Expression of genes involved in initiation, regulation, and execution of apoptosis in human neutrophils and during neutrophil differentiation of HL-60 cells

Santos-Beneit, Antonio M.; Mollinedo, Faustino

doi:10.1002/jlb.67.5.712

Cited by 106 publications

(96 citation statements)

References 72 publications

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“…However, both inducers cause the G0/G1 cell cycle arrest [13,38] and continuous cell treatment with ATRA or DMSO eventually leads to apoptosis. Both ATRA and DMSO are known to alter the expression of various apoptosis-related genes [12,14,39]. The main role in mediating the apoptosis associated with the terminal differentiation of HL-60 cells is attributed to downregulation of the anti-apoptotic protein Bcl-2 [39,40].…”

Section: Discussionmentioning

confidence: 99%

“…Both ATRA and DMSO are known to alter the expression of various apoptosis-related genes [12,14,39]. The main role in mediating the apoptosis associated with the terminal differentiation of HL-60 cells is attributed to downregulation of the anti-apoptotic protein Bcl-2 [39,40]. Despite the susceptibility to spontaneous apoptosis, differentiation of myeloid leukemic cells along the neutrophilic pathway reduces cell sensitivity to various apoptosis-inducing anticancer drugs with diverse mechanisms of action.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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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“…It is well accepted that the protooncogene Bcl-2 is thought to control mitochondrial permeability transition, allowing the release of cytochrome c. The fact that mature human neutrophils do not express Bcl-2 could also, in addition to the few numbers of mitochondria they report, partly explain the poor ability of these cells to release cytochrome c. In recent years, other interesting Bcl-2-related members have been discovered and their expression at the protein and/or gene level has been detected in various cell types, resulting in the classification of a Bcl-2 protein family. Among these members, some are inhibitors (Bcl-2, Bfl-1, Bcl-x L , Bcl-w, Mcl-1), while others are inducers of apoptosis (Bcl-x S , Bad, Bak, Bax, Bik) (32,33,47,48). In studies of human neutrophils, there are still some ambiguities concerning the expression of some of these Bcl-2 members.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms Involved in Spontaneous and Viscum album Agglutinin-I-Induced Human Neutrophil Apoptosis: Viscum album Agglutinin-I Accelerates the Loss of Antiapoptotic Mcl-1 Expression and the Degradation of Cytoskeletal Paxillin and Vimentin Proteins Via Caspases

Lavastre

Pelletier

Saller

et al. 2002

The Journal of Immunology

137

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Viscum album agglutinin-I (VAA-I) is a plant lectin that possesses interesting potential therapeutic properties and immunomodulatory activities. We have recently found that VAA-I is a potent inducer of human neutrophil apoptosis, but the mechanism(s) involved require further elucidation. In this study, we found that VAA-I alters mitochondrial transmembrane potential and increases intracellular levels of reactive oxygen species (ROS). Despite these observations, treatment with the mitochondrial stabilizer, bongkrekic acid, or with catalase, known to degrade H2O2, fails to reverse VAA-I-induced apoptosis. Moreover, VAA-I was found to induce apoptosis in PLB-985 cells deficient in gp91phox, indicating that the lectin acts via an ROS-independent mechanism. Pretreatment of neutrophils with brefeldin A, an inhibitor of vesicular transport, was found to reverse VAA-I-induced apoptosis. Protein expression of Mcl-1 was decreased by VAA-I. The role of caspases in the degradation of cytoskeletal proteins during both spontaneous and VAA-I-induced neutrophil apoptosis was also investigated. Paxillin and vimentin were markedly degraded by VAA-I when compared with neutrophils that undergo spontaneous apoptosis, but not vinculin or α- and β-tubulin. Caspases were involved in cytoskeletal protein degradation because preincubation with the pan-caspase inhibitor N-benzyloxycarbonyl-V-A-D-O-methylfluoromethyl ketone was found to reverse protein cleavage. We conclude that VAA-I needs to be internalized to mediate apoptosis and that its activity is not dependent on a cell surface receptor-mediated pathway. Also, we conclude that VAA-I induces apoptosis by ROS-independent and Mcl-1-dependent mechanisms and that caspases are involved in cytoskeletal protein degradation in both spontaneous and VAA-I-induced neutrophil apoptosis.

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“…Activation of caspases is one of the earliest markers of apoptosis. Caspase-3 is activated during neutrophil spontaneous apoptosis, and this activation occurs upstream of DNA cleavage in the apoptotic pathway (3,15,30,48). We next determined whether PKC-␦ was acting on TNF-␣-mediated signal transduction at the level of caspase-3 activation.…”

Section: Effect Of Tnf-␣ On Spontaneous Neutrophil Apoptosismentioning

confidence: 99%

A role for PKC-δ and PI 3-kinase in TNF-α-mediated antiapoptotic signaling in the human neutrophil

Kilpatrick

Lee

Haines

et al. 2002

American Journal of Physiology-Cell Physiology

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The proinflammatory cytokine tumor necrosis factor (TNF)-α has been implicated in the attenuation of neutrophil spontaneous apoptosis during sepsis. Antiapoptotic signaling is principally mediated through the p60TNF receptor (p60TNFR). In neutrophils, TNF-α is an incomplete secretagogue and requires input from a ligated integrin(s) for neutrophil activation. In adherent neutrophils, TNF-α triggers association of both protein kinase C (PKC)-δ and phosphatidylinositol (PI) 3-kinase with the p60TNFR. In this study, a role for PKC-δ and PI 3-kinase in TNF-α-mediated antiapoptotic signaling was examined. TNF-α inhibited spontaneous apoptosis in fibronectin-adherent neutrophils, and this antiapoptotic signaling was blocked by the PKC-δ inhibitor rottlerin, but not by an inhibitor of Ca2+-dependent PKC isotypes, Go-6976. Inhibition of PI 3-kinase by LY-294002 also inhibited TNF-α-mediated antiapoptotic signaling. Cycloheximide blocked TNF-α-mediated antiapoptotic signaling, suggesting protein synthesis is required. Inhibition of either PKC-δ or PI 3-kinase attenuated TNF-α-mediated activation of the antiapoptotic transcription factor NFκB. Thus both PKC-δ and PI 3-kinase have essential roles in TNF-α-mediated antiapoptotic signaling in adherent neutrophils.

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Expression of genes involved in initiation, regulation, and execution of apoptosis in human neutrophils and during neutrophil differentiation of HL-60 cells

Cited by 106 publications

References 72 publications

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

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

Mechanisms Involved in Spontaneous and Viscum album Agglutinin-I-Induced Human Neutrophil Apoptosis: Viscum album Agglutinin-I Accelerates the Loss of Antiapoptotic Mcl-1 Expression and the Degradation of Cytoskeletal Paxillin and Vimentin Proteins Via Caspases

A role for PKC-δ and PI 3-kinase in TNF-α-mediated antiapoptotic signaling in the human neutrophil

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