scholarly journals Cadmium affects autophagy in the human intestinal cells Caco-2 through ROS-mediated ERK activation

2021 ◽  
Author(s):  
Myriam Mireault ◽  
Yong Xiao ◽  
Benoît Barbeau ◽  
Catherine Jumarie
Keyword(s):  
Critical Role ◽  
Toxic Metal ◽  
Glucose Deprivation ◽  
Intestinal Cells ◽  
Autophagic Flux ◽  
Erk Activation ◽  
Cell Monolayers ◽  
Nutritional Conditions ◽  
Human Intestinal Cells

Abstract Cadmium is a toxic metal that enters the food chain. Following oral ingestion, the intestinal epithelium has the capacity to accumulate high levels of this metal. We have previously shown that Cd induces ERK1/2 activation in differentiated but not proliferative human enterocytic-like Caco-2 cells. As autophagy is a dynamic process that plays a critical role in intestinal mucosa, we aimed the present study 1) to investigate the role of p-ERK1/2 in constitutive autophagy in proliferative Caco-2 cells and 2) to investigate whether Cd-induced activation of ERK1/2 modifies autophagic activity in postconfluent Caco-2 cell monolayers. Western blot analyses of ERK1/2 and autophagic markers (LC3, SQSTM1), and cellular staining with acridine orange showed that ERK1/2 and autophagic activities both decreased with time in culture. GFP-LC3 fluorescence was also associated with proliferative cells and the presence of a constitutive ERK1/2-dependent autophagic flux was demonstrated in proliferative but not in postconfluent cells. In the latter condition, serum and glucose deprivation triggered autophagy via a transient phosphorylation of ERK1/2, whereas Cd-modified autophagy via a ROS-dependent sustained activation of ERK1/2. Basal autophagy flux in proliferative cells and Cd-induced increases in autophagic markers in postconfluent cells both involved p-ERK1/2. Whether Cd blocks autophagic flux in older cell cultures remains to be clarified but our data suggest dual effects. Our results prompt further studies investigating the consequences that Cd-induced ERK1/2 activation and the related effect on autophagy may have on the intestinal cells, which may accumulate and trap high levels of Cd under some nutritional conditions. Graphical abstract

Role of P-glycoprotein in the efflux of raltegravir from human intestinal cells and CD4+ T-cells as an interaction target for anti-HIV agents

2013 ◽  
Vol 439 (2) ◽  
pp. 221-227 ◽  
Author(s):  
Yumi Hashiguchi ◽  
Akinobu Hamada ◽  
Takashi Shinohara ◽  
Kiyoto Tsuchiya ◽  
Hirofumi Jono ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Intestinal Cells ◽  
P Glycoprotein ◽  
Anti Hiv Agents ◽  
Anti Hiv ◽  
Human Intestinal Cells

scholarly journals Protective role of microRNA-9-5p in oxygen glucose deprivation/reperfusion-induced injury in liver sinusoidal endothelial cell

2020 ◽  
Author(s):  
Yi Duan ◽  
Zhifeng Gao ◽  
Xiaoyu Wang ◽  
Yuanyuan Meng ◽  
Huan Zhang
Keyword(s):  
Inflammatory Response ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Glucose Deprivation ◽  
Protective Role ◽  
Liver Sinusoidal Endothelial Cell ◽  
Liver Sinusoidal Endothelial Cells ◽  
Hepatic Ischemia

Abstract Background: Maintenance of the function and survival of liver sinusoidal endothelial cells (LSECs) play a crucial role in hepatic ischemia/reperfusion (I/R) injury, a major cause of liver impairment during surgical treatment. Emerging evidence indicate a critical role of microRNAs in I/R injury. This study aims to investigate whether miR-9-5p exert a protective effect on LSECs in vitro .Methods: We transfected LSECs with miR-9-5p mimic or mimic NC. LSECs were treated with oxygen and glucose deprivation (OGD, 5% CO2 and 95% N2), followed by glucose-free DMEM medium for 6 h, and high-glucose (HG, 30 mmol/L glucose) DMEM medium for 12 h. The biological role of miR-9-5p in I/R-induced LSEC injury was determined. Results: In the in vitro model of OGD/HG injury in LSECs, the expression levels of miR-9-5p were significantly downregulated and those of CXC chemokine receptor-4 (CXCR4) upregulated. LSEC I/R injury led to deteriorated cell death, enhanced oxidative stress and excessive inflammatory response. Mechanistically, we showed that miR-9-5p overexpression significantly upregulated both mRNA and protein levels of CXCR4, followed by rescue of LSECs, ameliorated inflammatory response, and deactivation of pro-apoptotic signaling pathways.Conclusion: miR-9-5p promotes LSEC survival and inhibits apoptosis and inflammatory response in LSECs following OGD/HG injury via downregulation of CXCR4.

scholarly journals Critical Role of H2O2 Generated by NOX4 during Cellular Response under Glucose Deprivation

PLoS ONE ◽  
2013 ◽  
Vol 8 (3) ◽  
pp. e56628 ◽  
Author(s):  
Satoshi Owada ◽  
Yuko Shimoda ◽  
Katsuya Tsuchihara ◽  
Hiroyasu Esumi
Keyword(s):  
Cellular Response ◽  
Critical Role ◽  
Glucose Deprivation

scholarly journals microRNA-9-5p protects liver sinusoidal endothelial cell against oxygen glucose deprivation/reperfusion injury

2021 ◽  
Vol 16 (1) ◽  
pp. 375-383
Author(s):  
Yi Duan ◽  
Yuanyuan Meng ◽  
Zhifeng Gao ◽  
Xiaoyu Wang ◽  
Huan Zhang
Keyword(s):  
Inflammatory Response ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Glucose Deprivation ◽  
Liver Sinusoidal Endothelial Cell ◽  
Liver Sinusoidal Endothelial Cells ◽  
Hepatic Ischemia ◽  
Protein Levels

Abstract Background Maintenance of the function and survival of liver sinusoidal endothelial cells (LSECs) play a crucial role in hepatic ischemia/reperfusion (I/R) injury, a major cause of liver impairment during the surgical treatment. Emerging evidence indicates a critical role of microRNAs in I/R injury. This study aims to investigate whether miR-9-5p exerts a protective effect on LSECs. Methods We transfected LSECs with miR-9-5p mimic or mimic NC. LSECs were treated with oxygen and glucose deprivation (OGD, 5% CO2, and 95% N2), followed by glucose-free Dulbecco’s modified Eagle’s medium (DMEM) medium for 6 h and high glucose (HG, 30 mmol/L glucose) DMEM medium for 12 h. The biological role of miR-9-5p in I/R-induced LSEC injury was determined. Results In the in vitro model of OGD/HG injury in LSECs, the expression levels of miR-9-5p were significantly downregulated, and those of CXC chemokine receptor-4 (CXCR4) upregulated. LSEC I/R injury led to deteriorated cell death, enhanced oxidative stress, and excessive inflammatory response. Mechanistically, we showed that miR-9-5p overexpression significantly downregulated both mRNA and protein levels of CXCR4, followed by the rescue of LSECs, ameliorated inflammatory response, and deactivation of pro-apoptotic signaling pathways. Conclusions miR-9-5p promotes LSEC survival and inhibits apoptosis and inflammatory response in LSECs following OGD/HG injury via downregulation of CXCR4.

scholarly journals Maintaining proton homeostasis is an essential role of glucose metabolism in cell survival

2016 ◽  
Author(s):  
Yanfen Cui ◽  
Yuanyuan Wang ◽  
Pan Xing ◽  
Li Qiu ◽  
Miao Liu ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Cell Survival ◽  
Aerobic Glycolysis ◽  
Critical Role ◽  
Glucose Deprivation ◽  
Proliferating Cells ◽  
Cellular Apoptosis ◽  
Induced Apoptosis ◽  
Apoptosis And Necrosis

AbstractAerobic glycolysis, termed “the Warburg Effect”, supports cell proliferation, and glucose deprivation directly elicits necrosis or shifts stimuli-induced apoptosis to necrosis. However, how glucose metabolism regulates cell survival or death choice remains largely unclear. Here we use our recently developed method to monitor in real-time cellular apoptosis and necrosis, and uncover a metabolic homeostasis linked to cell death control. We show that glucose metabolism is the major source to maintain both intracellular and extracellular proton homeostasis. Glucose deficiency leads to lack of proton provision, which provokes a compensatory lysosomal proton efflux and resultant increased lysosomal pH. This lysosomal alkalinization can trigger necrosis. Furthermore, artificial proton supplement enables cells to survive glucose deprivation. Taken together, our results reveal a critical role of glucose metabolism in maintaining cellular microenvironment, and provide a better understanding of the essential requirement of aerobic glycolysis for proliferating cells whose active anabolism consumes a great many protons.

scholarly journals α-Linolenic acid but not linolenic acid protects against hypertension: critical role of SIRT3 and autophagic flux

2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Guohua Li ◽  
Xinpei Wang ◽  
Hongyan Yang ◽  
Pengfei Zhang ◽  
Fangqin Wu ◽  
...  
Keyword(s):  
Linolenic Acid ◽  
Critical Role ◽  
Autophagic Flux

Endothelial cell monolayers as a tool for studying microvascular pathophysiology

1997 ◽  
Vol 273 (6) ◽  
pp. G1189-G1199 ◽  
Author(s):  
Peter R. Kvietys ◽  
D. Neil Granger
Keyword(s):  
Endothelial Cell ◽  
In Vitro Model ◽  
Cultured Cells ◽  
Critical Role ◽  
In Vitro Models ◽  
Cell Monolayers ◽  
Biological Responses ◽  
Vitro Model

Endothelial cells contribute to a variety of biological responses that facilitate organ function. This critical role of the endothelial cell has resulted in the development of different in vitro models that utilize monolayers of cultured cells to simulate conditions that exist in the intact animal. This review focuses on endothelial cell monolayers as a model system for research on certain pathophysiological conditions affecting the gastrointestinal tract. The advantages and limitations of endothelial cell monolayers are addressed, along with evolving technologies and strategies that hold promise for extending the utility of this in vitro model for studies of gastrointestinal function and disease.

scholarly journals Carbon monoxide released by CORM-A1 prevents yeast cell death via autophagy stimulation

2019 ◽  
Vol 19 (5) ◽  
Author(s):  
Cláudia Figueiredo-Pereira ◽  
Regina Menezes ◽  
Sofia Ferreira ◽  
Cláudia N Santos ◽  
Helena L A Vieira
Keyword(s):  
Oxidative Stress ◽  
Carbon Monoxide ◽  
Cell Death ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Primary Cultures ◽  
Autophagic Flux ◽  
Dependent Manner ◽  
Yeast Saccharomyces Cerevisiae

ABSTRACT Autophagy is an autodigestive process, promoting cytoprotection by the elimination of dysfunctional organelles, misfolded proteins and toxic aggregates. Carbon monoxide (CO) is an endogenous gasotransmitter that under low concentrations prevents cell death and inflammation. For the first time, the role of autophagy in CO-mediated cytoprotection against oxidative stress was evaluated in the model yeast Saccharomyces cerevisiae. The boron-based CO-releasing molecule, CORM-A1, was used to deliver CO. CORM-A1 partially prevented oxidative stress-induced cell death in yeast. Likewise, CORM-A1 activated autophagy under basal physiological conditions, which were assessed by autophagic flux and the expression of mCherry-Atg8 or GFP-Atg8. Inhibition of autophagy by knocking out key autophagic genes in yeast (ATG8 or ATG11) blocked CORM-A1 cytoprotective effect, indicating the critical role of autophagy in CO-induced cytoprotection. The CO-mediated cytoprotection via autophagy induction observed in yeast was validated in primary cultures of astrocytes, a well-characterized model for CO's cytoprotective functions. As in yeast, CORM-A1 prevented oxidative stress-induced cell death in an autophagy-dependent manner in astrocytes. Overall, our data support the cytoprotective action of CO against oxidative stress. CO promotes cytoprotection in yeast via autophagy, opening new possibilities for the study of molecular mechanisms of CO's biological functions using this powerful eukaryotic model.

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