دورية أكاديمية
Doxycycline Alters the Porcine Renal Proteome and Degradome during Hypothermic Machine Perfusion
العنوان: | Doxycycline Alters the Porcine Renal Proteome and Degradome during Hypothermic Machine Perfusion |
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المؤلفون: | Leonie van Leeuwen, Leonie H. Venema, Raphael Heilig, Henri G. D. Leuvenink, Benedikt M. Kessler |
المصدر: | Current Issues in Molecular Biology, Vol 44, Iss 2, Pp 559-577 (2022) |
بيانات النشر: | MDPI AG, 2022. |
سنة النشر: | 2022 |
المجموعة: | LCC:Biology (General) |
مصطلحات موضوعية: | renal transplantation, ischemia/reperfusion injury, machine perfusion, proteomics, degradomics, Biology (General), QH301-705.5 |
الوصف: | Ischemia-reperfusion injury (IRI) is a hallmark for tissue injury in donation after circulatory death (DCD) kidneys. The implementation of hypothermic machine perfusion (HMP) provides a platform for improved preservation of DCD kidneys. Doxycycline administration has shown protective effects during IRI. Therefore, we explored the impact of doxycycline on proteolytic degradation mechanisms and the urinary proteome of perfused kidney grafts. Porcine kidneys underwent 30 min of warm ischemia, 24 h of oxygenated HMP (control/doxycycline) and 240 min of ex vivo reperfusion. A proteomic analysis revealed distinctive clustering profiles between urine samples collected at T15 min and T240 min. High-efficiency undecanal-based N-termini (HUNTER) kidney tissue degradomics revealed significantly more proteolytic activity in the control group at T-10. At T240, significantly more proteolytic activity was observed in the doxycycline group, indicating that doxycycline alters protein degradation during HMP. In conclusion, doxycycline administration during HMP led to significant proteomic and proteolytic differences and protective effects by attenuating urinary NGAL levels. Ultimately, we unraveled metabolic, and complement and coagulation pathways that undergo alterations during machine perfusion and that could be targeted to attenuate IRI induced injury. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1467-3045 1467-3037 41160053 |
Relation: | https://www.mdpi.com/1467-3045/44/2/39; https://doaj.org/toc/1467-3037; https://doaj.org/toc/1467-3045 |
DOI: | 10.3390/cimb44020039 |
URL الوصول: | https://doaj.org/article/8002f44076ef4bbb9afd41160053021f |
رقم الأكسشن: | edsdoj.8002f44076ef4bbb9afd41160053021f |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 14673045 14673037 41160053 |
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DOI: | 10.3390/cimb44020039 |