Chemotherapeutic Drugs Induce ATP Release via Caspase-gated Pannexin-1 Channels and a Caspase/Pannexin-1-independent Mechanism

Boyd-Tressler, Andrea; Peñuela, Silvia; Laird, Dale W.; Dubyak, George R.

doi:10.1074/jbc.m114.590240

Cited by 72 publications

(67 citation statements)

References 83 publications

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“…However, nonvesicular mechanisms that contribute to the cellular release of ATP in many cell types also could be involved in the release of UDP-sugars. For example, caspase 3-mediated proteolytic irreversible activation of plasma membrane pannexin 1 channels resulted in robust release of cytosolic ATP, as well as ADP, AMP, and UTP, from apoptotic lymphocytes (Elliott et al, 2009;Chekeni et al, 2010;Boyd-Tressler et al, 2014). These data suggest that the pannexin 1 pore exhibits no specificity toward nucleotide species.…”

Section: Mechanisms Of Release and Metabolism Of Nucleotide Sugarsmentioning

confidence: 74%

UDP-Sugars as Extracellular Signaling Molecules: Cellular and Physiologic Consequences of P2Y₁₄ Receptor Activation

Lazarowski

Harden

2015

Mol Pharmacol

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UDP-sugars, which are indispensable for protein glycosylation reactions in cellular secretory pathways, also act as important extracellular signaling molecules. We discuss here the broadly expressed P2Y 14 receptor, a G-protein-coupled receptor targeted by UDP sugars, and the increasingly diverse set of physiologic responses discovered recently functioning downstream of this receptor in many epithelia as well as in immune, inflammatory, and other cells.

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Section: Mechanisms Of Release and Metabolism Of Nucleotide Sugarsmentioning

confidence: 74%

UDP-Sugars as Extracellular Signaling Molecules: Cellular and Physiologic Consequences of P2Y₁₄ Receptor Activation

Lazarowski

Harden

2015

Mol Pharmacol

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“…The pannexin-1 channel can be activated by cleavage of its COOH-terminal autoinhibitory domain at a caspase cleavage site by caspase-3 in response to apoptotic stimuli or purified caspase-3 (Sandilos et al, 2012; Boyd-Tressler et al, 2014; Chekeni et al, 2010). We examined whether activation of the noncanonical inflammasome pathway can induce processing of pannexin-1.…”

Section: Resultsmentioning

confidence: 99%

“…In response to apoptotic stimuli, the pannexin-1 channel can be functionally activated by caspase-3-mediated cleavage of the distal end of its autoinhibitory intracellular domain (Sandilos et al, 2012; Boyd-Tressler et al, 2014). Although pannexin-1 has been originally implicated in the formation of the large pore responsible for the enhanced permeation state of P2X7 (Pelegrin and Surprenant, 2006), recent studies reveal that pannexin-1 is dispensable for dye uptake mediated by the P2X7-associated pore and NLRP3 activation in response to ATP (Qu et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Caspase-11 Requires the Pannexin-1 Channel and the Purinergic P2X7 Pore to Mediate Pyroptosis and Endotoxic Shock

et al. 2015

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SUMMARY The noncanonical inflammasome induced by intracellular lipopolysaccharide (LPS) leads to caspase-11-dependent pyroptosis which is critical for induction of endotoxic shock in mice. However, the signaling pathway downstream of caspase-11 is unknown. We found that cytosolic LPS stimulation induced caspase-11-dependent cleavage of the pannexin-1 channel and ATP release, which in turn activated the purinergic P2X7 receptor to mediate cytotoxicity. In the absence of P2X7 or pannexin-1, pyroptosis induced by LPS transfection or treatment with cholera toxin B and LPS was abrogated. Cleavage of pannexin-1 required the catalytic activity of caspase-11 and was essential for ATP release and P2X7-mediated pyroptosis. Priming the caspase-11 pathway in vivo with LPS or toll-like receptor-3 (TLR3) agonist resulted in high mortality in wild-type mice after secondary LPS challenge, but not in Casp11−/−, Panx1−/− or P2x7−/− mice. These results reveal a critical role for pannexin-1 and P2X7 downstream of caspase-11 for pyroptosis and susceptibility to sepsis induced by the noncanonical inflammasome.

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“…With the onset of apoptosis, ATP levels drop and cytoplasm conductivity also drops. 11,34,40 In K562 cells the cytoplasm conductivity dropped from 0.23 S/m to 0.05 S/m with the onset of apoptosis. 11 In apoptosis factors of 3 to 5 drop in potassium are observed.…”

Section: A Dielectric Response Versus Media Conductivitymentioning

confidence: 99%

Monitoring the dielectric response of single cells following mitochondrial adenosine triphosphate synthase inhibition by oligomycin using a dielectrophoretic cytometer

et al. 2014

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One of the main uses of adenosine triphosphate (ATP) within mammalian cells is powering the Na þ /K þ ATPase pumps used to maintain ion concentrations within the cell. Since ion concentrations determine the cytoplasm conductivity, ATP concentration is expected to play a key role in controlling the cytoplasm conductivity. The two major ATP production pathways within cells are via glycolysis within the cytoplasm and via the electron transport chain within the mitochondria. In this work, a differential detector combined with dielectrophoretic (DEP) translation in a microfluidic channel was employed to observe single cell changes in the cytoplasm conductivity. The DEP response was made sensitive to changes in cytoplasm conductivity by measuring DEP response versus media conductivity and using double shell models to choose appropriate frequencies and media conductivity. Dielectric response of Chinese hamster ovary (CHO) cells was monitored following inhibition of the mitochondria ATP production by treatment with oligomycin. We show that in CHO cells following exposure to oligomycin (8 lg/ml) the cytoplasm conductivity drops, with the majority of the change occurring within 50 min. This work demonstrates that dielectric effects due to changes in ATP production can be observed at the single cell level. V C 2014 AIP Publishing LLC.

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Chemotherapeutic Drugs Induce ATP Release via Caspase-gated Pannexin-1 Channels and a Caspase/Pannexin-1-independent Mechanism

Cited by 72 publications

References 83 publications

UDP-Sugars as Extracellular Signaling Molecules: Cellular and Physiologic Consequences of P2Y₁₄ Receptor Activation

UDP-Sugars as Extracellular Signaling Molecules: Cellular and Physiologic Consequences of P2Y₁₄ Receptor Activation

Caspase-11 Requires the Pannexin-1 Channel and the Purinergic P2X7 Pore to Mediate Pyroptosis and Endotoxic Shock

Monitoring the dielectric response of single cells following mitochondrial adenosine triphosphate synthase inhibition by oligomycin using a dielectrophoretic cytometer

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Chemotherapeutic Drugs Induce ATP Release via Caspase-gated Pannexin-1 Channels and a Caspase/Pannexin-1-independent Mechanism

Cited by 72 publications

References 83 publications

UDP-Sugars as Extracellular Signaling Molecules: Cellular and Physiologic Consequences of P2Y14 Receptor Activation

UDP-Sugars as Extracellular Signaling Molecules: Cellular and Physiologic Consequences of P2Y14 Receptor Activation

Caspase-11 Requires the Pannexin-1 Channel and the Purinergic P2X7 Pore to Mediate Pyroptosis and Endotoxic Shock

Monitoring the dielectric response of single cells following mitochondrial adenosine triphosphate synthase inhibition by oligomycin using a dielectrophoretic cytometer

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Product

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UDP-Sugars as Extracellular Signaling Molecules: Cellular and Physiologic Consequences of P2Y₁₄ Receptor Activation

UDP-Sugars as Extracellular Signaling Molecules: Cellular and Physiologic Consequences of P2Y₁₄ Receptor Activation