Research ExplorerPublicationsShort Exposure to Ethanol Diminishes Caspase-1 and ASC Activ...

Short Exposure to Ethanol Diminishes Caspase-1 and ASC Activation in Human HepG2 Cells In Vitro

Standard

Short Exposure to Ethanol Diminishes Caspase-1 and ASC Activation in Human HepG2 Cells In Vitro. / Hörauf, Jason-Alexander; Kany, Shinwan; Janicova, Andrea; Xu, Baolin; Vrdoljak, Teodora; Sturm, Ramona; Dunay, Ildiko Rita; Martin, Lukas; Relja, Borna.

In: INT J MOL SCI, Vol. 21, No. 9, 3196, 01.05.2020.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Hörauf, J-A, Kany, S, Janicova, A, Xu, B, Vrdoljak, T, Sturm, R, Dunay, IR, Martin, L & Relja, B 2020, 'Short Exposure to Ethanol Diminishes Caspase-1 and ASC Activation in Human HepG2 Cells In Vitro', INT J MOL SCI, vol. 21, no. 9, 3196. https://doi.org/10.3390/ijms21093196

APA

Hörauf, J-A., Kany, S., Janicova, A., Xu, B., Vrdoljak, T., Sturm, R., Dunay, I. R., Martin, L., & Relja, B. (2020). Short Exposure to Ethanol Diminishes Caspase-1 and ASC Activation in Human HepG2 Cells In Vitro. INT J MOL SCI, 21(9), [3196]. https://doi.org/10.3390/ijms21093196

Vancouver

Hörauf J-A, Kany S, Janicova A, Xu B, Vrdoljak T, Sturm R et al. Short Exposure to Ethanol Diminishes Caspase-1 and ASC Activation in Human HepG2 Cells In Vitro. INT J MOL SCI. 2020 May 1;21(9). 3196. https://doi.org/10.3390/ijms21093196

Bibtex

@article{c043cf4cc41d454184576b8597aa982d,
title = "Short Exposure to Ethanol Diminishes Caspase-1 and ASC Activation in Human HepG2 Cells In Vitro",
abstract = "This paper discusses how the assembly of pro-caspase-1 and apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) in macromolecular protein complexes, inflammasomes, activates caspase-1. The present study investigates the molecular mechanisms of inflammasome activation in HepG2 cells and examines how short exposures to ethanol (EtOH) affect inflammasome activation. HepG2 cells were treated with lipopolysaccharide (LPS), ATP or nigericin (NIG) in a two-step model. After LPS priming, ATP or NIG were added. As inhibitors, sodium orthovanadate (general inhibitor of tyrosine phosphatases), AC-YVAD-CMK (caspase-1 inhibitor) or AZ10606120 (purinergic receptor P2X7R inhibitor) were applied after LPS priming. To monitor the inflammasome activation, the caspase-1 activity, ASC speck formation, reactive oxygen species (ROS) production and cell death were analyzed. To elucidate the mechanistical approach of EtOH to the inflammasome assembly, the cells were treated with EtOH either under simultaneous LPS administration or concurrently with ATP or NIG application. The co-stimulation with LPS and ATP induced a significant ASC speck formation, caspase-1 activation, cell death and ROS generation. The inhibition of the ATP-dependent purinoreceptor P2X7 decreased the caspase-1 activation, whereas sodium orthovanadate significantly induced caspase-1. Additional treatment with EtOH reversed the LPS and ATP-induced caspase-1 activation, ASC speck formation and ROS production. The ASC speck formation and caspase-1 induction require a two-step signaling with LPS and ATP in HepG2 cells. Inflammasome activation may depend on P2X7. The molecular pathway of an acute effect of EtOH on inflammasomes may involve a reduction in ROS generation, which in turn may increase the activity of tyrosine phosphatases.",
keywords = "Adamantane/analogs & derivatives, Amino Acid Chloromethyl Ketones/pharmacology, Aminoquinolines/pharmacology, Caspase 1/metabolism, Ethanol/pharmacology, Hep G2 Cells, Humans, Inflammasomes/drug effects, Lipopolysaccharides/pharmacology, Liver/drug effects, Reactive Oxygen Species/metabolism, Vanadates/pharmacology",
author = "Jason-Alexander H{\"o}rauf and Shinwan Kany and Andrea Janicova and Baolin Xu and Teodora Vrdoljak and Ramona Sturm and Dunay, {Ildiko Rita} and Lukas Martin and Borna Relja",
year = "2020",
month = may,
day = "1",
doi = "10.3390/ijms21093196",
language = "English",
volume = "21",
journal = "INT J MOL SCI",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "9",

}

RIS

TY - JOUR

T1 - Short Exposure to Ethanol Diminishes Caspase-1 and ASC Activation in Human HepG2 Cells In Vitro

AU - Hörauf, Jason-Alexander

AU - Kany, Shinwan

AU - Janicova, Andrea

AU - Xu, Baolin

AU - Vrdoljak, Teodora

AU - Sturm, Ramona

AU - Dunay, Ildiko Rita

AU - Martin, Lukas

AU - Relja, Borna

PY - 2020/5/1

Y1 - 2020/5/1

N2 - This paper discusses how the assembly of pro-caspase-1 and apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) in macromolecular protein complexes, inflammasomes, activates caspase-1. The present study investigates the molecular mechanisms of inflammasome activation in HepG2 cells and examines how short exposures to ethanol (EtOH) affect inflammasome activation. HepG2 cells were treated with lipopolysaccharide (LPS), ATP or nigericin (NIG) in a two-step model. After LPS priming, ATP or NIG were added. As inhibitors, sodium orthovanadate (general inhibitor of tyrosine phosphatases), AC-YVAD-CMK (caspase-1 inhibitor) or AZ10606120 (purinergic receptor P2X7R inhibitor) were applied after LPS priming. To monitor the inflammasome activation, the caspase-1 activity, ASC speck formation, reactive oxygen species (ROS) production and cell death were analyzed. To elucidate the mechanistical approach of EtOH to the inflammasome assembly, the cells were treated with EtOH either under simultaneous LPS administration or concurrently with ATP or NIG application. The co-stimulation with LPS and ATP induced a significant ASC speck formation, caspase-1 activation, cell death and ROS generation. The inhibition of the ATP-dependent purinoreceptor P2X7 decreased the caspase-1 activation, whereas sodium orthovanadate significantly induced caspase-1. Additional treatment with EtOH reversed the LPS and ATP-induced caspase-1 activation, ASC speck formation and ROS production. The ASC speck formation and caspase-1 induction require a two-step signaling with LPS and ATP in HepG2 cells. Inflammasome activation may depend on P2X7. The molecular pathway of an acute effect of EtOH on inflammasomes may involve a reduction in ROS generation, which in turn may increase the activity of tyrosine phosphatases.

AB - This paper discusses how the assembly of pro-caspase-1 and apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) in macromolecular protein complexes, inflammasomes, activates caspase-1. The present study investigates the molecular mechanisms of inflammasome activation in HepG2 cells and examines how short exposures to ethanol (EtOH) affect inflammasome activation. HepG2 cells were treated with lipopolysaccharide (LPS), ATP or nigericin (NIG) in a two-step model. After LPS priming, ATP or NIG were added. As inhibitors, sodium orthovanadate (general inhibitor of tyrosine phosphatases), AC-YVAD-CMK (caspase-1 inhibitor) or AZ10606120 (purinergic receptor P2X7R inhibitor) were applied after LPS priming. To monitor the inflammasome activation, the caspase-1 activity, ASC speck formation, reactive oxygen species (ROS) production and cell death were analyzed. To elucidate the mechanistical approach of EtOH to the inflammasome assembly, the cells were treated with EtOH either under simultaneous LPS administration or concurrently with ATP or NIG application. The co-stimulation with LPS and ATP induced a significant ASC speck formation, caspase-1 activation, cell death and ROS generation. The inhibition of the ATP-dependent purinoreceptor P2X7 decreased the caspase-1 activation, whereas sodium orthovanadate significantly induced caspase-1. Additional treatment with EtOH reversed the LPS and ATP-induced caspase-1 activation, ASC speck formation and ROS production. The ASC speck formation and caspase-1 induction require a two-step signaling with LPS and ATP in HepG2 cells. Inflammasome activation may depend on P2X7. The molecular pathway of an acute effect of EtOH on inflammasomes may involve a reduction in ROS generation, which in turn may increase the activity of tyrosine phosphatases.

KW - Adamantane/analogs & derivatives

KW - Amino Acid Chloromethyl Ketones/pharmacology

KW - Aminoquinolines/pharmacology

KW - Caspase 1/metabolism

KW - Ethanol/pharmacology

KW - Hep G2 Cells

KW - Humans

KW - Inflammasomes/drug effects

KW - Lipopolysaccharides/pharmacology

KW - Liver/drug effects

KW - Reactive Oxygen Species/metabolism

KW - Vanadates/pharmacology

U2 - 10.3390/ijms21093196

DO - 10.3390/ijms21093196

M3 - SCORING: Journal article

C2 - 32366053

VL - 21

JO - INT J MOL SCI

JF - INT J MOL SCI

SN - 1661-6596

IS - 9

M1 - 3196

ER -