Mitochondrial Membrane Potential in Human Neutrophils Is Maintained by Complex III Activity in the Absence of Supercomplex Organisation

Raam, Bram J. van; Sluiter, Wim J.; Wit, E. de; Roos, Dirk; Verhoeven, Arthur J.; Kuijpers, Taco W.

doi:10.1371/journal.pone.0002013

Cited by 138 publications

(157 citation statements)

References 36 publications

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“…Incubation with these agents alone did not induce NET formation and did not affect PMA-induced cell death kinetics (Supplementary information, Figure S3), which suggests that mitochondrial depolarization is not a crucial mediator of DNA decondensation. In this regard, it is noteworthy that neutrophils depend on glycolysis instead of oxidative phosphorylation to meet their energy demands [23,24]. This is in agreement with the profound decrease in the number of mitochondria during differentiation of precursor cells into neutrophils [25].…”

Section: Pma Induces Typical Features Of Netosis Which Differs Both supporting

confidence: 71%

“…To examine whether loss of mitochondrial membrane potential is sufficient to induce NETosis or possibly affects PMA-induced NETosis, we treated neutrophils with the protonophore carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and the complex III inhibitor antimycin A. Both CCCP and antimycin A are known to dissipate the mitochondrial membrane potential in neutrophils [23]. Incubation with these agents alone did not induce NET formation and did not affect PMA-induced cell death kinetics (Supplementary information, Figure S3), which suggests that mitochondrial depolarization is not a crucial mediator of DNA decondensation.…”

Section: Pma Induces Typical Features Of Netosis Which Differs Both mentioning

confidence: 99%

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Neutrophil extracellular trap cell death requires both autophagy and superoxide generation

et al. 2010

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Neutrophil extracellular traps (NETs) are extracellular chromatin structures that can trap and degrade microbes. They arise from neutrophils that have activated a cell death program called NET cell death, or NETosis. Activation of NETosis has been shown to involve NADPH oxidase activity, disintegration of the nuclear envelope and most granule membranes, decondensation of nuclear chromatin and formation of NETs. We report that in phorbol myristate acetate (PMA)-stimulated neutrophils, intracellular chromatin decondensation and NET formation follow autophagy and superoxide production, both of which are required to mediate PMA-induced NETosis and occur independently of each other. Neutrophils from patients with chronic granulomatous disease, which lack NADPH oxidase activity, still exhibit PMA-induced autophagy. Conversely, PMA-induced NADPH oxidase activity is not affected by pharmacological inhibition of autophagy. Interestingly, inhibition of either autophagy or NADPH oxidase prevents intracellular chromatin decondensation, which is essential for NETosis and NET formation, and results in cell death characterized by hallmarks of apoptosis. These results indicate that apoptosis might function as a backup program for NETosis when autophagy or NADPH oxidase activity is prevented.

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Section: Pma Induces Typical Features Of Netosis Which Differs Both supporting

confidence: 71%

Section: Pma Induces Typical Features Of Netosis Which Differs Both mentioning

confidence: 99%

Neutrophil extracellular trap cell death requires both autophagy and superoxide generation

et al. 2010

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“…1B), a proapoptotic protein whose content in neutrophils is very low [28]. Neutrophils contain relatively few mitochondria that maintain their inner mitochondrial membrane potential and play a role in the regulation of apoptosis [29]. Using flow cytometry, we observed that differentiation decreased the stainability of HL-60 cells with a mitochondria-specific dye TMRE (Fig.…”

Section: Differentiation Of Hl-60 Cells By Atra and Dmsomentioning

confidence: 87%

“…Neutrophilic differentiation is associated with changes in the abundance and function of mitochondria. Neutrophils contain few mitochondria which do not produce energy by respiration, but still maintain their ∆Ψ m and regulate the apoptotic processes [29,42]. Neutrophils also have a lowered requirement for cytochrome c for the engagement of the intrinsic pathway [28].…”

Section: Discussionmentioning

confidence: 99%

Neutrophilic differentiation modulates the apoptotic response of HL-60 cells to sodium butyrate and sodium valproate

Vrba¹,

Doležel²,

Ulrichová³

2010

neo

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Histone deacetylases (HDACs) play an important role in regulation of gene expression. Since aberrant upregulation of their activity has been linked to various cancers including leukemic disorders, inhibition of HDACs has emerged as a potential strategy in anticancer therapy. The short chain fatty acids, butyrate and valproate (2-propylvalerate) are effective as HDAC inhibitors at millimolar concentrations [1]. They have been shown to induce, depending on their concentration, monocytic differentiation [2-4] and/or apoptosis in several types of human myeloid leukemic cells [3,[5][6][7]. HDACs have been also identified as molecular targets of all-trans retinoic acid (ATRA) in the treatment of acute promyelocytic leukemia (APL) [8]. Neutrophilic differentiation of normal myeloid cells by ATRA is mediated through the nuclear retinoic acid receptor α (RARα). In the absence of ligand, RARα interacts with nuclear corepressor proteins to form a complex including HDAC1 or HDAC2, resulting in transcriptional repression or silencing. Physiological concentrations of ATRA induce dissociation of the nuclear repressor complex and recruitment of coactivators with histone acetyltransferase activity. This permits the transcriptional activation of differentiation-related genes. In APL cells, the gene encoding RARα appears to be involved in chromosomal translocations, producing several types of RAR-fusion proteins [8,9]. Approximately 98% of APL cases have the t(15;17) translocation leading to the PML-RARα (promyelocytic leukemia protein/RARα) fusion protein. Although ATRA binds to PML-RARα with an affinity comparable to normal RARα, the dissociation of the nuclear repressor complex from PML-RARα and subsequent differentiation occur only at pharmacological doses of ATRA. In contrast, a less common variant of APL with the t(11;17) translocation and the resultant PLZF-RARα (promyelocytic zinc finger protein/RARα) fusion protein has been found resistant to ATRA. This resistance arises from the presence of additional binding site for the nuclear repressor complex in the PLZF moiety of the fusion protein which is insensitive to Received February 3, 2010Differentiation of myeloid leukemic cells may result in less sensitivity to various apoptotic stimuli. We examined whether human leukemia HL-60 cells differentiating by all-trans retinoic acid (ATRA) acquired resistance to the apoptogenic activity of two histone deacetylase (HDAC) inhibitors, butyrate and valproate. In undifferentiated cells, the cytotoxicity of both butyrate and valproate was associated with activation of the intrinsic apoptotic pathway since we observed dissipation of mitochondrial membrane potential, induction of caspase-9 and caspase-3 activities, appearance of sub-G1 DNA and loss of plasma membrane asymmetry and/or integrity. Both HDAC inhibitors were also able to induce accumulation of undifferentiated cells in the G0/G1 phase of the cell cycle. ATRA was found to enhance the apoptotic effect of both butyrate and valproate in undifferentiated cells. This aside, ATRA ...

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“…Cells of myeloid lineages derive their energy almost exclusively from glycolysis, whereas lymphocytes predominantly use oxidative phosphorylation [8,9]. [16].…”

Section: Interconnection Between Rosmentioning

confidence: 99%

Oxidative Stress and Opioids

Vašková¹,

Kočan²,

Vaško³

2016

Glob J Anesth

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In recent years, research has shown the involvement of free radicals in the development of the pain that accompanies many pathological conditions. In the treatment of acute and chronic pain, the most effective therapies are natural and synthetic opioid alkaloids. Their metabolism in itself may contribute to the formation of free radicals and thus affect body system load and the perception of pain. Long-term treatment with opioids is a tool of choice for the treatment of medium and severe pain. Opioids stimulate the effect of endogenous opioids, endorphins, by binding to multiple subtypes of opioid receptors (μ,κ,σ) in spinal, supraspinal and peripheral tissues. Morphine is a typical, natural opioid analgesic utilised in practice in the treatment of severe chronic pain. In addition, similar effects can be expected from semisynthetic opioids such as oxycodone and hydromorphone. However, during treatment with opioids some adverse effects can appear regardless of whether treatment is short-term or long-term. One potentially serious side effect is the induction of oxidative stress. The purpose of this present work is to determine the main sources of reactive oxygen and nitrogen in the development of infl ammatory and neuropathic pain, and the manner in which metabolism of morphine contributes to oxidative stress alone.

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Mitochondrial Membrane Potential in Human Neutrophils Is Maintained by Complex III Activity in the Absence of Supercomplex Organisation

Cited by 138 publications

References 36 publications

Neutrophil extracellular trap cell death requires both autophagy and superoxide generation

Neutrophil extracellular trap cell death requires both autophagy and superoxide generation

Neutrophilic differentiation modulates the apoptotic response of HL-60 cells to sodium butyrate and sodium valproate

Oxidative Stress and Opioids

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