Dual regulation of hepatocyte apoptosis by reactive oxygen species: Increases in transcriptional expression and decreases in proteasomal degradation of BimEL

2011 ◽  
Vol 226 (4) ◽  
pp. 1007-1016 ◽  
Author(s):  
Yasuhiro Ishihara ◽  
Kenji Takeuchi ◽  
Fumiaki Ito ◽  
Norio Shimamoto
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Proteasomal Degradation ◽  
Oxygen Species ◽  
Transcriptional Expression ◽  
Hepatocyte Apoptosis

scholarly journals Icarisid I specifically facilitates ATP or nigericin-induced NLRP3 inflammasome activation and causes idiosyncratic hepatotoxicity

2020 ◽  
Author(s):  
Yuan Gao ◽  
Guang Xu ◽  
Li Ma ◽  
Wei Shi ◽  
Zhilei Wang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Liver Injury ◽  
Nlrp3 Inflammasome ◽  
Bone Fractures ◽  
Reactive Oxygen ◽  
Inflammasome Activation ◽  
Oxygen Species ◽  
Hepatocyte Apoptosis ◽  
Specific Stimulus ◽  
Nlrp3 Inflammasome Activation

Abstract Background Epimedii Folium(EF) is commonly used for treating bone fractures and joint diseases, but the potential hepatotoxicity of EF limits its clinical application. Our previous study confirms that EF could lead to idiosyncratic drug-induced liver injury (IDILI) and hepatocyte apoptosis, but the mechanism remains unknown. Studies have shown that NLRP3 inflammasome plays an important role in the development of various inflammatory diseases such as IDILI. Specific stimulus-induced NLRP3 inflammasome activation may has been a key strategy for lead to liver injury. Therefore, main compounds derived from EF were chosen to test whether the ingredients in EF could activate the NLRP3 inflammasome and to induce IDILI. Methods Mouse were treated with Icariside I, and then stimulated with inflammasome stimuli and assayed for the production of caspase-1 and interleukin 1β (IL-1β) and the release of lactate dehydrogenase (LDH). Determination of intracellular potassium, ASC oligomerization as well as reactive oxygen species (ROS) production were used to evaluate the stimulative mechanism of Icariside I on inflammasome activation. Mouse models of NLRP3 diseases were used to test whether Icariside I has hepatocyte apoptosis effects and promoted NLRP3 inflammasome activation in vivo. Results Icariside I specifically enhances NLRP3 inflammasome activation triggered by ATP or nigericin but not SiO2, poly(I:C) or cytosolic LPS. Additionally, Icariside I does not alter the activation of NLRC4 and AIM2 inflammasomes. Mechanically, Icariside I alone does not induce mitochondrial reactive oxygen species (mtROS), which is one of the critical upstream events of NLRP3 inflammasome activation; however, Icariside I increases mtROS production induced by ATP or nigericin but not SiO2. Importantly, Icariside I leads to liver injury and NLRP3 inflammasome activation in an LPS-mediated susceptibility mouse model of IDILI, but the effect of Icariside I is absent in the LPS-mediated mice model pretreated with MCC950, which is used to mimic knockdown of NLRP3 inflammasome activation. Conclusions Our study reveals that Icariside I specifically facilitates ATP or nigericin-induced NLRP3 inflammasome activation and causes idiosyncratic hepatotoxicity. The findings suggest that Icariside I or EF should be avoided in patients with diseases related to ATP or nigericin-induced NLRP3 inflammasome activation, which may be risk factors for IDILI.

scholarly journals Icariside I specifically facilitates ATP or nigericin-induced NLRP3 inflammasome activation and causes idiosyncratic hepatotoxicity

2020 ◽  
Author(s):  
Yuan Gao ◽  
Zhaofang Bai ◽  
Xiaohe Xiao ◽  
guang Xu ◽  
ming Niu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Liver Injury ◽  
Nlrp3 Inflammasome ◽  
Bone Fractures ◽  
Reactive Oxygen ◽  
Inflammasome Activation ◽  
Oxygen Species ◽  
Hepatocyte Apoptosis ◽  
Specific Stimulus ◽  
Nlrp3 Inflammasome Activation

Abstract Background: Epimedii Folium(EF) is commonly used for treating bone fractures and joint diseases, but the potential hepatotoxicity of EF limits its clinical application. Our previous study confirms that EF could lead to idiosyncratic drug-induced liver injury (IDILI) and hepatocyte apoptosis, but the mechanism remains unknown. Studies have shown that NLRP3 inflammasome plays an important role in the development of various inflammatory diseases such as IDILI. Specific stimulus-induced NLRP3 inflammasome activation may has been a key strategy for lead to liver injury. Therefore, main compounds derived from EF were chosen to test whether the ingredients in EF could activate the NLRP3 inflammasome and to induce IDILI.Methods: Mouse were treated with Icariside I, and then stimulated with inflammasome stimuli and assayed for the production of caspase-1 and interleukin 1β (IL-1β) and the release of lactate dehydrogenase (LDH). Determination of intracellular potassium, ASC oligomerization as well as reactive oxygen species (ROS) production were used to evaluate the stimulative mechanism of Icariside I on inflammasome activation. Mouse models of NLRP3 diseases were used to test whether Icariside I has hepatocyte apoptosis effects and promoted NLRP3 inflammasome activation in vivo.Results: Icariside I specifically enhances NLRP3 inflammasome activation triggered by ATP or nigericin but not SiO2, poly(I:C) or cytosolic LPS. Additionally, Icariside I does not alter the activation of NLRC4 and AIM2 inflammasomes. Mechanically, Icariside I alone does not induce mitochondrial reactive oxygen species (mtROS), which is one of the critical upstream events of NLRP3 inflammasome activation; however, Icariside I increases mtROS production induced by ATP or nigericin but not SiO2. Importantly, Icariside I leads to liver injury and NLRP3 inflammasome activation in an LPS-mediated susceptibility mouse model of IDILI, but the effect of Icariside I is absent in the LPS-mediated mice model pretreated with MCC950, which is used to mimic knockdown of NLRP3 inflammasome activation.Conclusions: Our study reveals that Icariside I specifically facilitates ATP or nigericin-induced NLRP3 inflammasome activation and causes idiosyncratic hepatotoxicity. The findings suggest that Icariside I or EF should be avoided in patients with diseases related to ATP or nigericin-induced NLRP3 inflammasome activation, which may be risk factors for IDILI.

scholarly journals Icarisid I specifically facilitates ATP or nigericin-induced NLRP3 inflammasome activation and causes idiosyncratic hepatotoxicity

2019 ◽  
Author(s):  
Yuan Gao ◽  
Zhaofang Bai ◽  
Xiaohe Xiao ◽  
Guang Xu ◽  
Ming Niu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Liver Injury ◽  
Nlrp3 Inflammasome ◽  
Bone Fractures ◽  
Reactive Oxygen ◽  
Inflammasome Activation ◽  
Oxygen Species ◽  
Hepatocyte Apoptosis ◽  
Specific Stimulus ◽  
Nlrp3 Inflammasome Activation

Abstract Background Epimedii Folium(EF) is commonly used for treating bone fractures and joint diseases, but the potential hepatotoxicity of EF limits its clinical application. Our previous study confirms that EF could lead to idiosyncratic drug-induced liver injury (IDILI) and hepatocyte apoptosis, but the mechanism remains unknown. Studies have shown that NLRP3 inflammasome plays an important role in the development of various inflammatory diseases such as IDILI. Specific stimulus-induced NLRP3 inflammasome activation may has been a key strategy for lead to liver injury. Therefore, main compounds derived from EF were chosen to test whether the ingredients in EF could activate the NLRP3 inflammasome and to induce IDILI.Methods Mouse were treated with Icarisid I, and then stimulated with inflammasome stimuli and assayed for the production of caspase-1 and interleukin 1β (IL-1β) and the release of lactate dehydrogenase (LDH). Determination of intracellular potassium, ASC oligomerization as well as reactive oxygen species (ROS) production were used to evaluate the stimulative mechanism of Icarisid I on inflammasome activation. Mouse models of NLRP3 diseases were used to test whether Icarisid I has hepatocyte apoptosis effects and promoted NLRP3 inflammasome activation in vivo.Results Icarisid I specifically enhances NLRP3 inflammasome activation triggered by ATP or nigericin but not SiO2, poly(I:C) or cytosolic LPS. Additionally, Icarisid I does not alter the activation of NLRC4 and AIM2 inflammasomes. Mechanically, Icarisid I alone does not induce mitochondrial reactive oxygen species (mtROS), which is one of the critical upstream events of NLRP3 inflammasome activation; however, Icarisid I increases mtROS production induced by ATP or nigericin but not SiO2. Importantly, Icarisid I leads to liver injury and NLRP3 inflammasome activation in an LPS-mediated susceptibility mouse model of IDILI, but the effect of Icarisid I is absent in the LPS-mediated mice model pretreated with MCC950, which is used to mimic knockdown of NLRP3 inflammasome activation.Conclusions Our study reveals that Icarisid I specifically facilitates ATP or nigericin-induced NLRP3 inflammasome activation and causes idiosyncratic hepatotoxicity. The findings suggest that Icarisid I or EF should be avoided in patients with diseases related to ATP or nigericin-induced NLRP3 inflammasome activation, which may be risk factors for IDILI.

scholarly journals Icariside I specifically facilitates ATP or nigericin-induced NLRP3 inflammasome activation and causes idiosyncratic hepatotoxicity

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuan Gao ◽  
Guang Xu ◽  
Li Ma ◽  
Wei Shi ◽  
Zhilei Wang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Liver Injury ◽  
Mouse Model ◽  
Nlrp3 Inflammasome ◽  
Reactive Oxygen ◽  
Inflammasome Activation ◽  
Oxygen Species ◽  
Hepatocyte Apoptosis ◽  
Specific Stimulus ◽  
Nlrp3 Inflammasome Activation

Abstract Background Epimedii Folium (EF) is commonly used for treating bone fractures and joint diseases, but the potential hepatotoxicity of EF limits its clinical application. Our previous study confirms that EF could lead to idiosyncratic drug-induced liver injury (IDILI) and hepatocyte apoptosis, but the mechanism remains unknown. Studies have shown that NLRP3 inflammasome plays an important role in the development of various inflammatory diseases such as IDILI. Specific stimulus-induced NLRP3 inflammasome activation may has been a key strategy for lead to liver injury. Therefore, main compounds derived from EF were chosen to test whether the ingredients in EF could activate the NLRP3 inflammasome and to induce IDILI. Methods Bone-marrow-derived macrophages (BMDMs) were treated with Icariside I, and then stimulated with inflammasome stimuli and assayed for the production of caspase-1 and interleukin 1β (IL-1β) and the release of lactate dehydrogenase (LDH). Determination of intracellular potassium, ASC oligomerization as well as reactive oxygen species (ROS) production were used to evaluate the stimulative mechanism of Icariside I on inflammasome activation. Mouse models of NLRP3 diseases were used to test whether Icariside I has hepatocyte apoptosis effects and promoted NLRP3 inflammasome activation in vivo. Results Icariside I specifically enhances NLRP3 inflammasome activation triggered by ATP or nigericin but not SiO2, poly(I:C) or cytosolic LPS. Additionally, Icariside I does not alter the activation of NLRC4 and AIM2 inflammasomes. Mechanically, Icariside I alone does not induce mitochondrial reactive oxygen species (mtROS), which is one of the critical upstream events of NLRP3 inflammasome activation; however, Icariside I increases mtROS production induced by ATP or nigericin but not SiO2. Importantly, Icariside I leads to liver injury and NLRP3 inflammasome activation in an LPS-mediated susceptibility mouse model of IDILI, but the effect of Icariside I is absent in the LPS-mediated mouse model pretreated with MCC950, which is used to mimic knockdown of NLRP3 inflammasome activation. Conclusions Our study reveals that Icariside I specifically facilitates ATP or nigericin-induced NLRP3 inflammasome activation and causes idiosyncratic hepatotoxicity. The findings suggest that Icariside I or EF should be avoided in patients with diseases related to ATP or nigericin-induced NLRP3 inflammasome activation, which may be risk factors for IDILI.

scholarly journals Phosphocreatine attenuates Gynura segetum-induced hepatocyte apoptosis via a SIRT3-SOD2-mitochondrial reactive oxygen species pathway

2019 ◽  
Vol Volume 13 ◽  
pp. 2081-2096 ◽  
Author(s):  
Dong-Ping Li ◽  
Ying-Ling Chen ◽  
Hong-Yue Jiang ◽  
Yun Chen ◽  
Xiao-Qing Zeng ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Hepatocyte Apoptosis

scholarly journals Transforming growth factor beta mediates hepatocyte apoptosis through Smad3 generation of reactive oxygen species

Biochimie ◽  
2007 ◽  
Vol 89 (12) ◽  
pp. 1464-1473 ◽  
Author(s):  
Dalliah Black ◽  
Suzanne Lyman ◽  
Ting Qian ◽  
John J. Lemasters ◽  
Richard A. Rippe ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Hepatocyte Apoptosis ◽  
Growth Factor Beta

Mitochondria as a source of reactive oxygen species

2009 ◽  
pp. c3 ◽  
Author(s):  
Helena M. Cochemé ◽  
Michael P. Murphy
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Oxygen Species
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