Amphotericin B Increases Transglutaminase 2 Expression Associated with Upregulation of Endocytotic Activity in Mouse Microglial Cell Line BV-2

Kawabe, Kentaro; Takano, Katsura; Moriyama, Mitsuaki; Nakamura, Yoichi

doi:10.1007/s11064-017-2205-0

Cited by 8 publications

(6 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previously, it has been reported that an increase of TGM2 expression facilitates the generation of inducible nitric oxide synthase (iNOS), which might induce neuronal death [ 20 ]. Therefore, controlling TGM2 activity might provide an approach to protect neurons and care for CNS injuries [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Propofol Suppresses Microglia Inflammation by Targeting TGM2/NF-κB Signaling

Hou

Xiao

et al. 2021

Journal of Immunology Research

View full text Add to dashboard Cite

Background. Propofol is a known intravenous hypnotic drug used for induction and maintenance of sedation and general anesthesia. Emerging studies also reveal a neuroprotective effect of propofol in diverse diseases of neuronal injuries via modulating microglia activation. In this study, we aimed to uncover the downstream targets of propofol in this process. Methods. RNA sequencing analysis to identify genes implicated in the propofol-mediated neuroprotective effect. Quantitative real-time PCR, enzyme-linked immunosorbent assay, and Western blotting analysis were performed to analyze inflammatory gene expression, cytokine levels, and TGM2. BV2 cells and primary microglia were used for functional verification and mechanism studies. Results. The multifunctional enzyme transglutaminase 2 (TGM2) was identified as a putative functional mediator of propofol. TGM2 was significantly upregulated in lipopolysaccharide- (LPS-) primed BV2 cells. Genetic silencing of TGM2 abolished LPS-induced microglial activation. Notably, gain-of-function experiments showed that the proinflammatory effects of TGM2 were dependent on its GTP binding activity instead of transamidase activity. Then, TGM2 was revealed to activate the NF-κB signaling pathway to facilitate microglial activation. Propofol can inhibit TGM2 expression and NF-κB signaling in BV2 cells and primary microglia. Ectopic expression of TGM2 or constitutively active IKKβ (CA-IKKβ) can compromise propofol-induced anti-inflammatory effects. Conclusions. Our findings suggest that TGM2-mediated activation of NF-κB signaling is an important mechanism in the propofol-induced neuroprotective effect that prevents microglial activation.

show abstract

Section: Introductionmentioning

confidence: 99%

Propofol Suppresses Microglia Inflammation by Targeting TGM2/NF-κB Signaling

Hou

Xiao

et al. 2021

Journal of Immunology Research

View full text Add to dashboard Cite

show abstract

“…In the previous study, we reported in activated microglia that TG2 might be involved in endocytosis of fluorescent beads and dead cells, because of inhibition of the endocytosis by cystamine, an inhibitor of TG enzyme activity [39,40]. Cystamine also inhibited LPS-increased TG2 expression, iNOS expression, and NO production [39].…”

Section: Introductionmentioning

confidence: 92%

Microglial endocytosis and transglutaminases

Kawabe¹,

Takano²

2017

Glob Drugs Therap

Self Cite

View full text Add to dashboard Cite

“…For example, NO downregulates endocytosis in rat liver endothelial cells ( Martinez et al, 1996 ) but promotes caveolae-mediated endocytosis as mentioned above ( Chen et al, 2018 ). Macrophages stimulated by the thymic peptide thyαl display enhanced NO levels as well as increased pinocytosis ( Shrivastava et al, 2004 ), as do amphotericin B-stimulated microglial cells ( Kawabe et al, 2017 ). Conversely, mouse peritoneal macrophages stimulated with activin A display both reduced NO and pinocytosis ( Zhou et al, 2009 ).…”

Section: Water Ions and Their Channels And Transporters In Pinocytosismentioning

confidence: 99%

From Pinocytosis to Methuosis—Fluid Consumption as a Risk Factor for Cell Death

Ritter

Bresgen

Kerschbaum

2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The volumes of a cell [cell volume (CV)] and its organelles are adjusted by osmoregulatory processes. During pinocytosis, extracellular fluid volume equivalent to its CV is incorporated within an hour and membrane area equivalent to the cell’s surface within 30 min. Since neither fluid uptake nor membrane consumption leads to swelling or shrinkage, cells must be equipped with potent volume regulatory mechanisms. Normally, cells respond to outwardly or inwardly directed osmotic gradients by a volume decrease and increase, respectively, i.e., they shrink or swell but then try to recover their CV. However, when a cell death (CD) pathway is triggered, CV persistently decreases in isotonic conditions in apoptosis and it increases in necrosis. One type of CD associated with cell swelling is due to a dysfunctional pinocytosis. Methuosis, a non-apoptotic CD phenotype, occurs when cells accumulate too much fluid by macropinocytosis. In contrast to functional pinocytosis, in methuosis, macropinosomes neither recycle nor fuse with lysosomes but with each other to form giant vacuoles, which finally cause rupture of the plasma membrane (PM). Understanding methuosis longs for the understanding of the ionic mechanisms of cell volume regulation (CVR) and vesicular volume regulation (VVR). In nascent macropinosomes, ion channels and transporters are derived from the PM. Along trafficking from the PM to the perinuclear area, the equipment of channels and transporters of the vesicle membrane changes by retrieval, addition, and recycling from and back to the PM, causing profound changes in vesicular ion concentrations, acidification, and—most importantly—shrinkage of the macropinosome, which is indispensable for its proper targeting and cargo processing. In this review, we discuss ion and water transport mechanisms with respect to CVR and VVR and with special emphasis on pinocytosis and methuosis. We describe various aspects of the complex mutual interplay between extracellular and intracellular ions and ion gradients, the PM and vesicular membrane, phosphoinositides, monomeric G proteins and their targets, as well as the submembranous cytoskeleton. Our aim is to highlight important cellular mechanisms, components, and processes that may lead to methuotic CD upon their derangement.

show abstract

Amphotericin B Increases Transglutaminase 2 Expression Associated with Upregulation of Endocytotic Activity in Mouse Microglial Cell Line BV-2

Cited by 8 publications

References 32 publications

Propofol Suppresses Microglia Inflammation by Targeting TGM2/NF-κB Signaling

Propofol Suppresses Microglia Inflammation by Targeting TGM2/NF-κB Signaling

Microglial endocytosis and transglutaminases

From Pinocytosis to Methuosis—Fluid Consumption as a Risk Factor for Cell Death

Contact Info

Product

Resources

About