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Proc Natl Acad Sci U S A ; 111(26): 9567-72, 2014 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-24927546

RESUMEN

The Precambrian explosion led to the rapid appearance of most major animal phyla alive today. It has been argued that the complexity of life has steadily increased since that event. Here we challenge this hypothesis through the characterization of apoptosis in reef-building corals, representatives of some of the earliest animals. Bioinformatic analysis reveals that all of the major components of the death receptor pathway are present in coral with high-predicted structural conservation with Homo sapiens. The TNF receptor-ligand superfamilies (TNFRSF/TNFSF) are central mediators of the death receptor pathway, and the predicted proteome of Acropora digitifera contains more putative coral TNFRSF members than any organism described thus far, including humans. This high abundance of TNFRSF members, as well as the predicted structural conservation of other death receptor signaling proteins, led us to wonder what would happen if corals were exposed to a member of the human TNFSF (HuTNFα). HuTNFα was found to bind directly to coral cells, increase caspase activity, cause apoptotic blebbing and cell death, and finally induce coral bleaching. Next, immortalized human T cells (Jurkats) expressing a functional death receptor pathway (WT) and a corresponding Fas-associated death domain protein (FADD) KO cell line were exposed to a coral TNFSF member (AdTNF1) identified and purified here. AdTNF1 treatment resulted in significantly higher cell death (P < 0.0001) in WT Jurkats compared with the corresponding FADD KO, demonstrating that coral AdTNF1 activates the H. sapiens death receptor pathway. Taken together, these data show remarkable conservation of the TNF-induced apoptotic response representing 550 My of functional conservation.


Asunto(s)
Adaptación Biológica/genética , Antozoos/genética , Apoptosis/genética , Evolución Biológica , Receptores del Factor de Necrosis Tumoral/genética , Factor de Necrosis Tumoral alfa/genética , Adaptación Biológica/inmunología , Animales , Antozoos/metabolismo , Apoptosis/efectos de los fármacos , Células Cultivadas , Biología Computacional , Electroforesis en Gel Bidimensional , Proteína de Dominio de Muerte Asociada a Fas/genética , Proteína de Dominio de Muerte Asociada a Fas/metabolismo , Citometría de Flujo , Técnicas de Inactivación de Genes , Humanos , Inmunohistoquímica , Células Jurkat , Microscopía Fluorescente , Receptores de Muerte Celular/metabolismo , Especificidad de la Especie , Factor de Necrosis Tumoral alfa/farmacología
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