Premium
C‐peptide restores mitochondrial complex 1 activity and lowers superoxide levels in high glucose‐treated murine renal microvascular endothelial cells
Author(s) -
Vejandla Himani L.,
Dabkowski Erinne R.,
Hollander John M.,
Brock Robert W.
Publication year - 2010
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.24.1_supplement.571.10
Subject(s) - superoxide , chemistry , depolarization , mitochondrion , reactive oxygen species , medicine , endocrinology , peptide , mitochondrial ros , biochemistry , enzyme
C‐peptide has been shown to protect against renal dysfunction and other diabetic microvascular complications. High glucose‐mediated microvascular damage, in endothelial cells, is based on excess generation of mitochondrial superoxide. The mitochondrial membrane potential (Δψm) and the amplitude of electrochemical proton gradient regulate superoxide production. The main objective of this study was to determine the effect of C‐peptide on overall mitochondrial function as well as the levels of superoxide in renal microvascular endothelial cells exposed to high glucose (HG ‐ 25 mM) for 24 and 48 h. Using JC‐1 to assess Δψm, we observed that C‐peptide (6.6 nM) restored the HG‐induced hyperpolarization at 24 h, and depolarization at 48 h, back to the normal Δψm levels measured with low glucose (5.5 mM). Respiratory control ratio, a measure of electrochemical coupling determined by polarography, was significantly higher in HG cells treated with C‐peptide compared to HG alone (24 h: p<0.0002 and 48 h: p<0.0155). C‐peptide also prevented HG‐mediated superoxide (p<0.05), as measured by mitosox red fluorescence using flow cytometry. In addition, C‐peptide ameliorated HG‐induced reductions in mitochondrial complex 1 activity. Together, these data demonstrate that C‐peptide protects against endothelial mitochondrial dysfunction during hyperglycemia. Funded, in part, by NIH Grant RO1 DK067582.