Poly(ADP-Ribose) Polymerase in the Cellular Response to DNA Damage, Apoptosis, and Disease

Oliver, F. Javier; Murcia, Josiane Ménissier‐de; Murcia, Gilbert de

doi:10.1086/302389

Cited by 137 publications

(113 citation statements)

References 47 publications

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“…4). In addition, cleavage of poly(ADP-ribose) polymerase, an enzyme involved in maintaining DNA integrity and a late-stage marker of apoptosis, 23 was detected by Western analysis of liver homogenates prepared from LPS/GalNtreated Ron TK ϩ/ϩ mice but was barely detectable in homogenates from Ron TK Ϫ/Ϫ mice (data not shown). Taken together, these results show that Ron TK Ϫ/Ϫ mice develop markedly reduced levels of hepatocellular apoptosis in response to LPS/GalN compared with Ron TK ϩ/ϩ mice.…”

Section: Ron Tk ؊/؊ Mice Have a Protected Liver Injurymentioning

confidence: 99%

Deletion of the Ron receptor tyrosine kinase domain in mice provides protection from endotoxin-induced acute liver failure

et al. 2002

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T he Ron receptor tyrosine kinase (TK), also known as stem cell-derived TK, is a heterodimeric single-span transmembrane glycoprotein involved in a wide range of biologic processes, including modulation of inflammatory responses. [1][2][3][4] The intracellular signaling responses of Ron and its only known ligand, the kringle-containing hepatocyte growth factor-like protein, also known as macrophage-stimulating protein, have been studied largely in vitro in resident peritoneal macrophages. To explore the role of the Ron receptor in vivo, our laboratory generated mice with the deletion of the TK domain of the Ron receptor (Ron TK Ϫ/Ϫ mice). 1 Ron TK Ϫ/Ϫ mice have no overt phenotypic abnormalities; however, the responses of Ron TK Ϫ/Ϫ and other Ron receptor mutant mice in several experimental murine models of inflammation, including injection of endotoxin, are markedly exaggerated compared with Ron TK ϩ/ϩ mice. 1,2,5 Very little is known about the biology of the Ron receptor in the liver, either in vitro or in vivo. Ron messenger RNA and protein have been detected in liver tissue, 6,7 and Ron protein has been localized by immunohistochemistry to the hepatocyte and Kupffer cell populations. 8 Given the observations previously noted with Ron TK Ϫ/Ϫ mice, we hypothesized that mice lacking functional Ron receptor would have exaggerated responses in experimental murine models of lipopolysaccharide (LPS)-and Kupffer cell-mediated liver injury.We tested our hypothesis using a well-characterized LPS-induced murine model of acute liver failure (ALF) in galactosamine (GalN)-sensitized mice. 9-11 LPS-induced

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Section: Ron Tk ؊/؊ Mice Have a Protected Liver Injurymentioning

confidence: 99%

Deletion of the Ron receptor tyrosine kinase domain in mice provides protection from endotoxin-induced acute liver failure

et al. 2002

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“…Caspase activation, upon stress-induced cytochrome c release, leads to the cleavage of particular substrates such as the PARP-1 protein. 74,75 The p38 MAPK can also directly activate cytochrome c release and induce apoptosis, independently of caspase activation. 76 We described here an apoptotic pathway that correlates with the activation of p38a MAPKs and of Casp3.…”

Section: P38 On the Stage: New Properties Of P38 Inhibitorsmentioning

confidence: 99%

A p38 inhibitor allows to dissociate differentiation and apoptotic processes triggered upon LIF withdrawal in mouse embryonic stem cells

et al. 2003

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Mouse embryonic stem cells remain pluripotent when maintained in the presence of leukemia inhibitory factor (LIF). Upon LIF withdrawal, most cells differentiate into various lineages, while some die by apoptosis within 3 days. We have analyzed the activation pattern of the mitogenactivated protein kinase (MAPK) families and characterized the expression profile of selected genes modulated during differentiation or apoptosis. We show that p38 MAPKs are activated first, during the apoptotic crisis, while extracellularregulated kinases and c-Jun N-terminal kinases are induced after the apoptotic crisis in differentiated cells. However, by using both p38 kinase inhibitors (PD169316 and SB203580) and a p38a -/-cell line, we demonstrate that p38a activation is rather a consequence than a cause of apoptosis. We thus reveal novel properties of PD169316, which induces cell survival without impairing cell differentiation, and identify PD169316-sensitive targets like the fibroblast growth factor-5, Brachyury and bcl-2 genes. Finally, we demonstrate that overexpression of the PD169316 -regulated bcl-2 gene prevents LIF withdrawal -induced cell death.

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“…This binding seems to be involved in upstream regulation of p53-dependent damage response (Abramova et al, 1997). A number of recent studies suggest that Poly (ADP-ribose) polymerase, which is induced following DNA strand breaks, plays a role in the regulation of accumulation, activation and DNA binding of p53 following genotoxic stress (Oliver et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Structural and functional involvement of p53 in BER in vitro and in vivo

et al. 2001

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p53 is involved in several DNA repair pathways. Some of these require the speci®c transactivation of p53-dependent genes and others involve direct interactions between the p53 protein and DNA repair associated proteins. Previously, we have shown that p53 acts directly in Base Excision Repair (BER) when assayed under in vitro conditions. Our present data indicate that this involvement is independent of the transcriptional activity of the p53 molecule. We found that under both in vitro and in vivo conditions, a p53 transactivation-de®cient molecule, p53-22-23 was more ecient in BER activity than was wild type p53. However, mutations in the core domain or C-terminal alterations strongly reduced p53-mediated BER activity. These results are consistent with the hypothesis that the involvement of p53 in BER activity, a housekeeping DNA repair pathway, is a prompt and immediate one that does not involve the activation of p53 transactivation-dependent mechanisms, but rather concerns with the p53 protein itself. In an endogenous DNA damage status p53 is active in BER pathways as a protein and not as a transcription factor. Oncogene (2001) 20, 581 ± 589.

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Poly(ADP-Ribose) Polymerase in the Cellular Response to DNA Damage, Apoptosis, and Disease

Cited by 137 publications

References 47 publications

Deletion of the Ron receptor tyrosine kinase domain in mice provides protection from endotoxin-induced acute liver failure

Deletion of the Ron receptor tyrosine kinase domain in mice provides protection from endotoxin-induced acute liver failure

A p38 inhibitor allows to dissociate differentiation and apoptotic processes triggered upon LIF withdrawal in mouse embryonic stem cells

Structural and functional involvement of p53 in BER in vitro and in vivo

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