Adiponectin inhibits inflammatory cytokines production by Beclin‐1 phosphorylation and B‐cell lymphoma 2 mRNA destabilization: role for autophagy induction

Pun, Nirmala Tilija; Park, Pil-Hoon

doi:10.1111/bph.14144

Cited by 23 publications

(21 citation statements)

References 67 publications

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“…We have recently demonstrated that globular adiponectin (gAcrp) induces destabilization of Bcl-2 mRNA through TTP induction ( Tilija Pun and Park, 2018 ). Stability of the mRNA is modulated by a number of AU-rich element mRNA binding proteins (AUBPs).…”

Section: Discussionmentioning

confidence: 99%

“…Adiponectin has been shown to decrease Bcl-2 expression in macrophages and cancer cells ( Mistry et al ., 2008 ; Tilija Pun and Park, 2018 ). We have previously shown that TTP induction contributes to adiponectin-induced Bcl-2 mRNA destabilization in macrophages ( Tilija Pun and Park, 2018 ). To date, in addition to TTP, a number of different types of AUBPs have been identified and modulates mRNA decay in a gene-selective manner.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, association of Beclin-1 with Bcl-2 is a critical factor for the modulation of autophagy induction. Recently, it has been reported that gAcrp induces autophagy in macrophages by Bcl-2 mRNA destabilization and modulating association of Bcl-2 and Beclin-1 ( Tilija Pun and Park, 2018 ). Given that association of Beclin-1 and Bcl-2 is a critical event modulating autophagy induction, suppression of Bcl-2 expression would be a critical event leading to autophagy induction and further anti-inflammatory responses by adiponectin.…”

Section: Introductionmentioning

confidence: 99%

“…For example, binding of HuR and nucleolin induces Bcl-2 mRNA stabilization ( Ishimaru et al ., 2009 , 2010 ), while binding of triestetraproline, (TTP), ARE/poly (U)-binding factor 1 (AUF1), and zinc finger RNA binding protein like 1 (ZFP36L1) results in mRNA destabilization of the target mRNA ( Dodson and Shapiro, 2002 ). We have previously shown that induction of tristetraproln (TTP), acting as a mRNA destabilizer, contributes to adiponectin-induced decrease in Bcl-2 expression in macrophages ( Tilija Pun and Park, 2018 ). To date, in addition to TTP, a number of different types of mRNA binding proteins have been identified and are implicated in modulating decay of mRNA in a gene-selective manner.…”

Section: Introductionmentioning

confidence: 99%

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ZFP36L1 and AUF1 Induction Contribute to the Suppression of Inflammatory Mediators Expression by Globular Adiponectin via Autophagy Induction in Macrophages

Shrestha

Pun

Park

2018

Biomol Ther (Seoul)

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Adiponectin, a hormone predominantly originated from adipose tissue, has exhibited potent anti-inflammatory properties. Accumulating evidence suggests that autophagy induction plays a crucial role in anti-inflammatory responses by adiponectin. However, underlying molecular mechanisms are still largely unknown. Association of Bcl-2 with Beclin-1, an autophagy activating protein, prevents autophagy induction. We have previously shown that adiponectin-induced autophagy activation is mediated through inhibition of interaction between Bcl-2 and Beclin-1. In the present study, we examined the molecular mechanisms by which adiponectin modulates association of Bcl-2 and Beclin-1 in macrophages. Herein, we demonstrated that globular adiponectin (gAcrp) induced increase in the expression of AUF1 and ZFP36L1, which act as mRNA destabilizing proteins, both in RAW 264.7 macrophages and primary peritoneal macrophages. In addition, gene silencing of AUF1 and ZFP36L1 caused restoration of decrease in Bcl-2 expression and Bcl-2 mRNA half-life by gAcrp, indicating crucial roles of AUF1 and ZFP36L1 induction in Bcl-2 mRNA destabilization by gAcrp. Moreover, knock-down of AUF1 and ZFP36L1 enhanced interaction of Bcl-2 with Beclin-1, and subsequently prevented gAcrp-induced autophagy activation, suggesting that AUF1 and ZFP36L1 induction mediates gAcrp-induced autophagy activation via Bcl-2 mRNA destabilization. Furthermore, suppressive effects of gAcrp on LPS-stimulated inflammatory mediators expression were prevented by gene silencing of AUF1 and ZFP36L1 in macrophages. Taken together, these results suggest that AUF1 and ZFP36L1 induction critically contributes to autophagy induction by gAcrp and are promising targets for anti-inflammatory responses by gAcrp.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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ZFP36L1 and AUF1 Induction Contribute to the Suppression of Inflammatory Mediators Expression by Globular Adiponectin via Autophagy Induction in Macrophages

Shrestha

Pun

Park

2018

Biomol Ther (Seoul)

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“…Mice were anaesthetized with isoflurane, followed by an immediate cervical dislocation. Murine peritoneal macrophages were isolated as previously described (Tilija Pun & Park, ). Briefly, cells were elicited by injection of 1 ml of 3.8% sterile thioglycollate medium (BD Biosciences, San Jose, CA, USA) into the peritoneal cavity.…”

Section: Methodsmentioning

confidence: 99%

P2X7 receptor‐targeted regulation by tetrahydroxystilbene glucoside in alcoholic hepatosteatosis: A new strategy towards macrophage–hepatocyte crosstalk

Zhang

Jiang

Cui

et al. 2020

British J Pharmacology

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Background and Purpose:Regulating macrophage-hepatocyte crosstalk through P2X7 receptors has led to new pharmacological strategies to reverse alcoholic hepatosteatosis. We investigated how tetrahydroxystilbene glucoside (2354glu), isolated from Polygonum multiflorum, modulates macrophage-hepatocyte crosstalk during alcoholic hepatosteatosis.Experimental Approach: A model of alcoholic hepatosteatosis was established by giving ethanol intragastrically to C57BL/6 mice. HepG2 cells were incubated in conditioned medium from LPS+ATP-activated THP-1 human macrophages with silenced or overexpressed P2X7 receptors. THP-1 macrophages or mouse peritoneal macrophages were pretreated with 2354glu for 1 hr prior to LPS+ATP stimulation.Western blots, RT-PCR and immunohistochemical analysis were used, along with over-expression and silencing of P2X7 receptors.Key Results: Knockdown or overexpression of P2X7 receptors in THP-1 macrophages affected release of mature IL-1β and, subsequently, modulated lipid metabolism in HepG2 cells via the LKB-AMPK pathway. 2354glu ameliorated alcoholic hepatosteatosis in mice by regulating LKB1-AMPK-SREBP1 pathway and its target genes. Suppression of P2X7 receptor activation by 2354glu inhibited IL-1β release and reduced macrophage and neutrophil infiltration. In macrophages stimulated with LPS+ATP, expression of P2X7 receptors, caspase-1 and NF-κB, release of IL-1β, calcium influx and PI uptake were reduced by 2354glu. SIRT1-LKB1-AMPK-SREBP1 axis-mediated lipid accumulation in HepG2 cells was reduced when they were cultured with conditioned media from LPS+ATP-activated THP-1 macrophages pretreated with 2354glu.Abbreviations: 2345glu, tetrahydroxystilbene glucoside, 2,3,5,4 0 -tetrahydroxy-stilbene-2-O-β-D-glucoside; AMPK, AMP-activated protein kinase; LKB1, liver kinase B1; NLRP3, nucleotidebinding oligomerization domain-like receptor protein 3; SIRT1, sirtuin 1; SREBP1, sterol regulatory element-binding protein 1; TLRs, toll like receptors.

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Critical role of tristetraprolin and AU‐rich element RNA‐binding protein 1 in the suppression of cancer cell growth by globular adiponectin

et al. 2018

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Adiponectin exhibits potent antitumor activities. Herein, we examined the molecular mechanisms underlying suppression of tumor growth by globular adiponectin ( gA crp). We demonstrated that gA crp suppressed B‐cell lymphoma 2 (Bcl‐2) expression, an anti‐apoptotic gene, by inducing its mRNA destabilization, which was accompanied with a decrease in cell viability and increased caspase‐3 activity in hepatic cancer cells. In addition, gA crp increased expression of tristetraprolin ( TTP ) and AU‐rich element RNA‐binding protein 1 ( AUF 1), which are mRNA stability regulatory proteins. Moreover, gA crp‐induced suppression of Bcl‐2 expression was abrogated by knockdown of TTP or AUF 1. These data indicate that gA crp induces apoptosis of hepatic cancer cells by TTP ‐ and AUF 1‐mediated Bcl‐2 mRNA destabilization, and further suggest that TTP and AUF 1 are novel targets mediating the antitumor activity of adiponectin.

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Adiponectin inhibits inflammatory cytokines production by Beclin‐1 phosphorylation and B‐cell lymphoma 2 mRNA destabilization: role for autophagy induction

Cited by 23 publications

References 67 publications

ZFP36L1 and AUF1 Induction Contribute to the Suppression of Inflammatory Mediators Expression by Globular Adiponectin via Autophagy Induction in Macrophages

ZFP36L1 and AUF1 Induction Contribute to the Suppression of Inflammatory Mediators Expression by Globular Adiponectin via Autophagy Induction in Macrophages

P2X7 receptor‐targeted regulation by tetrahydroxystilbene glucoside in alcoholic hepatosteatosis: A new strategy towards macrophage–hepatocyte crosstalk

Critical role of tristetraprolin and AU‐rich element RNA‐binding protein 1 in the suppression of cancer cell growth by globular adiponectin

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