Poly (ADP-Ribose) Polymerase Cleavage Monitored In Situ in Apoptotic Cells

O’Brien, Martha A.; Moravec, Richard A.; Riss, Terry

doi:10.2144/01304pf01

Cited by 51 publications

(34 citation statements)

References 31 publications

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“…This was associated with increased cytochrome c translocation in vivo and increased activation of caspase-3 here, as well as in several studies (42,43). The irradiationinduced increase in cytochrome c translocation, together with increased cleavage of the caspase-3 substrate, PARP, and increased TUNEL-labeling in vivo and in vitro are considered to be reliable indicators of apoptosis (44,45). Taken together the data suggest that exposure of rats to ␥-irradiation leads to apoptosis in hippocampus, providing an explanation for the marked cell loss observed in hippocampus following irradiation (46).…”

Section: Figmentioning

confidence: 57%

Analysis of Interleukin-1β-induced Cell Signaling Activation in Rat Hippocampus following Exposure to Gamma Irradiation

Lynch

Moore

Craig

et al. 2003

Journal of Biological Chemistry

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Among the many reported effects of irradiation in cells is activation of the stress-activated protein kinase, c-Jun N-terminal kinase (JNK), which has been shown to result in apoptotic cell death. The trigger that leads to JNK activation has not been identified, although, in rat hippocampus at least, irradiation-induced apoptosis has been coupled with increased accumulation of reactive oxygen species (ROS). Significantly, irradiation-induced changes in hippocampus are abrogated by treatment of rats with the polyunsaturated fatty acid, eicosapentaenoic acid (EPA). A close coupling between ROS accumulation and concentration of the pro-inflammatory cytokine, interleukin-1␤ (IL-1␤) in hippocampus has been reported, and the evidence suggests that IL-1␤ may be responsible for the enhanced ROS production. Here we set out to assess the possibility that whole body ␥-irradiation increases IL-1␤ concentration in hippocampus and to investigate the consequences of such a change. We present evidence that reveals that the irradiation-induced increase in IL-1␤ concentration in hippocampus is accompanied by increased expression of IL-1 type I receptor and IL-1 accessory protein and increased activation of IL-1 receptor-activated kinase. These changes, which were coupled with increased activation of JNK and evidence of apoptotic cell death, were absent in hippocampus of rats that received EPA treatment. Significantly, EPA treatment enhanced hippocampal IL-10 concentration that was inversely correlated with IL-1␤ concentration. The data are consistent with the idea that EPA exerts anti-inflammatory and neuroprotective effects in the central nervous system.

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Section: Figmentioning

confidence: 57%

Analysis of Interleukin-1β-induced Cell Signaling Activation in Rat Hippocampus following Exposure to Gamma Irradiation

Lynch

Moore

Craig

et al. 2003

Journal of Biological Chemistry

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“…We have previously reported that cleavage of PARP was increased in entorhinal cortex of lipopolysaccharide-treated rats, and this change was accompanied by changes in morphology of cells that were indicative of cell death (20). Indeed cleavage of PARP has been considered to be a reliable marked of apoptosis (49,50). Significantly, we observed that these lipopolysaccharide-induced changes were blocked by caspase-1 inhibition pinpointing a role for IL-1␤ in the cascade of events leading to cell death (8).…”

Section: Fig 3 the Age-related Increase In Caspase-3 Activity Is MImentioning

confidence: 58%

Apoptotic Changes in the Aged Brain Are Triggered by Interleukin-1β-induced Activation of p38 and Reversed by Treatment with Eicosapentaenoic Acid

Martin

Lonergan

Boland

et al. 2002

Journal of Biological Chemistry

136

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Among the several changes that occur in the aged brain is an increase in the concentration of the proinflammatory cytokine interleukin-1␤ that is coupled with a deterioration in cell function. This study investigated the possibility that treatment with the polyunsaturated fatty acid eicosapentaenoic acid might prevent interleukin-1␤-induced deterioration in neuronal function. Assessment of four markers of apoptotic cell death, cytochrome c translocation, caspase-3 activation, poly-(ADP-ribose) polymerase cleavage, and terminal dUTP nick-end staining, revealed an age-related increase in each of these measures, and the evidence presented indicates that treatment of aged rats with eicosapentaenoate reversed these changes as well as the accompanying increases in interleukin-1␤ concentration and p38 activation. The data are consistent with the idea that activation of p38 plays a significant role in inducing the changes described since interleukin-1␤-induced activation of cytochrome c translocation and caspase-3 activation in cortical tissue in vitro were reversed by the p38 inhibitor SB203580. The age-related increases in interleukin-1␤ concentration and p38 activation in cortex were mirrored by similar changes in hippocampus. These changes were coupled with an age-related deficit in long term potentiation in perforant path-granule cell synapses, while eicosapentaenoate treatment was associated with reversal of age-related changes in interleukin-1␤ and p38 and with restoration of long term potentiation. Increased expression of the proinflammatory cytokine interleukin-1␤ (IL-1␤)1 has been linked with neurodegenerative disorders like Down's syndrome, Alzheimer's disease, and Parkinson's disease (1, 2). Consistent with the view that IL-1␤ plays a role in deterioration of cell function are the findings that IL-1␤ expression is increased, in parallel with cell damage, in experimental models of ischemia (3), excitotoxicity (4), and traumatic lesions (5). Indeed, IL-1␤ has been shown to trigger cell death in primary cultures of human fetal neurons (6) and inhibition of caspase-1, which leads to formation of active IL-1␤, and blocks lipopolysaccharide-induced changes in cell morphology, which are consistent with cell death (7).IL-1␤ has been shown to stimulate the mitogen-activated protein kinases p38 and c-Jun NH 2 -terminal kinase (8, 9), and activation of both c-Jun NH 2 -terminal kinase (10, 11) and p38 (10, 12-16) has been closely linked with apoptotic cell death. Significantly, an increase in p38 activity has been coupled with apoptotic changes in Alzheimer's disease (17, 18). Concomitant increases in IL-1␤ concentration and p38 activity have been reported in the aged rat brain (19 -21); in hippocampus these changes are correlated with compromised synaptic function and with an age-related impairment in long term potentiation (LTP) (19 -22), while consistent with the high expression of IL-1␤ and IL-1RI in hippocampus is the finding that the cytokine depresses LTP in dentate gyrus (8,19,20,23,24). Significantly, we have ...

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“…When caspases cleave proteins, they generate novel peptide ends that could represent neoepitopes. Generation of antibodies to such neoepitopes has been reported for several caspase protein substrates, including caspases themselves (Srinivasan et al 1998;Knaapen et al 1999;Tanaka et al 2000), and for other substrates, such as PARP (O'Brien et al 2001) and cytokeratin 18 (Caulin et al 1997;Leers et al 1999). The use of such antibodies for immunohistochemistry could represent a specific method for detection of apoptotic cells in archival materials if the substrates are present in many cells and if the neoepitopes are accessible and preserved with routine formaldehyde fixation and paraffin embedding.…”

mentioning

confidence: 99%

Improved Detection of Apoptotic Cells in Archival Paraffin Sections: Immunohistochemistry Using Antibodies to Cleaved Caspase 3

Gown¹,

Willingham

2002

J Histochem Cytochem.

309

224

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Apoptosis has gained central importance in the study of many biological processes, including neoplasia, neurodegenerative diseases, and development. One of the limitations of many studies is the difficulty of specifically identifying individual apoptotic cells. Of the many specific methods developed to detect apoptotic cells, most are not applicable to histological sections of archival paraffin-embedded tissues. Recently, advances in the understanding of the molecular events in apoptosis have led to the realization that caspase activation is by far the most specific indicator of this cell suicide mechanism. Several publications have reported the development of antibodies directed at neoepitopes that are generated in various substrates through the action of caspases. One of these is that present on activated caspase 3, a ubiquitously distributed caspase that is a main effector caspase of the apoptotic cascade within cells. This study demonstrates the utility of using a recently commercially available antibody to cleaved caspase 3 in archival paraffin sections, suggesting that this may be a highly specific and sensitive method generally applicable to many studies of archival material.

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Poly (ADP-Ribose) Polymerase Cleavage Monitored In Situ in Apoptotic Cells

Cited by 51 publications

References 31 publications

Analysis of Interleukin-1β-induced Cell Signaling Activation in Rat Hippocampus following Exposure to Gamma Irradiation

Analysis of Interleukin-1β-induced Cell Signaling Activation in Rat Hippocampus following Exposure to Gamma Irradiation

Apoptotic Changes in the Aged Brain Are Triggered by Interleukin-1β-induced Activation of p38 and Reversed by Treatment with Eicosapentaenoic Acid

Improved Detection of Apoptotic Cells in Archival Paraffin Sections: Immunohistochemistry Using Antibodies to Cleaved Caspase 3

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