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

• Published in: Prostaglandins, leukotrienes and essential fatty acids Vol. 73; no. 2; pp. 127 - 137
• Main Authors: Wu, Sheng-Hua, Lu, Chao, Dong, Ling, Zhou, Guo-Ping, He, Zha-Guang, Chen, Zi-Qing
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 2005
• ISSN: 0952-3278; 1532-2823
• DOI: 10.1016/j.plefa.2005.02.005

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.