دورية أكاديمية

Doxycycline Alters the Porcine Renal Proteome and Degradome during Hypothermic Machine Perfusion

التفاصيل البيبلوغرافية
العنوان: Doxycycline Alters the Porcine Renal Proteome and Degradome during Hypothermic Machine Perfusion
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
الوصف
تدمد:14673045
14673037
41160053
DOI:10.3390/cimb44020039