BDE-209 induces autophagy and apoptosis via IRE1α/Akt/mTOR signaling pathway in human umbilical vein endothelial cells

Hou, Yun; Fu, JiaRong; Sun, Shitian; Jin, Young–Joo; Wang, Xifeng; Zhang, Lianshuang

doi:10.1016/j.envpol.2019.07.030

Cited by 34 publications

(13 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Significant level of ROS was detected in HUVECs from low to high concentrations of TCPP, confirming its ability to act as an oxidative stressor in the vascular system. The ROS data are in close agreement with a previous study validating ROS production in HUVECs upon exposure with an FR (BDE‐209) (Hou et al, 2019). The destabilization of lysosomes also confirmed by our NRU assay data has been manifested as an initial event in the mitochondrial injury (Saquib et al, 2016).…”

Section: Discussionsupporting

confidence: 91%

“…OPFRs and BFRs have been linked with the enhancement of intracellular ROS, which participate to instigate oxidative stress in cells (Al‐Salem et al, 2019; Hou et al, 2019). Excessive accumulation of ROS in cells has been categorized as one of the key factors to induce DNA damage, mitochondrial dysfunction, and apoptosis (Al‐Salem et al, 2019; Saquib et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…HUVECs exposed to OPFRs (TDCPP) for 24 h significantly affected the vascular endothelial growth factor (VEGF) signaling pathway and declined the cell survival (Zhong et al, 2019). Also, BDE‐209 induced the autophagic cell death in HUVECs via RE1α/AKT/mTOR signaling pathway, endoplasmic reticulum (ER), and oxidative stresses by reactive oxygen species (ROS) production (Hou et al, 2019). Regardless of the fact, till date, TCPP has not been studied for its vascular toxicity.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Organophosphorus flame‐retardant tris(1‐chloro‐2‐propyl)phosphate is genotoxic and apoptotic inducer in human umbilical vein endothelial cells

Saquib

Siddiqui

Al‐Khedhairy

2021

J of Applied Toxicology

View full text Add to dashboard Cite

Tris(1‐chloro‐2‐propyl)phosphate (TCPP) is a chlorinated organophosphorus flame retardant (OPFR) widely used in consumer goods after the phaseout of brominated flame retardants (BFRs). TCPP can percolate into the indoor and outdoor dusts, leading to its detection in the human body fluids (urine, breast milk) and placenta. However, TCPP has not been studied so far for its toxicity in the human vascular system. Hence, we have used human umbilical vein endothelial cells (HUVECs) and exposed them to TCPP ranging from low to high (5–400 μM) concentrations for 24 h. Cytotoxicity analysis by MTT and NRU assays exhibited 15.27% and 20.56%, 21.67%, and 48.67% survival decline of cells only at 200 and 400 μM. Comet assay data showed DNA damage from 50 to 400 μM with Olive tail moment (OTM) values between 1.03 and 35.59, respectively. TCPP‐exposed HUVECs exhibited 1.09 and 1.39‐fold greater intracellular reactive oxygen species (ROS) at 25 and 400 μM, indicating oxidative stress. HUVEC mitochondrial membrane potential (ΔΨm) measurements showed 1.16 and 1.48‐fold higher fluorescence of Rh123 dye at 25 and 400 μM, confirming mitochondrial dysfunction. Flow cytometric data demonstrated 5.1%–58.8% cells in SubG1 apoptotic phase at 5 and 400 μM TCPP. Our novel data revealed that TCPP is a genotoxic and apoptotic inducer, which may trigger alike responses in human vascular system. Overall, detailed in vivo studies are warranted on the transcriptional and translations effects of TCPP.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Organophosphorus flame‐retardant tris(1‐chloro‐2‐propyl)phosphate is genotoxic and apoptotic inducer in human umbilical vein endothelial cells

Saquib

Siddiqui

Al‐Khedhairy

2021

J of Applied Toxicology

View full text Add to dashboard Cite

show abstract

“…We next attempted to gain insights into the molecular mechanisms by which BCAT1 regulates autophagy under hypoxia. Although many studies have proven the relationship between autophagy and ERs 33 – 35 , these reports were mainly focused on the endothelium 36 . The role of BCAT1 in the smooth muscle layer has not been explored.…”

Section: Resultsmentioning

confidence: 99%

BCAT1 binds the RNA-binding protein ZNF423 to activate autophagy via the IRE1-XBP-1-RIDD axis in hypoxic PASMCs

Wei

Zhang

et al. 2020

Cell Death Dis

View full text Add to dashboard Cite

Abnormal functional changes in pulmonary artery smooth muscle cells are the main causes of many lung diseases. Among, autophagy plays a crucial role. However, the specific molecular regulatory mechanism of autophagy in PASMCs remains unclear. Here, we first demonstrate that BCAT1 played a key role in the autophagy of hypoxic PASMCs and hypoxic model rats. BCAT1-induced activation and accumulation of the autophagy signaling proteins BECN1 and Atg5 by the endoplasmic reticulum (ER) stress pathway. Interestingly, we discovered that BCAT1 bound IRE1 on the ER to activate expression of its downstream pathway XBP-1-RIDD axis to activate autophagy. More importantly, we identified an RNA-binding protein, zinc finger protein 423, which promoted autophagy by binding adenylate/uridylate (AU)-rich elements in the BCAT1 mRNA 3′-untranslated region. Overall, our results identify BCAT1 as a potential therapeutic target for the clinical treatment of lung diseases and reveal a novel posttranscriptional regulatory mechanism and signaling pathway in hypoxia-induced PASMC autophagy.

show abstract

“…ROS production due to oxidative stress was detected using the fluorescent probe 2,7-DCFH-DA 36 . During oxidative stress, 2,7-DCFH-DA can be oxidised by ROS to dichlorofluorescein (DCF), which can be detected fluorescently by FACS ( Figure 2(A) ).…”

Section: Resultsmentioning

confidence: 99%

Potential anti-neuroinflammatory NF-кB inhibitors based on 3,4-dihydronaphthalen-1(2H)-one derivatives

Sun

Zhou

Liu

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

Nuclear factor kappa B (NF-rB) inhibition represents a new therapeutic strategy for the treatment of neuroinflammatory diseases. In this study, a series of 3,4-dihydronaphthalen-1(2H)-one (DHN; 6a-n, 7a-c) derivatives were synthesised and characterised by NMR and HRMS. We assessed the toxicity and anti-neuroinflammatory properties of these compounds and found that 6m showed the greatest anti-neuroinflammatory properties, with relatively low toxicity. Specifically, 6m significantly reduced reactive oxygen species production, down-regulated the expression of NOD-like receptor pyrin domain-containing protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1 and prevented lipopolysaccharide-stimulated BV2 microglia cells polarisation towards an M1 phenotype. Furthermore, 6m significantly decreased IjBa and NF-rB p65 phosphorylation, thus inhibiting the NF-rB signalling pathway. This suggests that 6m may be explored as a functional anti-neuroinflammatory agent for the treatment of inflammatory diseases in the central nervous system, such as multiple sclerosis, traumatic brain injury, stroke and spinal cord injury.

show abstract

BDE-209 induces autophagy and apoptosis via IRE1α/Akt/mTOR signaling pathway in human umbilical vein endothelial cells

Cited by 34 publications

References 38 publications

Organophosphorus flame‐retardant tris(1‐chloro‐2‐propyl)phosphate is genotoxic and apoptotic inducer in human umbilical vein endothelial cells

Organophosphorus flame‐retardant tris(1‐chloro‐2‐propyl)phosphate is genotoxic and apoptotic inducer in human umbilical vein endothelial cells

BCAT1 binds the RNA-binding protein ZNF423 to activate autophagy via the IRE1-XBP-1-RIDD axis in hypoxic PASMCs

Potential anti-neuroinflammatory NF-кB inhibitors based on 3,4-dihydronaphthalen-1(2H)-one derivatives

Contact Info

Product

Resources

About