High dose of lipoxin A4 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, CHAO LU, LING DONG, ZHOU, Guo-Ping, HE, Zha-Guang, CHEN, Zi-Qing
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier 01.08.2005
• Subjects: Animals; Apoptosis; Biological and medical sciences; Calcium - metabolism; Calpain - genetics; Calpain - metabolism; Carrier Proteins - genetics; Carrier Proteins - metabolism; Caspase 3; Caspases - genetics; Caspases - metabolism; Cells, Cultured; Down-Regulation; Fibroblasts - drug effects; Fundamental and applied biological sciences. Psychology; Kidney - cytology; Lipoxins - administration & dosage; Lipoxins - pharmacology; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; Oligodeoxyribonucleotides, Antisense - genetics; Oligodeoxyribonucleotides, Antisense - pharmacology; Phosphorylation; Rats; Up-Regulation; Vertebrates: endocrinology; Vertebrata; Mammalia; Rat; Cell death; Animal; Rodentia; Fibroblast; Apoptosis
• ISSN: 0952-3278; 1532-2823
• DOI: 10.1016/j.plefa.2005.02.005

Studies have implicated that lipoxinA4 (LXA4) inhibited nuclear factor-kappaB (NF-kappaB), Akt/PKB and PI 3-kinase activity and proliferation of glomerular mesangial cells. It is speculated that LXA4 might serve as pro-apoptotic factor. Rat renal interstitial fibroblasts (NRK-49F cells) were exposed to LXA4 in 5% FCS for 24 h. LXA4 at 0.1 and 1 microM induced 9.83% and 33.82% apoptosis of the cells, respectively, upregulated the expression of calpain 10 and Smac, the levels of [Ca2+]i and activity of caspase-3, and downregulated the activity of STAT3 and threonine phosphorylated Akt1. Transfection of calpain 10 or Smac antisense oligodeoxynucleotide into the cells inhibited the LXA4-induced apoptosis, activity of caspase-3. Pretreatment of the cells with calcium inhibitor SK&F96365 inhibited the LXA4-induced apoptosis, levels of [Ca2+]i, expression of calpain 10 and Smac. In conclusion, LXA4 at high concentrations induced apoptosis of renal interstitial fibroblasts via [Ca2+]i-dependent upregulation of calpain 10 and Smac expression.