Evidence for Redox Regulation of Cytochrome c Release during Programmed Neuronal Death: Antioxidant Effects of Protein Synthesis and Caspase Inhibition

Kirkland, Rebecca A.; Franklin, James L.

doi:10.1523/jneurosci.21-06-01949.2001

Cited by 115 publications

(177 citation statements)

References 50 publications

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“…Even though a large body of evidence suggests that ROS can initiate the opening of these pores in many neurodegenerative disease models (Chan, 2005;Kirkland and Franklin, 2001;Kitazawa et al, 2002), little is known of the interplay between CK2 and outer membrane pore formation by Bcl-2 family interaction and requires further elucidation.…”

Section: Discussionmentioning

confidence: 99%

Release of Mitochondrial Apoptogenic Factors and Cell Death are Mediated by CK2 and NADPH Oxidase

Kim

Jung

Narasimhan

et al. 2011

J Cereb Blood Flow Metab

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Activation of the NADPH oxidase subunit, NOX2, and increased oxidative stress are associated with neuronal death after cerebral ischemia and reperfusion. Inhibition of NOX2 by casein kinase 2 (CK2) leads to neuronal survival, but the mechanism is unknown. In this study, we show that in copper/ zinc-superoxide dismutase transgenic (SOD1 Tg) mice, degradation of CK2a and CK2a 0 and dephosphorylation of CK2b against oxidative stress were markedly reduced compared with wildtype (WT) mice that underwent middle cerebral artery occlusion. Inhibition of CK2 pharmacologically or by ischemic reperfusion facilitated accumulation of poly(ADP-ribose) polymers, the translocation of apoptosis-inducing factor (AIF), and cytochrome c release from mitochondria after ischemic injury. The eventual enhancement of CK2 inhibition under ischemic injury strongly increased 8-hydroxy-2 0 -deoxyguanosine and phosphorylation of H2A.X. Furthermore, CK2 inhibition by tetrabromocinnamic acid (TBCA) in SOD1 Tg and gp91 knockout (KO) mice after ischemia reperfusion induced less release of AIF and cytochrome c than in TBCA-treated WT mice. Inhibition of CK2 in gp91 KO mice subjected to ischemia reperfusion did not increase brain infarction compared with TBCA-treated WT mice. These results strongly suggest that NOX2 activation releases reactive oxygen species after CK2 inhibition, triggering release of apoptogenic factors from mitochondria and inducing DNA damage after ischemic brain injury.

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Section: Discussionmentioning

confidence: 99%

Release of Mitochondrial Apoptogenic Factors and Cell Death are Mediated by CK2 and NADPH Oxidase

Kim

Jung

Narasimhan

et al. 2011

J Cereb Blood Flow Metab

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“…4). The other possibility is that bortezomib treatment could alter the oxidation-reduction metabolic pathways and metabolites such as alteration in the intracellular glutathione level, xanthine/xanthine oxidase system, and/or changes in NADPH oxidase in the membrane and the mitochondrial electron transport system (42,43). Moreover, recent reports have shown that ROS production may be associated with the activation of NF B family (44).…”

Section: Discussionmentioning

confidence: 99%

Reactive Oxygen Species Generation and Mitochondrial Dysfunction in the Apoptotic Response to Bortezomib, a Novel Proteasome Inhibitor, in Human H460 Non-small Cell Lung Cancer Cells

Ling

Liebes

Zou

et al. 2003

Journal of Biological Chemistry

431

297

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“…17,19 For example, buthionine sulfoximine (BSO)-induced GSH depletion does not trigger apoptosis, but potentiates death receptor-induced apoptosis in T cells. 17,19 GSH supplementation with N-acetyl-L-cysteine (NAC) also prevents apoptosis [20][21][22] Replenishment of intracellular GSH pools with sulfur amino acids including S-adenosyl-methionine, which is a precursor of GSH through its sequential conversion from S-adenosylhomocysteine (SAH) to cysteine, has also been shown to protect against apoptosis. 18,23 At present, the precise contribution of cytosolic versus mitochondrial GSH pools in apoptosis is not fully understood.…”

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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Evidence for Redox Regulation of Cytochrome c Release during Programmed Neuronal Death: Antioxidant Effects of Protein Synthesis and Caspase Inhibition

Cited by 115 publications

References 50 publications

Release of Mitochondrial Apoptogenic Factors and Cell Death are Mediated by CK2 and NADPH Oxidase

Release of Mitochondrial Apoptogenic Factors and Cell Death are Mediated by CK2 and NADPH Oxidase

Reactive Oxygen Species Generation and Mitochondrial Dysfunction in the Apoptotic Response to Bortezomib, a Novel Proteasome Inhibitor, in Human H460 Non-small Cell Lung Cancer Cells

Apoptosis and glutathione: beyond an antioxidant

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