The effect of nicotine and dextrose on endoplasmic reticulum stress in human coronary artery endothelial cells

Gonzales, Krista; Feng, Victoria; Bikkina, Priyanka; Landicho, Marie Angelica; Haas, Michael J.; Mooradian, Arshag D.

doi:10.1093/toxres/tfab012

Cited by 8 publications

(4 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Apo A-I levels were calculated using Microsoft Excel and normalized to total protein measured with the bicinchoninic acid assay (Smith et al, 1985). The details of the Western blot methods were described previously (Gonzales et al, 2021).…”

Section: Apo A-i Enzyme Immune Assay (Eia) and Western Blot Analysismentioning

confidence: 99%

Insulin mimetic effect of D‐allulose on apolipoprotein A‐I gene

Haas

Parekh

Kalidas

et al. 2022

Journal of Food Biochemistry

View full text Add to dashboard Cite

Several nutrients modulate the transcriptional activity of the apolipoprotein A-I (apo A-I) gene. To determine the influence of rare sugars on apo A-I expression in hepatic (HepG2) and intestinal derived (Caco-2) cell lines, apo A-I, albumin, and SP1 were quantified with enzyme immunoassay and Western blots while mRNA levels were quantified with real-time polymerase chain reaction. The promoter activity was measured using transient transfection assays with plasmids containing various segments and mutations in the promoter. D-allulose and D-tagatose, increased apo A-I concentration in culture media while D-sorbose and D-allose did not have any measurable effects. D-allulose did not increase apo A-I levels in Caco-2 cells. These changes paralleled the increased mRNA levels and promoter activity. D-allulose-response was mapped at the insulin response core element (IRCE). Mutation of the IRCE decreased the ability of D-allulose and insulin to activate the promoter. Treatment of HepG2 cells, but not Caco-2 cells, with D-alluose and insulin increased SP1 expression relative to control cells. D-allulose augmented the expression and IRCE binding of SP1, an essential transcription factor for the insulin on apo A-I promoter activity. D-allulose can modulate some insulin-responsive genes and may have anti-atherogenic properties, in part due to increasing apo A-I production. Practical applicationsCoronary artery disease (CAD) is the number one cause of mortality in industrialized countries. A risk factor associated with CAD is low high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apo A-I) concentrations in plasma. Thus, novel therapeutic agents or nutrients that upregulate apo A-I production should be identified. D-allulose and D-tagatose are used as sweeteners and may have favorable effects on insulin resistance and diabetes. This study shows that D-allulose and D-tagatose increases apo A-I production through increased transcription factor SP1-binding to insulin response element of the promoter. These sweeteners modulate some insulin responsive genes, increase the production of apo-A-I, and therefore may have antiatherogenic properties.

show abstract

Section: Apo A-i Enzyme Immune Assay (Eia) and Western Blot Analysismentioning

confidence: 99%

Insulin mimetic effect of D‐allulose on apolipoprotein A‐I gene

Haas

Parekh

Kalidas

et al. 2022

Journal of Food Biochemistry

View full text Add to dashboard Cite

show abstract

“…As previously reported, the concentration of nicotine and cotinine was more than 100 ng/mL in the plasma of mice after two weeks of CS exposure 3 . Besides, Krista et al 4 revealed that nicotine exposure significantly increased endothelial apoptosis. Previously, we have found that the apoptosis of pulmonary microvascular endothelial cells (PMVECs) was increased in COPD patients and emphysema animal models exposed to cigarette smoke extract (CSE) 5 .…”

Section: Introductionmentioning

confidence: 99%

LRG1 promotes the apoptosis of pulmonary microvascular endothelial cells through KLK10 in chronic obstructive pulmonary disease

Cheng,

Song,

Zhou

et al. 2024

Tob. Induc. Dis.

View full text Add to dashboard Cite

INTRODUCTION Cigarette smoking is one of the most important causes of COPD and could induce the apoptosis of pulmonary microvascular endothelial cells (PMVECs). The conditional knockout of LRG1 from endothelial cells reduced emphysema in mice. However, the mechanism of the deletion of LRG1 from endothelial cells rescued by cigarette smoke (CS) induced emphysema remains unclear. This research aimed to demonstrate whether LRG1 promotes the apoptosis of PMVECs through KLK10 in COPD. METHODS Nineteen patients were divided into three groups: control non-COPD (n=7), smoker non-COPD (n=7), and COPD (n=5). The emphysema mouse model defined as the CS exposure group was induced by CS exposure plus cigarette smoke extract (CSE) intraperitoneal injection for 28 days. Primary PMVECs were isolated from the mouse by magnetic bead sorting method via CD31-Dynabeads. Apoptosis was detected by western blot and flow cytometry. RESULTS LRG1 was increased in lung tissue of COPD patients and CS exposure mice, and CSE-induced PMVECs apoptosis model. KLK10 was over-expressed in lung tissue of COPD patients and CS exposure mice, and CSE-induced PMVECs apoptosis model. LRG1 promoted apoptosis in PMVECs. LRG1 knockdown reversed CSE-induced apoptosis in PMVECs. The mRNA and protein expression of KLK10 were increased after over-expressed LRG1 in PMVECs isolated from mice. Similarly, both the mRNA and protein levels of KLK10 were decreased after LRG1 knockdown in PMVECs. The result of co-immunoprecipitation revealed a protein-protein interaction between LRG1 and KLK10 in PMVECs. KLK10 promoted apoptosis via the down-regulation of Bcl-2/Bax in PMVECs. KLK10 knockdown could reverse CSE-induced apoptosis in PMVECs. CONCLUSIONS LRG1 promotes apoptosis via up-regulation of KLK10 in PMVECs isolated from mice. KLK10 promotes apoptosis via the down-regulation of Bcl-2/ Bax in PMVECs. There was a direct protein-protein interaction between LRG1 and KLK10 in PMVECs. Our novel findings provide insights into the understanding of LRG1/KLK10 function as a potential molecule in COPD.

show abstract

“…Nicotine can increase malignancy through EMT in lung cancer ( Dasgupta et al, 2009 ; Pillai et al, 2015 ; Zhang et al, 2016 ; Du et al, 2018 ). Nicotine can directly induce ER stress response ( Pelissier-Rota et al, 2015 ; Barra et al, 2017 ; Gonzales et al, 2021 ; Jiang et al, 2021 ). In our previous study, we confirmed that nicotine concentration and time dependently increased the expression of ER stress associated apoptosis marker in human bronchial epithelial cells ( Lin et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Hydrogen Sulfide Inhibits Bronchial Epithelial Cell Epithelial Mesenchymal Transition Through Regulating Endoplasm Reticulum Stress

Lin

Liao

Zhang

et al. 2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

Epithelial mesenchymal transition (EMT) is a contributing factor in remodeling events of chronic obstructive pulmonary disease (COPD). Hydrogen sulfide (H2S) has been implicated in the pathogenesis of COPD, but the effect of H2S in regulating EMT and the underlying mechanisms is not clear. In this study, we assessed endoplasmic reticulum (ER) stress markers, EMT markers and associated signal molecules in rat lungs, bronchial epithelial cells, and human peripheral lung tissues to investigate the effect of H2S in regulating EMT and the underlying mechanisms. We found that EMT and ER stress occurred in lung epithelial cells, especially in the bronchial epithelial cells of smokers and COPD patients. In cigarette smoke (CS)-exposed rats, intraperitoneal injection of NaHS significantly alleviated CS-induced lung tissue damage, small airway fibrosis, ER stress, and EMT, while intraperitoneal injection of propargylglycine (cystathionine-gamma-lyase inhibitor) aggravated these effects induced by CS. In the nicotine-exposed 16HBE cells, an appropriate concentration of H2S donor not only inhibited nicotine-induced ER stress, but also inhibited nicotine-induced enhancement of cell migration ability and EMT. ER stress nonspecific inhibitors taurine and 4-phenyl butyric acid also inhibited nicotine-induced enhancement of cell migration ability and EMT. Both H2S and inositol-requiring enzyme 1 (IRE1) activation inhibitor 4μ8C inhibited nicotine-induced activation of IRE1, Smad2/3 and EMT. These results suggest that H2S inhibits CS- or nicotine-induced ER stress and EMT in bronchial epithelial cells and alleviates CS-induced lung tissue damage and small airway fibrosis. The IRE1 signal pathway and Smad2/3 may be responsible for the inhibitory effect of H2S.

show abstract

The effect of nicotine and dextrose on endoplasmic reticulum stress in human coronary artery endothelial cells

Cited by 8 publications

References 13 publications

Insulin mimetic effect of D‐allulose on apolipoprotein A‐I gene

Insulin mimetic effect of D‐allulose on apolipoprotein A‐I gene

LRG1 promotes the apoptosis of pulmonary microvascular endothelial cells through KLK10 in chronic obstructive pulmonary disease

Hydrogen Sulfide Inhibits Bronchial Epithelial Cell Epithelial Mesenchymal Transition Through Regulating Endoplasm Reticulum Stress

Contact Info

Product

Resources

About