasalongactingtissuekallikreinpreparation |