Academic Journal
Lessons learned from protein kinase C epsilon peptide mitigation of ischemia/reperfusion injury for post-transplant acute kidney injury (AKI) and the key function of uncoupled endothelial nitric oxide synthase in this process
| العنوان: | Lessons learned from protein kinase C epsilon peptide mitigation of ischemia/reperfusion injury for post-transplant acute kidney injury (AKI) and the key function of uncoupled endothelial nitric oxide synthase in this process |
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| المؤلفون: | Augustin, Taurai, Perkins, Kerry-Anne, Tanoh Boakye, Desmond, Jiang, Yanlin, George, James, Agarwal, Anupam, Young, Lindon H. |
| المصدر: | Research Day |
| سنة النشر: | 2024 |
| المجموعة: | Philadelphia College of Osteopathic Medicine: DigitalCommons@PCOM |
| مصطلحات موضوعية: | Ischemia/Reperfusion Injury, Post-Transplant Acute Kidney Injury (AKI), Endothelial Nitric Oxide Synthase, Medicine and Health Sciences |
| الوصف: | Introduction Ischemia-reperfusion (I/R) injury is marked by increased reactive oxygen species (ROS) during reperfusion, causing cellular injury. Uncoupled endothelial nitric oxide synthase (eNOS) is a major source of ROS in myocardial I/R, hindlimb I/R, and kidney extracorporeal shock wave lithotripsy. During reperfusion, activation of protein kinase C epsilon (PKCε) enhances ROS via uncoupled eNOS due to an increased dihydrobiopterin/tetrahydrobiopterin ratio. Inhibiting uncoupled eNOS using myristic acid conjugated-PKCε peptide inhibitor (N-Myr-EAVSLKPT [Myr-PKCε-]) attenuates ROS. This study examined the effects of Myr-PKCε- in kidney I/R. We hypothesized that Myr-PKCε- will exert renal-protective effects by attenuating PKCε translocation in kidney I/R compared to scrambled control peptide (N-Myr-LSETKPAV [Myr-PKCε-scram]). Methods Renal pedicles of anesthetized male C57BL/6J mice (25–30g) were clamped bilaterally for 19 mins. One minute before unclamping, 1.6 mg/kg Myr-PKCε- (n=6) or Myr-PKCε-scram (n=7) was administered i.v. Glomerular filtration rate (GFR; µl/min) and serum creatinine (Cr; mg/dL) were measured at baseline, 24hrs, 72hrs, and 96hrs post-injury. GFR was determined with localization fluorescein-isothiocyanate (FITC)-Sinistrin renal clearance. Immunohistochemistry (IHC) staining of samples was used to detect the cell membrane of PKCε using AperioImageScope. Data was analyzed using Student’s t-test. Results Myr-PKCε- significantly improved GFR and reduced Cr throughout reperfusion compared to Myr-PKCε-scram (both, p Conclusion Results suggest Myr-PKCε- improved renal function following kidney I/R and mitigated PKCε localization in tubular epithelium compared to Myr-PKCε-scram. Results also suggest that Myr-PKCε decreases PKCε localization in vascular and epithelial renal tissue, leading to less ROS and injury. |
| نوع الوثيقة: | text |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| Relation: | https://digitalcommons.pcom.edu/research_day/research_day_PA_2024/researchPA2024/32; https://digitalcommons.pcom.edu/context/research_day/article/1844/viewcontent/0304_PA_Augustin_Taurai.pdf |
| الاتاحة: | https://digitalcommons.pcom.edu/research_day/research_day_PA_2024/researchPA2024/32 https://digitalcommons.pcom.edu/context/research_day/article/1844/viewcontent/0304_PA_Augustin_Taurai.pdf |
| رقم الانضمام: | edsbas.1A4E7522 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |