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Hydrodynamic Delivery of Isocitrate Dehydrogenase II for the Treatment of Acute Kidney Injury
Author(s) -
Kolb Alexander,
Atkinson Simon,
Bacallao Robert
Publication year - 2017
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.31.1_supplement.778.5
Subject(s) - isocitrate dehydrogenase , acute kidney injury , kidney , idh2 , renal function , nad+ kinase , medicine , mitochondrion , bioinformatics , biology , chemistry , gene , microbiology and biotechnology , biochemistry , idh1 , enzyme , mutation
Mitochondrial Respiration is a critical process for normal kidney function. Kidneys that undergo an Acute Kidney Injury (AKI), specifically those injuries that result from ischemia, lead to changes in mitochondrial function and respiration. These changes in respiration are due to changes in TCA, Electron Transport Chain complexes, and regulation of ROS levels. To study mitochondrial changes in the kidney as a result of an AKI a proteomic screen was conducted on kidneys two weeks after ischemic injury. The screen indicated that in response to an ischemic event there was an upregulation of proteins that may play a pivotal role in kidney recovery and subsequent protection from future ischemic events. One such protein, Isocitrate Dehydrogenase 2 (IDH2) plays an important role in the TCA and ROS clearance. Treatment of AKI is limited to supportive care, which was reported to cost patients approximately 10 billion dollars in 2012. The limitations and cost of treatment lead to the idea of gene therapy as a possible means of treatment. However, delivering genes directly to the kidney and getting sufficient levels of expression has proven difficult. Recently a novel technique, hydrodynamic delivery, has shown promising results as a possible route of delivery for our genes. This technique uses pressure as a means to deliver genes, dyes, and vectors into the kidney. Our data indicates that hydrodynamic delivery of genes, such as IDH2, block creatinine increase, increase mitochondrial membrane potential, respiration, NAD(P)H and ATP levels compared to control or saline only models. Support or Funding Information NIH/NIDDKVA merit