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Oxidative stress inhibits Klotho activation of TRPV5 and TRPV6 in intestinal epithelial cells
Author(s) -
Maruggi Marco,
Nguyen Amanda Tu,
Resta Silvia
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.1013.2
Subject(s) - klotho , trpv6 , calcium , oxidative stress , endocrinology , chemistry , calcium metabolism , medicine , western blot , inflammation , oxidative phosphorylation , microbiology and biotechnology , biology , biochemistry , kidney , gene
Calcium is an essential ion in all organisms. We have shown that calcium metabolism is disregulated during chronic inflammation and aging. Klotho is a major player in cell senescence and is associated with calcium metabolism. We hypothesized that oxidative stress in intestinal epithelial cells may cause disregulated calcium balance in the gastrointestinal tract via Klotho disfunction. Caco‐2 and HT29/cl 19A cells were exposed to oxidative stress (H2O2, 100 nM) for 24–72 hr. The cells were then tested for Klotho, TRPV5, TRPV6 mRNA and protein expression, and for calcium transport. H2O2 treatment significantly decreased expression and activity of Klotho vs controls in a time‐dependent manner (1‐, 3‐, 1‐fold decrease at 24, 48, 72 hr, respectively). In parallel, TRPV5 and TRPV6 activity was decreased. Calcium transport was significantly reduced at 24–48 hr, and completely inhibited at 72 hr. H2O2 treatment reversed the co‐immunprecipitation of Klotho and the calcium channels by western blot, and co‐localization by confocal microscopy. We conclude that oxidative stress is in part responsible for the altered calcium metabolism observed in chronic inflammatory diseases through inhibition of Klotho activation of the major intestinal epithelial cell calcium channels. (NIH‐DK062096, SR).