High dose of lipoxin A 4 induces apoptosis in rat renal interstitial fibroblasts

Abstract

Studies have implicated that lipoxinA 4 (LXA 4) inhibited nuclear factor- κB (NF- κB), Akt/PKB and PI 3-kinase activity and proliferation of glomerular mesangial cells. It is speculated that LXA 4 might serve as pro-apoptotic factor. Rat renal interstitial fibroblasts (NRK-49F cells) were exposed to LXA 4 in 5% FCS for 24 h. LXA 4 at 0.1 and 1 μM induced 9.83% and 33.82% apoptosis of the cells, respectively, upregulated the expression of calpain 10 and Smac, the levels of [Ca 2+] i and activity of caspase-3, and downregulated the activity of STAT 3 and threonine phosphorylated Akt 1. Transfection of calpain 10 or Smac antisense oligodeoxynucleotide into the cells inhibited the LXA 4-induced apoptosis, activity of caspase-3. Pretreatment of the cells with calcium inhibitor SK&F96365 inhibited the LXA 4-induced apoptosis, levels of [Ca 2+] i , expression of calpain 10 and Smac. In conclusion, LXA 4 at high concentrations induced apoptosis of renal interstitial fibroblasts via [Ca 2+] i -dependent upregulation of calpain 10 and Smac expression.