Shrum 2019 Biomolecules

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Shrum S, Rusch NJ, MacMillan-Crow LA (2019) Specific BK channel activator NS11021 protects rat renal proximal tubular cells from cold storage-induced mitochondrial injury in vitro. Biomolecules 9:E825.

» PMID: 31817165 Open Access

Shrum S, Rusch NJ, MacMillan-Crow LA (2019) Biomolecules

Abstract: Kidneys from deceased donors used for transplantation are placed in cold storage (CS) solution during the search for a matched recipient. However, CS causes mitochondrial injury, which may exacerbate renal graft dysfunction. Here, we explored whether adding NS11021, an activator of the mitochondrial big-conductance calcium-activated K+ (mitoBK) channel, to CS solution can mitigate CS-induced mitochondrial injury. We used normal rat kidney proximal tubular epithelial (NRK) cells as an in vitro model of renal cold storage (18 h) and rewarming (2 h) (CS + RW). Western blots detected the pore-forming α subunit of the BK channel in mitochondrial fractions from NRK cells. The fluorescent K+-binding probe, PBFI-AM, revealed that isolated mitochondria from NRK cells exhibited mitoBK-mediated K+ uptake, which was impaired ~70% in NRK cells subjected to CS + RW compared to control NRK cells maintained at 37 °C. Importantly, the addition of 1 M NS11021 to CS solution prevented CS + RW-induced impairment of mitoBK-mediated K+ uptake. The NS11021-treated NRK cells also exhibited less cell death and mitochondrial injury after CS + RW, including mitigated mitochondrial respiratory dysfunction, depolarization, and superoxide production. In summary, these new data show for the first time that mitoBK channels may represent a therapeutic target to prevent renal CS-induced injury.

Keywords: NS11021, Cold storage, Kidney, MitoBK channel, Mitochondria, Oxidative stress, Respiration, Transplantation Bioblast editor: Plangger M O2k-Network Lab: US AR Little Rock MacMillan-Crow LA

Labels: MiParea: Respiration 

Stress:Temperature  Organism: Rat  Tissue;cell: Kidney  Preparation: Permeabilized cells 

Regulation: Ion;substrate transport  Coupling state: LEAK, OXPHOS  Pathway: N, S, CIV, ROX  HRR: Oxygraph-2k 

Labels, 2019-12