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An Inhibitor of DRP1 (Mdivi-1) Alleviates LPS-Induced Septic AKI by Inhibiting NLRP3 Inflammasome Activation
by
Liu, Ruijin
, Li, Ming
, Ma, Xiao-hui
, Yu, Kai-jiang
, Sun, Lei
, Bu, Yue
, Jia, Xiao-nan
, Wang, Si-cong
in
Acute Kidney Injury - complications
/ Acute Kidney Injury - drug therapy
/ Acute Kidney Injury - pathology
/ Animals
/ Apoptosis
/ Apoptosis - drug effects
/ Cell culture
/ Cell Line
/ Deprivation
/ Disease Models, Animal
/ Down-Regulation - drug effects
/ Dynamin
/ Dynamins - metabolism
/ Energy metabolism
/ Fission
/ Free radicals
/ Gene expression
/ Inflammasomes
/ Inflammasomes - metabolism
/ Kidney Tubules - drug effects
/ Kidney Tubules - pathology
/ Kidneys
/ Kinases
/ Lipopolysaccharides
/ Male
/ Mice, Inbred C57BL
/ Mitochondria
/ Mitochondria - drug effects
/ Mitochondria - metabolism
/ Mitochondrial DNA
/ NLR Family, Pyrin Domain-Containing 3 Protein - metabolism
/ Oxidative Stress - drug effects
/ Protein turnover
/ Proteins
/ Proximal tubules
/ Pyrin protein
/ Pyroptosis
/ Quinazolinones - pharmacology
/ Quinazolinones - therapeutic use
/ Renal tubules
/ RNA, Small Interfering - metabolism
/ Sepsis
/ Sepsis - complications
/ Sepsis - drug therapy
/ Sepsis - pathology
2020
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An Inhibitor of DRP1 (Mdivi-1) Alleviates LPS-Induced Septic AKI by Inhibiting NLRP3 Inflammasome Activation
by
Liu, Ruijin
, Li, Ming
, Ma, Xiao-hui
, Yu, Kai-jiang
, Sun, Lei
, Bu, Yue
, Jia, Xiao-nan
, Wang, Si-cong
in
Acute Kidney Injury - complications
/ Acute Kidney Injury - drug therapy
/ Acute Kidney Injury - pathology
/ Animals
/ Apoptosis
/ Apoptosis - drug effects
/ Cell culture
/ Cell Line
/ Deprivation
/ Disease Models, Animal
/ Down-Regulation - drug effects
/ Dynamin
/ Dynamins - metabolism
/ Energy metabolism
/ Fission
/ Free radicals
/ Gene expression
/ Inflammasomes
/ Inflammasomes - metabolism
/ Kidney Tubules - drug effects
/ Kidney Tubules - pathology
/ Kidneys
/ Kinases
/ Lipopolysaccharides
/ Male
/ Mice, Inbred C57BL
/ Mitochondria
/ Mitochondria - drug effects
/ Mitochondria - metabolism
/ Mitochondrial DNA
/ NLR Family, Pyrin Domain-Containing 3 Protein - metabolism
/ Oxidative Stress - drug effects
/ Protein turnover
/ Proteins
/ Proximal tubules
/ Pyrin protein
/ Pyroptosis
/ Quinazolinones - pharmacology
/ Quinazolinones - therapeutic use
/ Renal tubules
/ RNA, Small Interfering - metabolism
/ Sepsis
/ Sepsis - complications
/ Sepsis - drug therapy
/ Sepsis - pathology
2020
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An Inhibitor of DRP1 (Mdivi-1) Alleviates LPS-Induced Septic AKI by Inhibiting NLRP3 Inflammasome Activation
by
Liu, Ruijin
, Li, Ming
, Ma, Xiao-hui
, Yu, Kai-jiang
, Sun, Lei
, Bu, Yue
, Jia, Xiao-nan
, Wang, Si-cong
in
Acute Kidney Injury - complications
/ Acute Kidney Injury - drug therapy
/ Acute Kidney Injury - pathology
/ Animals
/ Apoptosis
/ Apoptosis - drug effects
/ Cell culture
/ Cell Line
/ Deprivation
/ Disease Models, Animal
/ Down-Regulation - drug effects
/ Dynamin
/ Dynamins - metabolism
/ Energy metabolism
/ Fission
/ Free radicals
/ Gene expression
/ Inflammasomes
/ Inflammasomes - metabolism
/ Kidney Tubules - drug effects
/ Kidney Tubules - pathology
/ Kidneys
/ Kinases
/ Lipopolysaccharides
/ Male
/ Mice, Inbred C57BL
/ Mitochondria
/ Mitochondria - drug effects
/ Mitochondria - metabolism
/ Mitochondrial DNA
/ NLR Family, Pyrin Domain-Containing 3 Protein - metabolism
/ Oxidative Stress - drug effects
/ Protein turnover
/ Proteins
/ Proximal tubules
/ Pyrin protein
/ Pyroptosis
/ Quinazolinones - pharmacology
/ Quinazolinones - therapeutic use
/ Renal tubules
/ RNA, Small Interfering - metabolism
/ Sepsis
/ Sepsis - complications
/ Sepsis - drug therapy
/ Sepsis - pathology
2020
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An Inhibitor of DRP1 (Mdivi-1) Alleviates LPS-Induced Septic AKI by Inhibiting NLRP3 Inflammasome Activation
Journal Article
An Inhibitor of DRP1 (Mdivi-1) Alleviates LPS-Induced Septic AKI by Inhibiting NLRP3 Inflammasome Activation
2020
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Overview
Mitochondria play an essential role in energy metabolism. Oxygen deprivation can poison cells and generate a chain reaction due to the free radical release. In patients with sepsis, the kidneys tend to be the organ primarily affected and the proximal renal tubules are highly susceptible to energy metabolism imbalances. Dynamin-related protein 1 (DRP1) is an essential regulator of mitochondrial fission. Few studies have confirmed the role and mechanism of DRP1 in acute kidney injury (AKI) caused by sepsis. We established animal and cell sepsis-induced AKI (S-AKI) models to keep DRP1 expression high. We found that Mdivi-1, a DRP1 inhibitor, can reduce the activation of the NOD-like receptor pyrin domain-3 (NLRP3) inflammasome-mediated pyroptosis pathway and improve mitochondrial function. Both S-AKI models showed that Mdivi-1 was able to prevent the mitochondrial content release and decrease the expression of NLRP3 inflammasome-related proteins. In addition, silencing NLRP3 gene expression further emphasized the pyroptosis importance in S-AKI occurrence. Our results indicate that the possible mechanism of action of Mdivi-1 is to inhibit mitochondrial fission and protect mitochondrial function, thereby reducing pyroptosis. These data can provide a potential theoretical basis for Mdivi-1 potential use in the S-AKI prevention.
Publisher
Hindawi Publishing Corporation,Hindawi,John Wiley & Sons, Inc
Subject
Acute Kidney Injury - complications
/ Acute Kidney Injury - drug therapy
/ Acute Kidney Injury - pathology
/ Animals
/ Down-Regulation - drug effects
/ Dynamin
/ Fission
/ Kidney Tubules - drug effects
/ Kidneys
/ Kinases
/ Male
/ NLR Family, Pyrin Domain-Containing 3 Protein - metabolism
/ Oxidative Stress - drug effects
/ Proteins
/ Quinazolinones - pharmacology
/ Quinazolinones - therapeutic use
/ RNA, Small Interfering - metabolism
/ Sepsis
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