TAILIEUCHUNG - Báo cáo khoa học: Angiogenin prevents serum withdrawal-induced apoptosis of P19 embryonal carcinoma cells

Angiogenin is a 14 kDa protein originally identified as an angiogenic pro-tein. Recent development has shown that angiogenin acts on both endothe-lial cells and neuronal cells. Loss-of-function mutations in the coding region of the ANGgene have recently been identified in patients with amyotrophic lateral sclerosis. | ỊFEBS Journal Angiogenin prevents serum withdrawal-induced apoptosis of P19 embryonal carcinoma cells Shuping Li Wenhao Yu Hiroko Kishikawa and Guo-fu Hu Department of Pathology Harvard Medical School Boston MA USA Keywords amyotrophic lateral sclerosis angiogenin apoptosis Bcl-2 Nf-Kb Correspondence . Hu Department of Pathology Harvard Medical School 77 Avenue Louis Pasteur Boston MA 02115 USA Fax 1 617 432 6580 Tel 1 617 432 6582 E-mail guofu_hu@ Received 28 May 2010 revised 1 July 2010 accepted 6 July 2010 doi 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-Kb and Ripkl and downregulates pro-apoptotic genes such as Bakl Tnf Tnfr Trafl and Trp63. Knockdown of Bcl-2 largely abolishes the anti-apoptotic activity of angiogenin whereas the inhibition of Nf-Kb activity results in a partial but significant inhibition of the protective activity of angiogenin. Thus angiog-enin prevents stress-induced cell death through both the Bcl-2 and Nf-Kb pathways. Introduction Angiogenin ANG was originally identified as a tumor angiogenic molecule from the conditioned medium of HT-29 colon adenocarcinoma cells 1 . Its expression is upregulated in a variety of human cancers 2 where it plays a dual role in cancer progression by stimulating both tumor angiogenesis and cancer cell proliferation

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