Metformin protects against intestinal ischemia-reperfusion injury and cell pyroptosis via TXNIP-NLRP3-GSDMD pathway

Jia, Yifan; Cui, Ruixia; Wang, Cong; Yang, Feng; Li, Zeyu; Tong, Yingmu; Qu, Kai; Liu, Chang; Zhang, Jingyao

doi:10.1016/j.redox.2020.101534

Cited by 215 publications

(162 citation statements)

References 34 publications

Supporting

Mentioning

153

Contrasting

Unclassified

Order By: Relevance

“…Subsequent detection of LDH and IL-1 β proved that dioscin reduced LPS+ATP-induced mMEC pyroptosis. Studies have proven that GSDMD is an indispensable factor in the occurrence of cell pyroptosis [ 51 ]. The N-terminal GSDMD fragment mediates the formation of cell membrane pores and directly triggers the occurrence of cell pyroptosis [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Dioscin Improves Pyroptosis in LPS-Induced Mice Mastitis by Activating AMPK/Nrf2 and Inhibiting the NF-κB Signaling Pathway

Ran

Zhang

Yang

et al. 2020

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Dioscin, a natural steroid saponin, has been shown to have anti-inflammatory effects, but its protective mechanism against mastitis is still unknown. NLRP3 inflammasome and pyroptosis play important roles in the pathogenesis of many inflammatory diseases, including mastitis. The purpose of this study was to explore the effect of dioscin on lipopolysaccharide- (LPS-) induced mastitis in vivo and in vitro and its mechanism of action. In vivo experiments, dioscin can reduce the inflammatory lesions and neutrophil motility in mammary tissue. Moreover, dioscin also can reduce the production of proinflammatory factors such as interleukin-1 beta (IL-1β) and inhibit the activation of NLRP3 inflammasome in LPS-induced mice mastitis. In vitro experiments, the results showed that dioscin inhibited the inflammatory response and the activation of NLRP3 inflammasome, but the survival rate of mouse mammary epithelial cells (mMECs) induced by LPS+ATP is increased. Subsequently, the experiment convinces that dioscin can reduce LPS+ATP-induced mMEC pyroptosis by adding Ac-DEVD-CHO (a caspase-3 inhibitor). Further mechanistic studies demonstrate that dioscin can activate AMPK/Nrf2 to inhibit NLRP3/GSDMD-induced mMEC pyroptosis. In summary, this paper reveals a novel function of dioscin on mMEC pyroptosis and provides a new potential therapy of dioscin for the treatment and prevention of mastitis.

show abstract

Section: Discussionmentioning

confidence: 99%

Dioscin Improves Pyroptosis in LPS-Induced Mice Mastitis by Activating AMPK/Nrf2 and Inhibiting the NF-κB Signaling Pathway

Ran

Zhang

Yang

et al. 2020

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…Explosive oxidative stress and inflammation response caused by various abnormal stimuli are common in the pathological process of IRI. Excessive accumulation of reactive oxygen species (ROS) and reactive nitrogen species are important pathological factors causing IRI in various organs, including retina, cerebral, myocardial, liver, kidney, lung and intestine ( Jia et al, 2019 , 2020 ; Li et al, 2020 ; Li et al, 2019d ; Lonati et al, 2019 ; Qin et al, 2019 ; Yi et al, 2020 ). Oxidative stress may promote the expression of pro-inflammatory regulatory factors, and inflammatory cells may similarly induce the overproduction of ROS, thus forming a vicious circle to promote the occurrence and development of various diseases, including IRI.…”

Section: Discussionmentioning

confidence: 99%

“…We have also proven the protective effects of TRAF2 in intestinal IRI, which occurs in a wide variety of clinical conditions, including hemorrhagic shock, acute mesenteric ischemia, and organ transplantation, resulting in a high mortality rate that range from 70 to 80% (Higuchi et al, 2008;Jia et al, 2020). In our research, we verified that PKCζ, a member of the atypical protein kinase C (aPKC) subfamily, phosphorylated TRAF2 at Ser 55 , rather than at Ser 11 , activating NF-κB but inhibiting c-Jun to attenuate cell apoptosis, leading to protection against the injury induced by intestinal ischemia-reperfusion (Zhou W. et al, 2017).…”

Section: Traf2mentioning

confidence: 99%

Roles of TRAFs in Ischemia-Reperfusion Injury

Wei

Lin

Zhong

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Tumor necrosis factor receptor-associated factor (TRAF) proteins are a family of signaling molecules that function downstream of multiple receptor signaling pathways, and they play a pivotal role in the regulation of intracellular biological progresses. These TRAFdependent signaling pathways and physiological functions have been involved in the occurrence and progression of ischemia-reperfusion injury (IRI), which is a common pathophysiological process that occurs in a wide variety of clinical events, including ischemic shock, organ transplantation, and thrombolytic therapy, resulting in a poor prognosis and high mortality. IRI occurs in multiple organs, including liver, kidney, heart, lung, brain, intestine, and retina. In recent years, mounting compelling evidence has confirmed that the genetic alterations of TRAFs can cause subversive phenotype changes during IRI of those organs. In this review, based on current knowledge, we summarized and analyzed the regulatory effect of TRAFs on the IRI of various organs, providing clear direction and a firm theoretical basis for the development of treatment strategies to manipulate TRAF proteins or TRAF-dependent signaling pathways in IRI-related diseases.

show abstract

“…Metformin, which activates AMPK leading to inhibition of TXNIP expression, has significant activity in inhibiting the activation of the NLRP3 inflammasome complex [ 140 , 141 , 142 ]. Metformin also inhibited the interaction of TXNIP and NLRP3 [ 143 ]. Further studies are needed on human brains from cases with diabetes to determine whether there is increased expression of TXNIP and whether this is correlated with AD or severity of AD pathology.…”

Section: Txnip Expression In the Brainmentioning

confidence: 99%

Thioredoxin-Interacting Protein (TXNIP) with Focus on Brain and Neurodegenerative Diseases

Tsubaki

Tooyama

Walker

2020

IJMS

View full text Add to dashboard Cite

The development of new therapeutic approaches to diseases relies on the identification of key molecular targets involved in amplifying disease processes. One such molecule is thioredoxin-interacting protein (TXNIP), also designated thioredoxin-binding protein-2 (TBP-2), a member of the α-arrestin family of proteins and a central regulator of glucose and lipid metabolism, involved in diabetes-associated vascular endothelial dysfunction and inflammation. TXNIP sequesters reduced thioredoxin (TRX), inhibiting its function, resulting in increased oxidative stress. Many different cellular stress factors regulate TXNIP expression, including high glucose, endoplasmic reticulum stress, free radicals, hypoxia, nitric oxide, insulin, and adenosine-containing molecules. TXNIP is also directly involved in inflammatory activation through its interaction with the nucleotide-binding domain, leucine-rich-containing family, and pyrin domain-containing-3 (NLRP3) inflammasome complex. Neurodegenerative diseases such as Alzheimer’s disease have significant pathologies associated with increased oxidative stress, inflammation, and vascular dysfunctions. In addition, as dysfunctions in glucose and cellular metabolism have been associated with such brain diseases, a role for TXNIP in neurodegeneration has actively been investigated. In this review, we will focus on the current state of the understanding of possible normal and pathological functions of TXNIP in the central nervous system from studies of in vitro neural cells and the brains of humans and experimental animals with reference to other studies. As TXNIP can be expressed by neurons, microglia, astrocytes, and endothelial cells, a complex pattern of regulation and function in the brain is suggested. We will examine data suggesting TXNIP as a therapeutic target for neurodegenerative diseases where further research is needed.

show abstract

Metformin protects against intestinal ischemia-reperfusion injury and cell pyroptosis via TXNIP-NLRP3-GSDMD pathway

Cited by 215 publications

References 34 publications

Dioscin Improves Pyroptosis in LPS-Induced Mice Mastitis by Activating AMPK/Nrf2 and Inhibiting the NF-κB Signaling Pathway

Dioscin Improves Pyroptosis in LPS-Induced Mice Mastitis by Activating AMPK/Nrf2 and Inhibiting the NF-κB Signaling Pathway

Roles of TRAFs in Ischemia-Reperfusion Injury

Thioredoxin-Interacting Protein (TXNIP) with Focus on Brain and Neurodegenerative Diseases

Contact Info

Product

Resources

About