Increased infarct size and exacerbated apoptosis in the glutathione peroxidase‐1 (Gpx‐1) knockout mouse brain in response to ischemia/reperfusion injury

Crack, Peter J; Jm, Taylor; Flentjar, Nicole J; Hertzog, Paul J.; Iannello, Rocco C.; Kola, Ismail

doi:10.1046/j.1471-4159.2001.00535.x

Cited by 192 publications

(169 citation statements)

References 35 publications

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“…GPX is an important component in the enzymatic defense system against the increase of free radicals (Crack et al 2001). In this study, the activity of glutathione peroxidase was reduced in lead treated groups (1.25 and 1.08 μg of GSH consumed/min/ mg protein, respectively for 1 week and 3 weeks lead treated groups) when compared to control group (1.34 μg of GSH consumed/min/mg protein).…”

Section: Methodsmentioning

confidence: 59%

Ameliorating activity of ginger (Zingiber officinale) extract against lead induced renal toxicity in male rats

et al. 2011

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Lead poisoning has been known to be associated with structural and functional abnormalities of multiple organ systems of human body. The aim of this investigation was to study the renal protective effects of ginger (Zingiber officinale) extract in lead induced toxicity rats. In this study renal glutathione (GSH) level, glutathione peroxidase (GPX), glutathione-s-transferase (GST), and catalase enzymes were measured in lead nitrate (300 mg/kg BW), and lead nitrate plus ginger extract (150 mg/kg BW) treated rat groups for 1 week and 3 weeks respectively. The glutathione level and GSH dependent antioxidant enzymes such as glutathione peroxidase, glutathione-stransferase, and catalase significantly (P<0.05) increased in ginger extract treated rat groups. In addition, histological studies showed lesser renal changes in lead plus ginger extract treated rat groups than that of lead alone treated rat groups. These results indicate that ginger extract alleviated lead toxic effects by enhancing the levels of glutathione, glutathione peroxidase, glutathiones-transferase and catalase.

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Section: Methodsmentioning

confidence: 59%

Ameliorating activity of ginger (Zingiber officinale) extract against lead induced renal toxicity in male rats

et al. 2011

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“…The mechanism of the GPx1 protective role during brain I/R injury was recently a focus of a report by Crack et al (47). These authors demonstrated that GPx1 knockout mice display increased infarct size and exacerbated apoptosis compared with normal animals after MCA occlusion and reperfusion.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Response and Glutathione Peroxidase in a Model of Stroke

Ishibashi

Prokopenko

Reuhl

et al. 2002

The Journal of Immunology

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Stroke is one of the leading causes of death in major industrial countries. Many factors contribute to the cellular damage resulting from ischemia/reperfusion (I/R). Experimental data indicate an important role for oxidative stress and the inflammatory cascade during I/R. We are testing the hypothesis that the mechanism of protection against I/R damage observed in transgenic mice overexpressing human antioxidant enzymes (particularly intracellular glutathione peroxidase) involves the modulation of inflammatory response as well as reduced sensitivity of neurons to cytotoxic cytokines. Transgenic animals show significant reduction of expression of chemokines, IL-6, and cell death-inducing ligands as well as corresponding receptors in a focal cerebral I/R model. Reduction of DNA binding activity of consensus and potential AP-1 binding sites in mouse Fas ligand promoter sequence was observed in nuclear extracts from transgenic mice overexpressing intracellular glutathione peroxidase compared with normal animals following I/R. This effect was accompanied by modulation of the c-Jun N-terminal kinase/stress-activated protein kinase pathway. Cultured primary neurons from the transgenic mice demonstrated protection against hypoxia/reoxygenation injury as well as cytotoxicity after TNF-α and Fas ligand treatment. These results indicate that glutathione peroxidase-sensitive reactive oxygen species play an important role in regulation of cell death during cerebral I/R by modulating intrinsic neuronal sensitivity as well as brain inflammatory reactions.

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“…GPX1 whose preferred substrate is hydrogen peroxide is the most abundant isoform found in the cytoplasm of nearly all mammalian tissues whereas GPX2 is an intestinal and extracellular enzyme. 82 GPX1 and GPX2 have been reported to protect against apoptosis induced by oxidative stress 83,84 ischemia/reperfusion injury 85 and doxorubicin 86 and to reduce pro-apoptotic Bax expression. 87 GPX4 (also known as phospholipid hydroperoxide glutathione peroxidase, PHGPX) overexpression has been reported to protect against oxidative stress-induced apoptosis.…”

Section: Figure 1 Apoptotic Signaling Pathways (See Text For Further mentioning

confidence: 99%

Apoptosis and glutathione: beyond an antioxidant

2009

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Apoptosis is a conserved homeostatic process critical for organ and tissue morphogenesis, development, and senescence. This form of programmed cell death also participates in the etiology of several human diseases including cancer, neurodegenerative, and autoimmune disorders. Although the signaling pathways leading to the progression of apoptosis have been extensively characterized, recent studies highlight the regulatory role of changes in the intracellular milieu (permissive apoptotic environment) in the efficient activation of the cell death machinery. In particular, glutathione (GSH) depletion is a common feature of apoptotic cell death triggered by a wide variety of stimuli including activation of death receptors, stress, environmental agents, and cytotoxic drugs. Although initial studies suggested that GSH depletion was only a byproduct of oxidative stress generated during cell death, recent discoveries suggest that GSH depletion and post-translational modifications of proteins through glutathionylation are critical regulators of apoptosis. Here, we reformulate these emerging paradigms into our current understanding of cell death mechanisms. Apoptosis or programmed cell death is a ubiquitous homeostatic process involved in numerous biological systems. Under physiological conditions it is critical not only in the turnover of cells in tissues but also during normal development and senescence. Moreover, its deregulation has been widely observed to occur as either a cause or consequence of distinct pathologies including cancer, autoimmune, and neurodegenerative diseases. Apoptosis is a highly organized program induced by a myriad of stimuli that are characterized by the progressive activation of precise pathways leading to specific biochemical and morphological alterations in individual cells without involving an inflammatory response. Early stages of apoptosis are characterized by initiator caspase activation, cell shrinkage, loss of plasma membrane lipid asymmetry, and chromatin condensation. The execution phase of apoptosis is characterized by activation of executioner caspases and endonucleases, apoptotic body formation, and cell fragmentation 1 (Figure 1). Interestingly, recent studies have shown that changes in the intracellular milieu of the cells, such as alterations in the redox environment, are important regulators of the progression to apoptosis. 2 These discoveries have lead to the concept of a permissive apoptotic environment necessary for the activation of the proper signaling pathways regulating apoptosis. Glutathione (GSH) depletion is an early hallmark in the progression of cell death in response to a variety of apoptotic stimuli in numerous cell types 3,4 (Figure 2), although the exact role of GSH depletion in apoptosis is still controversial. We review recent data that show new insights into the understanding of the causes and consequences that alterations in the redox environment of the cell have on apoptosis.The Role of GSH in the Regulation of Apoptosis GSH synthesis, depletion, and apopt...

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Increased infarct size and exacerbated apoptosis in the glutathione peroxidase‐1 (Gpx‐1) knockout mouse brain in response to ischemia/reperfusion injury

Cited by 192 publications

References 35 publications

Ameliorating activity of ginger (Zingiber officinale) extract against lead induced renal toxicity in male rats

Ameliorating activity of ginger (Zingiber officinale) extract against lead induced renal toxicity in male rats

Inflammatory Response and Glutathione Peroxidase in a Model of Stroke

Apoptosis and glutathione: beyond an antioxidant

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