Renal function in a mouse model of acute kidney injury is improved by myristoylated protein kinase c epsilon inhibitor
Location
Philadelphia, PA
Start Date
11-5-2022 1:00 PM
End Date
11-5-2022 4:00 PM
Description
Introduction: Delayed graft function (DGF) is a post-transplant acute kidney injury that is caused by prolonged ischemia resulting in oxidative stress-mediated damage during reperfusion. Previously, myr-PKCε- reduced infarct size and serum H2O2 when administered upon reperfusion in an ex vivo rat heart ischemia-reperfusion (I/R) model and in vivo hindlimb I/R model, respectively. Myristoylated protein kinase C epsilon peptide inhibitor (N-myr-EAVSLKPT; myr-PKCε-) is known to confer protection by inhibiting superoxide production from uncoupled endothelial nitric oxide synthase and mitochondrial ATP-sensitive K+ channels. We hypothesized myr-PKCε- would attenuate renal injury, characterized by elevated serum creatinine (Cr) and decreased glomerular filtration rate (GFR), compared to a scrambled control peptide (N-myr-LSETKPAV; myr-PKCε-scram).
Methods: Renal pedicles of male C57BL/6J mice (25–30g) were clamped bilaterally for 19 min. Myr-PKCε- or myr-PKCε-scram (1.6 mg/kg; 20 µM blood) were administered into the tail vein 1 min before unclamping. Cr was measured at baseline, 24h, 72h, and 96h post-injury. GFR was determined with fluorescein-isothiocyanate (FITC)-Sinistrin renal clearance. Data were evaluated by unpaired Student’s t-test.
Results: This bilateral 19 min renal ischemia resulted in significant GFR reduction (Fig. 1) and Cr elevation (Fig. 2) throughout the post-ischemic time-course. Myr-PKCε- (n=6) significantly improved both GFR and Cr at 72h and 96h compared to myr-PKCε-scram control (n=4, p<0.05).
Conclusions: Results support the hypothesis that Myr-PKCε- improves kidney function after 19-min warm ischemic injury. Immunolabeling of PKCε, Kim-1, and NGAL biomarkers will be used to further evaluate PKCε localization and the extent of Myr-PKCε- protection against renal tubular damage.
Embargo Period
5-26-2022
Renal function in a mouse model of acute kidney injury is improved by myristoylated protein kinase c epsilon inhibitor
Philadelphia, PA
Introduction: Delayed graft function (DGF) is a post-transplant acute kidney injury that is caused by prolonged ischemia resulting in oxidative stress-mediated damage during reperfusion. Previously, myr-PKCε- reduced infarct size and serum H2O2 when administered upon reperfusion in an ex vivo rat heart ischemia-reperfusion (I/R) model and in vivo hindlimb I/R model, respectively. Myristoylated protein kinase C epsilon peptide inhibitor (N-myr-EAVSLKPT; myr-PKCε-) is known to confer protection by inhibiting superoxide production from uncoupled endothelial nitric oxide synthase and mitochondrial ATP-sensitive K+ channels. We hypothesized myr-PKCε- would attenuate renal injury, characterized by elevated serum creatinine (Cr) and decreased glomerular filtration rate (GFR), compared to a scrambled control peptide (N-myr-LSETKPAV; myr-PKCε-scram).
Methods: Renal pedicles of male C57BL/6J mice (25–30g) were clamped bilaterally for 19 min. Myr-PKCε- or myr-PKCε-scram (1.6 mg/kg; 20 µM blood) were administered into the tail vein 1 min before unclamping. Cr was measured at baseline, 24h, 72h, and 96h post-injury. GFR was determined with fluorescein-isothiocyanate (FITC)-Sinistrin renal clearance. Data were evaluated by unpaired Student’s t-test.
Results: This bilateral 19 min renal ischemia resulted in significant GFR reduction (Fig. 1) and Cr elevation (Fig. 2) throughout the post-ischemic time-course. Myr-PKCε- (n=6) significantly improved both GFR and Cr at 72h and 96h compared to myr-PKCε-scram control (n=4, p<0.05).
Conclusions: Results support the hypothesis that Myr-PKCε- improves kidney function after 19-min warm ischemic injury. Immunolabeling of PKCε, Kim-1, and NGAL biomarkers will be used to further evaluate PKCε localization and the extent of Myr-PKCε- protection against renal tubular damage.