High dose of lipoxin A4 induces apoptosis in rat renal interstitial fibroblasts.
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.
Wu
Sheng-Hua
SH
Department of Pediatrics, Central Laboratory, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, People's Republic of China. littlea9917@sina.com
Lu
Chao
C
Dong
Ling
L
Zhou
Guo-Ping
GP
He
Zha-Guang
ZG
Chen
Zi-Qing
ZQ
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation; D005347:Fibroblasts / Q000187:drug effects*; D007668:Kidney / Q000166:cytology*; D044045:Lipoxins / Q000008:administration & dosage / Q000494:pharmacology*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D015854:Up-Regulation
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C489013:DIABLO protein, rat; D044045:Lipoxins; D024101:Mitochondrial Proteins; D020319:Oligodeoxyribonucleotides, Antisense; C040527:lipoxin A4; D002154:Calpain; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; C415197:calpain 10; D002118:Calcium