scholarly journals Diet-Induced Obesity Mice Execute Pulmonary Cell Apoptosis via Death Receptor and ER-Stress Pathways after E. coli Infection

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Fengyuan Wang ◽  
Zhicai Zuo ◽  
Kejie Chen ◽  
Jing Fang ◽  
Hengmin Cui ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cell Apoptosis ◽  
High Fat Diet ◽  
Death Receptor ◽  
Apoptotic Pathway ◽  
E Coli ◽  
Diet Induced Obesity ◽  
Protein Expressions ◽  
Acute Pneumonia

Obesity has developed into a considerable health problem in the whole world. Escherichia coli (E. coli) can cause nosocomial pneumonia and induce cell apoptosis during injury and infection. Normal (lean) and diet-induced obesity mice (DIO, fed with high-fat diet) were chosen to perform nasal instillation with E. coli to establish a nonfatal acute pneumonia model. At 0 h, 12 h, 24 h, and 72 h postinfection, lung tissues were obtained to measure cell apoptosis. As shown in this study, both lean and DIO mice exhibited histopathological lesions of acute pneumonia and increased cell apoptosis in the lung infected with E. coli. Interestingly, the relative mRNA and protein expressions associated with either endoplasmic reticulum stress or death receptor apoptotic pathway were all dramatically increased in the DIO mice after infection, while only significant upregulation of death receptor apoptotic pathway in the lean mice at 72 h. These results indicated that the DIO mice executed excess cell apoptosis in the nonfatal acute pneumonia induced by E. coli infection through endoplasmic reticulum stress and death receptor apoptotic pathway.

scholarly journals Oleoylethanolamide Reduces Hepatic Oxidative Stress and Endoplasmic Reticulum Stress in High-Fat Diet-Fed Rats

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1289
Author(s):  
Anna Maria Giudetti ◽  
Daniele Vergara ◽  
Serena Longo ◽  
Marzia Friuli ◽  
Barbara Eramo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
High Fat Diet ◽  
Free Access ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Antioxidant Genes ◽  
Diet Induced Obesity ◽  
Hepatic Oxidative Stress

Long-term high-fat diet (HFD) consumption can cause weight gain and obesity, two conditions often associated with hepatic non-alcoholic fatty liver and oxidative stress. Oleoylethanolamide (OEA), a lipid compound produced by the intestine from oleic acid, has been associated with different beneficial effects in diet-induced obesity and hepatic steatosis. However, the role of OEA on hepatic oxidative stress has not been fully elucidated. In this study, we used a model of diet-induced obesity to study the possible antioxidant effect of OEA in the liver. In this model rats with free access to an HFD for 77 days developed obesity, steatosis, and hepatic oxidative stress, as compared to rats consuming a low-fat diet for the same period. Several parameters associated with oxidative stress were then measured after two weeks of OEA administration to diet-induced obese rats. We showed that OEA reduced, compared to HFD-fed rats, obesity, steatosis, and the plasma level of triacylglycerols and transaminases. Moreover, OEA decreased the amount of malondialdehyde and carbonylated proteins and restored the activity of antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, which decreased in the liver of HFD-fed rats. OEA had also an improving effect on parameters linked to endoplasmic reticulum stress, thus demonstrating a role in the homeostatic control of protein folding. Finally, we reported that OEA differently regulated the expression of two transcription factors involved in the control of lipid metabolism and antioxidant genes, namely nuclear factor erythroid-derived 2-related factor 1 (Nrf1) and Nrf2, thus suggesting, for the first time, new targets of the protective effect of OEA in the liver.

scholarly journals Delayed Pulmonary Apoptosis of Diet-Induced Obesity Mice following Escherichia coli Infection through the Mitochondrial Apoptotic Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Fengyuan Wang ◽  
Zhicai Zuo ◽  
Zhuangzhi Yang ◽  
Kejie Chen ◽  
Jing Fang ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Metabolic Diseases ◽  
Pulmonary Inflammation ◽  
Caspase 9 ◽  
Apoptotic Pathway ◽  
E Coli ◽  
Diet Induced Obesity ◽  
Protein Expressions ◽  
Pulmonary Cells ◽  
Escherichia Coli Infection

Escherichia coli (E. coli) is one of pathogens causing nosocomial pneumonia and could induce pulmonary excessive apoptosis. Although much has been learned about metabolic diseases induced by obesity, the information linking bacterial pneumonia to obesity is limited. Accordingly, we investigated the apoptosis of normal (lean) and diet-induced obesity (DIO, fed a high-fat diet) mice after nasal instillation with E. coli. Lung tissues were obtained at 0 (preinfection), 12, 24, and 72 h after infection, and acute pulmonary inflammation was observed at 12 h. Elevated cell apoptosis and percentage of pulmonary cells depolarized with collapse of the mitochondrial transmembrane potential (Δψm) occurred in response to bacterial infection. The relative mRNA and protein expressions of Bax, caspase-3, and caspase-9 increased, but Bcl-2 decreased in the lung. Interestingly, the apoptotic percentage and most of apoptosis-associated factors mentioned above peaked at 12 or 24 h in the lean-E. coli group, while at 24 or 72 h in the DIO-E. coli group. Taken together, these findings indicated that the E. coli pneumonia caused excessive pulmonary apoptosis through the mitochondria-mediated pathway, and the apoptosis was delayed in the DIO mice with E. coli pneumonia.

scholarly journals Ubiquitin-Activating Enzyme E1 Inhibition Caused Acute Leukemia Cell Apoptosis By Affecting CHOP Pathway

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2784-2784
Author(s):  
Ju Bai ◽  
Aili He ◽  
Jianli Wang ◽  
Yun Yang ◽  
Ying Shen ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cell Apoptosis ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Leukemia Cell ◽  
Death Receptor ◽  
Leukemia Cells ◽  
Bax Protein ◽  
Average Survival

Abstract Background: The ubiquitin proteinase system is involved in the pathogenesis of blood malignant tumors. Preliminary study of our group found that increased serum ubiquitin activase E1 (UBE1) fragment were in newly diagnosed and refractory & relapsed acute myeloid leukemia (AML), and its relative intensity was negatively correlated with AML's remission process and prognosis. The inhibition of UBE1 activity can promote AML cell apoptosis and may be related to the mechanism of endoplasmic reticulum stress. The current study is to clarify the role and mechanism of endoplasmic reticulation-derived transcription factor CHOP in apoptosis of leukemia cells induced by inhibiting ubiquitin activase E1 (UBE1) activity. Methods: UBE1-shRNA lentivirus carrier and CHOP-siRNA plasmid co-infected leukemia cells (U937, K562, NB4, THP-1). The protein expression of antiapoptosis molecules, endoplasmic reticulum stress protein and death receptors (Bcl-2, TRB3, ERO1α, DR5 and Bax) were detected by Western Blot. MTT and flow cytometry were used to detect cell proliferation inhibition and apoptosis. The model of leukemia cell bearing nude mouse was constructed. UBE1-shRNA and/or CHOP-siRNA were injected into the tumor. The tumor size, lifetime changes and tumor pathological changes were observed. Western Blot and RT-PCR were used to detect endoplasmic reticulum stress molecules and apoptosis molecules. Results: Infection of UBE1-shRNA significantly inhibited proliferation of leukemia cells (U937, K562, NB4, THP-1), while the inhibition of UBE1-shRNA and CHOP-siRNA co-transfected leukemia cells was decreased (p=0.032). The apoptosis rate in UBE1-shRNA leukemia cells was lower than that in UBE1-shRNA and CHOP-siRNA co-transfected leukemia cells (p=0.026). UBE1-shRNA can reduce the expression of apoptosis molecule Bcl-2 and increase the expression of TRB3, ERO1α, death receptor DR5, Bax protein. CHOP-siRNA can increase the expression of Bcl-2 in leukemia cells and reduce the expression of TRB3, ERO1α, death receptor DR5 and Bax protein. shRNA-UBE1 inhibited the leukemia cell xenograft, while siRNA-CHOP reversed the growth inhibition of shRNA-UBE1 on leukemia cell xenograft (p=0.002). A larger number of leukemia cells were degenerative necrosis in the UBE1-shRNA group comparing with the UBE1-shRNA and siRNA-CHOP co-transfected groups (p=0.023), and damaged membrane, different sizes, blurred outline, and nuclear pyknosis and karyorrhexis could be observed. The average survival time of mice with co-transfection of shRNA-UBE1 and siRNA-CHOP was shorter than the average survival time of mice with shRNA-UBE1 (p=0.016). Compared with the shRNA-UBE1 group, there was no difference in expression of endoplasmic reticulum stress molecules in co-transfection of UBE1-shRNA and siRNA-CHOP group, but TRB3, ERO1α, DR5, Bax expression were decreased, and Bcl-2 was increased (p<0.05). Conclusion: The inhibition of UBE1 activity can induce AML cell apoptosis by endoplasmic reticulum stress CHOP pathway. It will provide new clues for the treatment of acute myeloid leukemia. Disclosures: No relevant conflicts of interest to declare. Disclosures No relevant conflicts of interest to declare.

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