Anti-apoptotic peptides protect against radiation-induced cell death

McConnell, Kevin W.; Muenzer, Jared T.; Chang, Kathy; Davis, Christopher G.; McDunn, Jonathan E.; Coopersmith, Craig M.; Hilliard, Carolyn A.; Hotchkiss, Richard S.; Grigsby, Perry W.; Hunt, Clayton R.

doi:10.1016/j.bbrc.2007.01.180

Cited by 21 publications

(16 citation statements)

References 29 publications

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“…Our results suggested that NTHSP could significantly against the morphology changes of spleens and splenocytes apoptosis induced by radiation in mice through the methods of H&E staining and TUNEL staining. This result was in agreement with the result reported by McConnell et al [29].…”

Section: Discussionsupporting

confidence: 94%

Radioprotective activity of neutral polysaccharides isolated from the fruiting bodies of Hohenbuehelia serotina

Wang

2015

Physica Medica

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Section: Discussionsupporting

confidence: 94%

Radioprotective activity of neutral polysaccharides isolated from the fruiting bodies of Hohenbuehelia serotina

Wang

2015

Physica Medica

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“…To directly assess the pathogenic role of NPM-Bax interaction, cells were exposed to a novel synthetic peptide that contained a cell-permeable sequence (41) linked to the 20-amino-acid Bax C-terminal sequence that includes the NPM binding domain (14). Exposure to this NPM-Bax blocking peptide significantly reduced stress-induced cell death (Fig.…”

Section: Resultsmentioning

confidence: 99%

Nucleophosmin, a Critical Bax Cofactor in Ischemia-Induced Cell Death

Wang¹,

Gall

Bonegio

et al. 2013

Molecular and Cellular Biology

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We hypothesized that nucleophosmin (NPM), a nucleolar phosphoprotein, is critical for Bax-mediated cell death. To test this hypothesis, Bax activation was induced by metabolic stress. During stress, nucleolar NPM translocated into the cytosol, NPMBax complexes formed, and both NPM and Bax accumulated in mitochondria. Expression of a cytosol-restricted NPM mutant (NPM-⌬NLS), but not a nucleus-restricted NPM mutant, increased NPM-Bax complex formation, mitochondrial NPM and Bax accumulation, mitochondrial membrane injury, caspase 3 activation, and ischemia-induced cell death. Coexpression of NPM-⌬NLS with constitutively active Bax mutants caused nearly universal cell death in the absence of metabolic stress, whereas expression of active Bax or NPM-⌬NLS alone did not. A Bax peptide that disrupts NPM-Bax interaction significantly reduced cell death caused by exposure to metabolic inhibitors in vitro and preserved kidney function after ischemia in vivo. Thus, NPM-Bax interaction enhances mitochondrial Bax accumulation, organelle injury, and cell death. NPM-Bax complex formation is a novel target for preventing ischemic tissue injury. Although Bax toxicity is well characterized, the events that signal Bax translocation to mitochondria, a major target of Baxmediated apoptosis, are unknown (1). Interestingly, more than 75% of Bax colocalizes with mitochondria during apoptogenic insults, whereas the remaining Bax translocates to nuclei and endoplasmic reticulum or exists unbound in the cytosol (2). Bax lacks a mitochondrial localizing sequence, and a mitochondrial Bax receptor has yet to be identified (3, 4), complicating efforts to dissect the molecular signals that drive intracellular Bax movement and toxicity. The possibility that a molecular chaperone facilitates mitochondrial Bax accumulation has been entertained recently (5, 6).Several Bax chaperones have been proposed (7), including humanin, Ku-70, Bax interacting factor 1 (bif-1), clusterin, specific 14-3-3 isoforms, and nucleophosmin (NPM; also called B23). NPM is an abundant, ubiquitously expressed, 35-kDa phosphoprotein that localizes to the nucleolar region of resting cells (8). In healthy cells, NPM promotes RNA metabolism, as well as the packaging and transport of cell proteins, by reversibly shuttling between the cytosol and the nucleolar region (9, 10). NPM also migrates into the cytosol during cell division to promote ribosomal protein synthesis and cell proliferation before returning to the nucleolar region (5,11,12). These NPM functions are essential, since its elimination causes embryonic death in NPM knockout mice (11).In cell-free systems, NPM interacts with Bax (6, 13). However, NPM only binds Bax that has undergone conformational change characterized by exposure of the amino-terminal 6A7 epitope (6, 14). The site responsible for binding NPM has been identified and localizes to the Bax carboxy-terminal domain (14). Furthermore, a synthetic, 21-amino-acid Bax peptide that includes this carboxyterminal NPM binding site disrupts NPM-Bax interaction in...

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“…Previous studies have shown that BH4 homologues can prevent human or mouse T cells from apoptotic cell death (316–318). However, the degree to which these cells were rescued remains unclear as cell death was not measured extensively.…”

Section: Maintaining T Cell Survival For Therapeutic Purposementioning

confidence: 99%

Dying to protect: cell death and the control of T‐cell homeostasis

Shanmuganad

Carroll

et al. 2017

Immunological Reviews

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Summary T cells play a critical role in immune responses as they specifically recognize peptide/MHC complexes with their T cell receptors (TCRs) and initiate adaptive immune responses. While T cells are critical for performing appropriate effector functions and maintaining immune memory, they also can cause autoimmunity or neoplasia if misdirected or dysregulated. Thus, T cells must be tightly regulated from their development onward. Maintenance of appropriate T cell homeostasis is essential to promote protective immunity and limit autoimmunity and neoplasia. This review will focus on the role of cell death in maintenance of T cell homeostasis and outline novel therapeutic strategies tailored to manipulate cell death to limit T cell survival (eg autoimmunity and transplantation) or enhance T cell survival (eg vaccination, immune-deficiency).

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Anti-apoptotic peptides protect against radiation-induced cell death

Cited by 21 publications

References 29 publications

Radioprotective activity of neutral polysaccharides isolated from the fruiting bodies of Hohenbuehelia serotina

Radioprotective activity of neutral polysaccharides isolated from the fruiting bodies of Hohenbuehelia serotina

Nucleophosmin, a Critical Bax Cofactor in Ischemia-Induced Cell Death

Dying to protect: cell death and the control of T‐cell homeostasis

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