Oxyhemoglobin produces necrosis, not apoptosis, in astrocytes

Rollins, Shadon; Perkins, Eddie; Mandybur, George; Zhang, Junyi

doi:10.1016/s0006-8993(02)02562-3

Cited by 16 publications

(10 citation statements)

References 36 publications

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“…These data complement the flow cytometry results in showing the range of HDACI-induced susceptibility to apoptosis seen in gliomas. Our observation that primary astrocytes express exceedingly low levels of PARP proform is consistent with previously published reports (39).…”

Section: Effect Of Butyric Acid Prodrugs On Proliferation and Colony supporting

confidence: 93%

Butyric acid prodrugs are histone deacetylase inhibitors that show antineoplastic activity and radiosensitizing capacity in the treatment of malignant gliomas

Entin–Meer

Rephaeli

Yang

et al. 2005

Molecular Cancer Therapeutics

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Histone modification has emerged as a promising approach to cancer therapy. We explored the efficacy of a novel class of histone deacetylase inhibitors in the treatment of malignant gliomas. Treatment of glioma cell lines with two butyric acid derivatives, pivaloylomethyl butyrate (AN-9) and butyroyloxymethyl butyrate (AN-1), induced hyperacetylation, increased p21Cip1 expression, inhibited proliferation, and enhanced apoptosis. Histone deacetylase inhibitor -induced apoptosis was mediated primarily by caspase-8. Treatment of cells with AN-1 or AN-9 for 24 hours before exposure to ;-irradiation potentiated further caspase-8 activity and resultant apoptosis. Clonogenic survival curves revealed marked reductions in cell renewal capacity of U251 MG cells exposed to combinations of AN-1 and radiation. Preliminary in vivo experiments using human glioma cell lines grown as xenografts in mouse flanks suggest in vivo efficacy of AN-9. The data suggest that novel butyric acid prodrugs provide a promising treatment strategy for malignant gliomas as single agents and in combination with radiation therapy.

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Section: Effect Of Butyric Acid Prodrugs On Proliferation and Colony supporting

confidence: 93%

Butyric acid prodrugs are histone deacetylase inhibitors that show antineoplastic activity and radiosensitizing capacity in the treatment of malignant gliomas

Entin–Meer

Rephaeli

Yang

et al. 2005

Molecular Cancer Therapeutics

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“…A study using cultured cells showed a high oxyhemoglobin concentration induced necrosis in aortic smooth muscle cells, suggesting necrosis contributes to vascular wall changes after SAH (Ogihara et al, 2001). Oxyhemoglobin also exerts a necrotic effect on cultured astrocytes (Rollins et al, 2002). Considering the discrepancy between in vitro study and in vivo studies, animal SAH experiments must be performed.…”

Section: 3 Neurobiological Response After Sahmentioning

confidence: 99%

Controversies and evolving new mechanisms in subarachnoid hemorrhage

Chen

Feng

Sherchan

et al. 2014

Progress in Neurobiology

319

264

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Despite decades of study, subarachnoid hemorrhage (SAH) continues to be a serious and significant health problem in the United States and worldwide. The mechanisms contributing to brain injury after SAH remain unclear. Traditionally, most in vivo research has heavily emphasized the basic mechanisms of SAH over the pathophysiological or morphological changes of delayed cerebral vasospasm after SAH. Unfortunately, the results of clinical trials based on this premise have mostly been disappointing, implicating some other pathophysiological factors, independent of vasospasm, as contributors to poor clinical outcomes. Delayed cerebral vasospasm is no longer the only culprit. In this review, we summarize recent data from both experimental and clinical studies of SAH and discuss the vast array of physiological dysfunctions following SAH that ultimately lead to cell death. Based on the progress in neurobiological understanding of SAH, the terms “early brain injury” and “delayed brain injury” are used according to the temporal progression of SAH-induced brain injury. Additionally, a new concept of the vasculo-neuronal-glia triad model for SAH study is highlighted and presents the challenges and opportunities of this model for future SAH applications.

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“…TUNEL staining was performed on paraffin embedded sections using the In Situ Cell Death Detection Kit, Fluorescein (Roche Diagnostics, Mannheim, Germany) as described previously (Ogihara et al 2000;Rollins et al 2002). This kit labels DNA strand breaks that are generated during apoptosis, allowing for the differentiation of apoptosis from necrosis.…”

Section: Tunel and Hsp27 Immunohistochemistry Double Fluoresce Stainingmentioning

confidence: 99%

Mechanisms of Erythropoietin-induced Brain Protection in Neonatal Hypoxia-Ischemia Rat Model

Sun

Zhou

Polk

et al. 2004

J Cereb Blood Flow Metab

105

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Summary: Erythropoietin, a hemotopoietic growth factor, has brain protective actions. This study investigated the mechanisms of Recombinant Human EPO (rhEPO)-induced brain protection in neonates. An established rat hypoxia-ischemia model was used by ligation of the right common carotid artery of 7-day-old pups, followed by 90 minute of hypoxia (8% 0 2 and 92% N 2 ) at 37°C. Animals were divided into three groups: control, hypoxia-ischemia, and hypoxia-ischemia plus rhEPO treatment. In rhEPO treated pups, 300 units rhEPO was administered intraperitoneally 24 hours before hypoxia. rhEPO treatment (300 units) was administered daily for an additional 2 days. ELISA and immunohistochemistry examined the expression of EPO and EPOR. Brain weight, morphology, TUNEL assay, and DNA laddering evaluated brain protection. rhEPO abolished mortality (from 19% to 0%) during hypoxia insult, increased brain weight from 52% to 88%, reduced DNA fragmentation, and decreased TUNEL-positive cells. Real-time RT-PCR, Western blot, and immunohistochemistry revealed an enhanced expression of heat shock protein 27 (HSP27) in ischemic brain hemisphere. Double labeling of TUNEL with HSP27 showed most HSP27 positive cells were negative to TUNEL staining. rhEPO reduces brain injury, especially apoptotic cell death after neonatal hypoxia-ischemia, partially mediated by the activation of HSP27. Key Words: apoptosisbrain injury-heat shock protein-RT-PCR.

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Oxyhemoglobin produces necrosis, not apoptosis, in astrocytes

Cited by 16 publications

References 36 publications

Butyric acid prodrugs are histone deacetylase inhibitors that show antineoplastic activity and radiosensitizing capacity in the treatment of malignant gliomas

Butyric acid prodrugs are histone deacetylase inhibitors that show antineoplastic activity and radiosensitizing capacity in the treatment of malignant gliomas

Controversies and evolving new mechanisms in subarachnoid hemorrhage

Mechanisms of Erythropoietin-induced Brain Protection in Neonatal Hypoxia-Ischemia Rat Model

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