Down-regulation of BNIP3 by olomoucine, a CDK inhibitor, reduces LPS- and NO-induced cell death in BV2 microglial cells

Tsou, Yu Chi; Wang, Hsiao Hsien; Hsieh, Chii Cheng; Sun, Kien-Wen; Sun, Guang; Jhou, Ren Shiang; Lin, Tz I.; Lu, Shou Yun; Liu, Huan Yun; Tang, Shanshan

doi:10.1016/j.neulet.2016.06.040

Cited by 9 publications

(4 citation statements)

References 24 publications

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“…To specify the involvement of BNIP3, the effect of olomoucine, a transcriptional inhibitor of BNIP3 ( 69 ) on TLR7/8-induced mitophagy in CD1c + mDC was examined. Olomoucine significantly reduced steady state BNIP3 (Figure 5D ) and the pRNA-induced increase of BNIP3 in CD1c + mDC (Figure 5D ).…”

Section: Resultsmentioning

confidence: 99%

Human Dendritic Cell Subsets Undergo Distinct Metabolic Reprogramming for Immune Response

et al. 2018

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Toll-like receptor (TLR) agonists induce metabolic reprogramming, which is required for immune activation. We have investigated mechanisms that regulate metabolic adaptation upon TLR-stimulation in human blood DC subsets, CD1c+ myeloid DCs (mDCs) and plasmacytoid DCs (pDCs). We show that TLR-stimulation changes expression of genes regulating oxidative phosphorylation (OXPHOS) and glutamine metabolism in pDC. TLR-stimulation increases mitochondrial content and intracellular glutamine in an autophagy-dependent manner in pDC. TLR-induced glutaminolysis fuels OXPHOS in pDCs. Notably, inhibition of glutaminolysis and OXPHOS prevents pDC activation. Conversely, TLR-stimulation reduces mitochondrial content, OXPHOS activity and induces glycolysis in CD1c+ mDC. Inhibition of mitochondrial fragmentation or promotion of mitochondrial fusion impairs TLR-stimulation induced glycolysis and activation of CD1c+ mDCs. TLR-stimulation triggers BNIP3-dependent mitophagy, which regulates transcriptional activity of AMPKα1. BNIP3-dependent mitophagy is required for induction of glycolysis and activation of CD1c+ mDCs. Our findings reveal that TLR stimulation differentially regulates mitochondrial dynamics in distinct human DC subsets, which contributes to their activation.

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Section: Resultsmentioning

confidence: 99%

Human Dendritic Cell Subsets Undergo Distinct Metabolic Reprogramming for Immune Response

et al. 2018

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“…In a previous study, olomoucine was shown to inhibit lipopolysaccharide‐induced nitric oxide generation and expression of pro‐inflammatory cytokines in microglial cells by reducing the expression of BNIP3 (Tsou et al . 2016). In the present study, olomoucine significantly reduced BNIP3 protein expression by ∼50% with a corresponding inhibition of ATP release.…”

Section: Discussionmentioning

confidence: 99%

Fungal allergen‐induced IL‐33 secretion involves cholesterol‐dependent, VDAC‐1‐mediated ATP release from the airway epithelium

Srisomboon

Squillace

Maniak

et al. 2020

The Journal of Physiology

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Alternaria aeroallergens induce the release of ATP from human bronchial epithelial (HBE) cells by activating a conductive pathway involving voltage-dependent anion channel-1 (VDAC-1) and by exocytosis of ATP localized within membrane vesicles. r Inhibition of VDAC-1 blocked Alternaria-evoked Ca 2+ uptake across the plasma membrane of HBE cells and interleukin (IL)-33 release into the extracellular media. r Reducing cholesterol content with a cholesterol scavenger (β-methylcyclodextrin) or statin compound (simvastatin) blocked ATP and IL-33 release by lowering the expression of VDAC-1 in the plasma membrane. r Pretreatment with simvastatin for 24 h also inhibited the increase in tight junction macromolecule permeability that occurs following Alternaria exposure. r These results establish a novel role for VDAC-1 as a mechanism underlying ATP release induced by fungal allergens and suggests a possible therapeutic use for cholesterol lowering compounds in reducing Alternaria-stimulated allergic inflammation.

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“…Research showes that A6, as a naturally selective inhibitor of cyclin‐dependent kinases (CDKs)‐1/2, participates in the progression from G1 to S phase and from G2 to M phase in HuH‐7 or Hela cell, respectively (38). Furthermore, inhibitors of CDKs could clear potentially injurious inflammatory cells and enhance the resolution of inflammation by both limiting cell proliferation and promoting cell apoptosis (43, 44). But in our cell viability assay, we found that A6 had no effect on cell proliferation by CCK8 in normal cells NCM460 and 16HBE.…”

Section: Discussionmentioning

confidence: 99%

Butyrolactone‐I, an efficient α‐glucosidase inhibitor, improves type 2 diabetes with potent TNF‐α–lowering properties through modulating gut microbiota in db/db mice

Liu

Zhu

et al. 2019

The FASEB Journal

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The aim of this study was to evaluate the effects of butyrolactone‐I (A6) on type 2 diabetes (T2D) in db/db mice because A6 was found to inhibit α‐glucosidase activities and TNF‐α release, which were associated with improving T2D. Male db/db mice were divided into 6 groups and given an equivalent volume of olive oil, acarbose, or different doses of A6 for 4 wk (n = 8/group). In this study, 11 butenolide derivatives were screened for their α‐glucosidase and TNF‐α suppressive activity in vitro. A6, an efficient α‐glucosidase inhibitor, exerts hypoglycemic and multiple activities in reducing weight, improving glucose tolerance and insulin resistance, increasing short‐chain fatty acid (SCFA) levels, activating SCFA‐induced increases in glucagon‐like peptide 1 and peroxisome proliferator‐activated receptor‐γ expression, enhancing intestinal mucosal barrier function and mitigating endoxemia in db/db mice. These effects may result from mediation of gut microbiota by A6. Meanwhile, A6, with potent TNF‐α–lowering properties, was demonstrated to have multiple salutary effects with excellent structural stability and long‐term safety in vivo. A6, an effective α‐glucosidase inhibitor with high security and stability, exerted potent antidiabetic effects in vivo. Furthermore, the modulation of gut microbiota of A6 was demonstrated to be one of the mechanisms contributing to anti‐inflammation properties and improving endoxemia. Our work confirms that the compound A6 is a prospective drug candidate for T2D.—Wu, W., Liu, L., Zhu, H., Sun, Y., Wu, Y., Liao, H., Gui, Y., Li, L., Liu, L., Sun, F., Lin, H. Butyrolactone‐I, an efficient α‐glucosidase inhibitor, improves type 2 diabetes with potent TNF‐α–lowering properties through modulating gut microbiota in db/db mice. FASEB J. 33, 12616–12629 (2019). http://www.fasebj.org

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Down-regulation of BNIP3 by olomoucine, a CDK inhibitor, reduces LPS- and NO-induced cell death in BV2 microglial cells

Cited by 9 publications

References 24 publications

Human Dendritic Cell Subsets Undergo Distinct Metabolic Reprogramming for Immune Response

Human Dendritic Cell Subsets Undergo Distinct Metabolic Reprogramming for Immune Response

Fungal allergen‐induced IL‐33 secretion involves cholesterol‐dependent, VDAC‐1‐mediated ATP release from the airway epithelium

Butyrolactone‐I, an efficient α‐glucosidase inhibitor, improves type 2 diabetes with potent TNF‐α–lowering properties through modulating gut microbiota in db/db mice

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