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Orbital shaking drives differential changes in OK proximal tubule cell metabolism and endocytosis
Author(s) -
Ren Qidong,
Gliozzi Megan L.,
Rittenhouse Natalie L.,
Edmunds Lia R.,
Rbaibi Youssef,
Poholek Amanda C.,
Locker Joseph D.,
Jurczak Michael J.,
Baty Catherine J.,
Weisz Ora A.
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.749.6
Subject(s) - microbiology and biotechnology , endocytic cycle , glycolysis , mechanosensitive channels , nephron , reabsorption , endocytosis , biology , glucose uptake , mechanotransduction , chemistry , metabolism , medicine , kidney , endocrinology , biochemistry , cell , ion channel , receptor , insulin
Kidney proximal tubule (PT) cells have high metabolic demands to drive the extraordinary ion and solute transport, water reabsorption, and endocytic uptake that occur in this nephron segment. Increases in renal blood flow alter glomerular filtration rate (GFR) and lead to rapid mechanosensitive adaptations in PT transport, impacting metabolic demand. Although the PT reabsorbs essentially all of the filtered glucose, PT cells rely primarily on oxidative metabolism rather than glycolysis to meet their energy demands. We lack an understanding of how PT metabolism is impacted by changes in O 2 availability via cortical capillaries and mechanosensitive signaling in response to alterations in luminal flow. Previously, we found that opossum kidney (OK) cells recapitulate key features of PT cells in vivo, including enhanced endocytic uptake and ion transport, when exposed to mechanical stimulation by culture on an orbital shaker. We hypothesized that increased oxygenation resulting from orbital shaking also contributes to this more physiologic phenotype. RNA Seq of OK cells maintained under static conditions or exposed to orbital shaking for up to 96h revealed significant time‐ and culture‐dependent changes in gene expression. Transcriptional and metabolomics data were consistent with a decrease in glycolytic flux and with an increased utilization of aerobic metabolic pathways in cells exposed to orbital shaking. Moreover, we found spatial differences in the pattern of mitogenesis and endocytic capacity in our culture system that highlight the complexity of O 2 ‐dependent and mechanosensitive crosstalk to regulate PT cell function. Support or Funding Information Tsinghua MD Scholars Program NIH R01 DK101484 NIH P30 DK079307 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .