title: Angiogenin inhibits nuclear translocation of apoptosis inducing factor in a Bcl-2-dependent manner.
abstract: Loss-of-function mutations in angiogenin (ANG) gene were discovered in amyotrophic lateral sclerosis (ALS) patients and ANG has been shown to prevent neuronal death both in vitro and in vivo. The neuro-protective activity of ANG was brought about partially by inhibiting stress-induced apoptosis. ANG attenuates both the extrinsic and the intrinsic apoptotic signals by activating Nf-κb-mediated cell survival pathway and Bcl-2-mediated anti-apoptotic pathway. Here we report that ANG inhibits nuclear translocation of apoptosis inducing factor (AIF), an important cell death-executing molecule known to play a dominant role in neurodegenerative diseases. ANG inhibits serum withdrawal-induced apoptosis by attenuating a series of Bcl-2-dependent events including caspase-3 activation, poly ADP-ribose polymerase-1 (PARP-1) cleavage, and AIF nuclear translocation.
authors.affiliation: Molecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts 02111, USA.
authors.forename: Shuping
authors.initials: S
authors.lastname: Li
authors.forename: Wenhao
authors.initials: W
authors.lastname: Yu
authors.forename: Guo-Fu
authors.initials: GF
authors.lastname: Hu
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D002460:Cell Line; D055785:Gene Knockdown Techniques; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D012259:Ribonuclease, Pancreatic / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000378:metabolism; D015843:Serpins / Q000378:metabolism
chemical_list: D051033:Apoptosis Inducing Factor; D008565:Membrane Proteins; D018696:Neuroprotective Agents; C494830:AIFM1 protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D015843:Serpins; C052617:Bcl2 protein, mouse; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C046366:angiogenin; D012259:Ribonuclease, Pancreatic; D012697:Serine Endopeptidases; C106610:Serpinb9 protein, mouse