Utilize este identificador para referenciar este registo: http://hdl.handle.net/10451/21212
Título: Noncleavable poly(ADP-ribose) polymerase-1 regulates the inflammatbn response in mice
Autor: Petrilli, V
Herceg, Z
Hassa, PO
Patel, NSA
Di Paola, R
Cortes, U
Dugo, L
Filipe, HM
Thiemermann, C
Hottiger, MO
Cuzzocrea, S
Wang, ZQ
Palavras-chave: Medicine, Research & Experimental
Data: 2004
Citação: JOURNAL OF CLINICAL INVESTIGATION. - Vol. 114, n. 8 (OCT 2004), p. 1072-1081
Resumo: Poly(ADP-ribosyl)ation is rapidly formed in cells following DNA damage and is regulated by poly(ADP-ribose) polymerase-1 (PARP-1). PARP-1 is known to be involved in various cellular processes, such as DNA repair, genomic stability, transcription, and cell death. During apoptosis, PARP-1 is cleaved by caspases to generate 89-kDa and 24-kDa fragments, a hallmark of apoptosis. This cleavage is thought to be a regulatory event for cellular death. In order to understand the biological significance of PARP-1 cleavage, we generated a PARP-1 knockin (PARP-1(KI/KI)) mouse model, in which the caspase cleavage site of PARP-1, DEVD214, was mutated to render the protein resistant to caspases during apoptosis. While PARP-1(KI/KI) mice developed normally, they were highly resistant to endotoxic shock and to intestinal and renal ischemia-reperfusions, which were associated with reduced inflammatory responses in the target tissues and cells due to the compromised production of specific inflammatory mediators. Despite normal binding of NF-kappaB to DNA, NF-kappaB-mediated transcription activity was impaired in the presence of caspase-resistant PARP-1. This study provides a novel insight into the function of PARP-1 in inflammation and ischemia-related pathophysiologies.
URI: http://hdl.handle.net/10451/21212
DOI: http://dx.doi.org/10.1172/JCI200421854
ISSN: 0021-9738
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