Premium
A Novel Mechanism for Acute Hyperglycemia Induced Apoptosis In Renal Epithelial Cells
Author(s) -
Wisdom Erika,
Thekkumkara Thomas
Publication year - 2009
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.23.1_supplement.526.22
Subject(s) - apoptosis , dna fragmentation , fragmentation (computing) , chromatin , chemistry , dna synthesis , microbiology and biotechnology , cell growth , dual role , cell cycle , cell , endocrinology , medicine , dna , programmed cell death , biology , biochemistry , ecology , combinatorial chemistry
Previously, we reported that acute (10‐20 min) exposure of proximal tubule epithelial cells to 25 mM high glucose (HG) induces a time‐dependent dual effect, involving an early (12h) proliferation and a late (48h) apoptosis. In this study, conditioned medium from cells treated with HG (acute) significantly inhibited high glucose‐induced [ 3 H]thymidine incorporation into DNA in fresh cells at 12h. Treatment with conditioned medium increased p53 expression that was inhibited by ROS inhibitor NAC. Under similar conditions, we observed increased chromatin condensation and DNA fragmentation. However, in HG (acute) treated cells replenishment with fresh normal glucose medium at 6h induced only cell proliferation further, confirming the role of secretory factor(s). Consistent with these results, we observed decreased ROS production, DNA fragmentation, and chromatin condensation. Although additional studies are needed to identify HG mediated inhibitory factor(s), our study demonstrates for the first time that a single HG exposure for 20 min alone is sufficient to induce cellular factor(s) capable of eliciting ROS mediated cellular apoptosis leading to epithelial cell dysfunction. Supported by NIH Grant DK072140