Angiogenin prevents serum withdrawal-induced apoptosis of P19 embryonal carcinoma cells.
Angiogenin is a 14 kDa protein originally identified as an angiogenic protein. Recent development has shown that angiogenin acts on both endothelial cells and neuronal cells. Loss-of-function mutations in the coding region of the ANG gene have recently been identified in patients with amyotrophic lateral sclerosis. Angiogenin has been shown to control motor neuron survival and protect neurons from apoptosis under various stress conditions. In this article, we characterize the anti-apoptotic activity of angiogenin in pluripotent P19 mouse embryonal carcinoma cells. Angiogenin prevents serum withdrawal-induced apoptosis. Angiogenin upregulates anti-apoptotic genes, including Bag1, Bcl-2, Hells, Nf-kappab and Ripk1, and downregulates pro-apoptotic genes, such as Bak1, Tnf, Tnfr, Traf1 and Trp63. Knockdown of Bcl-2 largely abolishes the anti-apoptotic activity of angiogenin, whereas the inhibition of Nf-kappab activity results in a partial, but significant, inhibition of the protective activity of angiogenin. Thus, angiogenin prevents stress-induced cell death through both the Bcl-2 and Nf-kappab pathways.
Li
Shuping
S
Department of Pathology, Harvard Medical School, Boston, MA, USA.
Yu
Wenhao
W
Kishikawa
Hiroko
H
Hu
Guo-fu
GF
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D018236:Carcinoma, Embryonal / Q000235:genetics / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D016895:Culture Media, Serum-Free / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012259:Ribonuclease, Pancreatic / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016895:Culture Media, Serum-Free; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; C052617:Bcl2 protein, mouse; D045304:Cytochromes c; C046366:angiogenin; D012259:Ribonuclease, Pancreatic; D020169:Caspases