scholarly journals PGC1α Promotes Cisplatin Resistance in Ovarian Cancer by Regulating the HSP70/HK2/VDAC1 Signaling Pathway

2021 ◽  
Vol 22 (5) ◽  
pp. 2537
Author(s):  
Yanqing Li ◽  
Jinsong Kang ◽  
Jiaying Fu ◽  
Haoge Luo ◽  
Yanan Liu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Signaling Pathway ◽  
Protein Transport ◽  
Cisplatin Resistance ◽  
Anion Channel ◽  
Underlying Mechanism ◽  
Peroxisome Proliferator ◽  
Voltage Dependent Anion Channel ◽  
Peroxisome Proliferator Activated Receptor ◽  
Resistant Cells

Mitochondrial apoptosis is one of the main mechanisms for cancer cells to overcome chemoresistance. Hexokinase 2 (HK2) can resist cancer cell apoptosis by expressing on mitochondria and binding to voltage-dependent anion channel 1 (VDAC1). We previously reported that peroxisome proliferator-activated receptor coactivator 1 α (PGC1α) is highly expressed in ovarian cancer cisplatin-resistant cells. However, the underlying mechanism remains unclear. Therefore, we evaluated the interaction between PGC1α and HK2 in ovarian cancer cisplatin-resistant cells. We found that the knockdown of PGC1α promotes the apoptosis of ovarian cancer cisplatin-resistant cells and increases their sensitivity to cisplatin. In addition, we found that the knockdown of PGC1α affects the mitochondrial membrane potential and the binding of HK2 and VDAC1. As the heat shock protein 70 (HSP70) family can help protein transport, we detected it and found that PGC1α can promote HSP70 gene transcription. Furthermore, HSP70 can promote an increase of HK2 expression on mitochondria and an increase of binding to VDAC1. Based on these results, PGC1α may reduce apoptosis through the HSP70/HK2/VDAC1 signaling pathway, thus promoting cisplatin resistance of ovarian cancer. These findings provide strong theoretical support for PGC1α as a potential therapeutic target of cisplatin resistance in ovarian cancer.

Gabapentin Reduces Alcohol Intake in Rats by Regulating NF-κB Signaling Pathway Via PPAR γ

2021 ◽  
Author(s):  
Jing Li ◽  
Kewei Xu ◽  
Hao Ding ◽  
Qiaozhen Xi
Keyword(s):  
Locomotor Activity ◽  
Signaling Pathway ◽  
Specific Inhibitor ◽  
Underlying Mechanism ◽  
Ethanol Consumption ◽  
Diglycidyl Ether ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Tnf Α

Abstract Aims Increasing preclinical and clinical reports have demonstrated the efficacy of gabapentin (GBP) in treating alcohol use disorder (AUD). However, the mechanism of the effects of GBP in AUD is largely unknown. Herein, we sought to investigate the effect of GBP in a rat model of AUD and explore the underlying mechanism. Methods The intermittent access to 20% ethanol in a 2-bottle choice (IA2BC) procedure was exploited to induce high voluntary ethanol consumption in rats. The rats were treated daily for 20 days with different doses of GBP, simultaneously recording ethanol/water intake. The locomotor activity and grooming behavior of rats were also tested to evaluate the potential effects of GBP on confounding motor in rats. The levels of IL-1β and TNF-α in serum and hippocampus homogenate from the rats were detected by using ELISA. The expressions of peroxisome proliferator-activated-receptor γ (PPAR-γ) and nuclear factor-κB (NF-κB) in the hippocampus were determined by immunofluorescence and western blot. Results GBP reduced alcohol consumption, whereas increased water consumption and locomotor activity of rats. GBP was also able to decrease the levels of IL-1β and TNF-α in both serum and hippocampus, in addition to the expression of NF-κB in the hippocampus. Furthermore, these effects attributed to GBP were observed to disappear in the presence of bisphenol A diglycidyl ether (BADGE), a specific inhibitor of PPAR-γ. Conclusions Our findings revealed that GBP could activate PPAR-γ to suppress the NF-κB signaling pathway, contributing to the decrease of ethanol consumption and ethanol-induced neuroimmune responses.

scholarly journals NDRG1 regulates osteosarcoma cells via mediating the mitochondrial function and CSCs differentiation

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Tong Zhao ◽  
Ying Meng ◽  
Yongping Wang ◽  
Wenji Wang
Keyword(s):  
Stem Cells ◽  
Tumor Therapy ◽  
Anion Channel ◽  
Metastatic Potential ◽  
Peroxisome Proliferator ◽  
Voltage Dependent Anion Channel ◽  
Related Factors ◽  
Peroxisome Proliferator Activated Receptor ◽  
Voltage Dependent ◽  
Endothelial Growth Factor

Abstract Background Cancer stem cells (CSCs) are mainly contributed to malignancy metastatic potential and resistant therapy of osteosarcoma (OS). The mitochondria-related apoptosis was generally accepted as the target of tumor therapy. However, the effect of N-myc downstream-regulated gene 1 (NDRG1) on CSCs and mitochondrial health in OS is still unknown. Methods In OS cells, MG63 and U2OS, the siRNA of NDRG1 were conducted. Transwell, western blot, RT-qPCR, and mitochondria isolation were used to identify the effect of NDRG on OS cells and mitochondria. Moreover, the differentiation-related factors of CSCs were determined. Results After downregulation of NDRG1, the cell viability, invasion ability decreased whereas cell apoptosis increased. The expressions profiles of fibronectin, vimentin, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP) 2, MMP9, and MMP13 were downregulated, but E-cadherin expression level was upregulated by NDRG1 siRNA. At the same time, cytochrome (Cyt) C levels were increased in cytosol with the decreasing in mitochondria after siRNA treatment. The mitochondrial membrane potential (MMPs) was declined, and the function of mitochondria was impeded. The expressions of uncoupling proteins (UCP) 2, voltage dependent anion channel (VDAC), peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α, and cyclooxygenase (COX) 2 were downregulated by NDRG1 silencing. Moreover, NDRG performed its function primarily through the Wnt pathway and could regulate the differentiation of osteosarcoma stem cells. Conclusion Silencing of NDRG1 could damage the function of mitochondria, promote the CSCs differentiation, alleviating OS progression.

scholarly journals Blunted muscle mitochondrial responses to exercise training in older adults with HIV

2020 ◽  
Author(s):  
Catherine M Jankowski ◽  
Melissa P Wilson ◽  
Samantha MaWhinney ◽  
Jane Reusch ◽  
Leslie Knaub ◽  
...  
Keyword(s):  
Manganese Superoxide Dismutase ◽  
Citrate Synthase ◽  
Anion Channel ◽  
Peroxisome Proliferator ◽  
Voltage Dependent Anion Channel ◽  
Peroxisome Proliferator Activated Receptor ◽  
Manganese Superoxide ◽  
Before And After ◽  
Voltage Dependent ◽  
Exercise Induced

Abstract Background Muscle mitochondrial dysfunction associated with HIV and antiretroviral therapy (ART) may improve with exercise. Methods Muscle specimens obtained before and after 24 weeks of exercise in older PWH (n=18; ART >2 years) and uninfected controls (n=21) were analyzed for citrate synthase (CS) activity and complexes (C) I-V, manganese superoxide dismutase (MnSOD), peroxisome proliferator-activated receptor-γ coactivator-1 (PGC1α), and voltage-dependent anion channel 1 (VDAC1) content. Results Only controls had increased CS, MnSOD, PGC1 and CIV (P≤0.01; P< 0.01 vs PWH) after training. Conclusions The blunted mitochondrial adaptations to training in PWH suggests the need for different types of exercise-induced stimulation.

scholarly journals Atorvastatin protects against postoperative neurocognitive disorder via a peroxisome proliferator-activated receptor-gamma signaling pathway in mice

2020 ◽  
Vol 48 (5) ◽  
pp. 030006052092425
Author(s):  
Yinan Yang ◽  
Changwei Wei ◽  
Jinhu Liu ◽  
Danxu Ma ◽  
Chao Xiong ◽  
...  
Keyword(s):  
Mouse Model ◽  
Signaling Pathway ◽  
Underlying Mechanism ◽  
Peroxisome Proliferator ◽  
Neurocognitive Disorder ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Atorvastatin Treatment ◽  
Factor Α ◽  
Pparγ Expression

Objective Postoperative neurocognitive disorder (PND) is a main complication that is commonly seen postoperatively in elderly patients. The underlying mechanism remains unclear, although neuroinflammation has been increasingly observed in PND. Atorvastatin is a pleiotropic agent with proven anti-inflammatory effects. In this study, we investigated the effects of atorvastatin on a PND mouse model after peripheral surgery. Material and methods The mice were randomized into five groups. The PND models were established, and an open field test and fear condition test were performed. Hippocampal inflammatory cytokine expression was determined using ELISA. Peroxisome proliferator-activated receptor-gamma (PPARγ) expression in the hippocampus was tested using qRT-PCR and western blot analysis. Results On day 1 after surgery, inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, and interleukin-6 showed a significant increase in the hippocampus, with prominent cognitive impairment. Atorvastatin treatment improved cognitive function in the mouse model, attenuated neuroinflammation, and increased PPARγ expression in the hippocampus. However, treatment with the PPARγ antagonist GW9662 partially reversed the protective effects of atorvastatin. Conclusions These results indicated that atorvastatin improves several hippocampal functions and alleviates inflammation in PND mice after surgery, probably through a PPARγ-involved signaling pathway.

scholarly journals Twist2 contributes to cisplatin-resistance of ovarian cancer through the AKT/GSK-3β signaling pathway

2014 ◽  
Vol 7 (4) ◽  
pp. 1102-1108 ◽  
Author(s):  
TIAN WANG ◽  
YAN LI ◽  
ABIDAN TUERHANJIANG ◽  
WENWEN WANG ◽  
ZHANGYING WU ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Signaling Pathway ◽  
Cisplatin Resistance ◽  
Gsk 3Β

scholarly journals Anxa2 gene silencing attenuates obesity-induced insulin resistance by suppressing the NF-κB signaling pathway

2019 ◽  
Vol 316 (2) ◽  
pp. C223-C234 ◽  
Author(s):  
Yong Wang ◽  
Yun-Sheng Cheng ◽  
Xiao-Qiang Yin ◽  
Gang Yu ◽  
Ben-Li Jia
Keyword(s):  
Insulin Resistance ◽  
Gene Silencing ◽  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Cell Model ◽  
Global Scale ◽  
Differentially Expressed ◽  
Cytokine Signaling ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Insulin resistance (IR) continues to pose a major threat to public health due to its role in the pathogenesis of metabolic syndrome and its ever-increasing prevalence on a global scale. The aim of the current study was to investigate the efficacy of Anxa2 in obesity-induced IR through the mediation of the NF-κB signaling pathway. Microarray analysis was performed to screen differentially expressed genes associated with obesity. To verify whether Anxa2 was differentially expressed in IR triggered by obesity, IR mouse models were established in connection with a high-fat diet (HFD). In the mouse IR model, the role of differentially expressed Anxa2 in glycometabolism and IR was subsequently detected. To investigate the effect of Anxa2 on IR and its correlation with inflammation, a palmitic acid (PA)-induced IR cell model was established, with the relationship between Anxa2 and the NF-κB signaling pathway investigated accordingly. Anxa2 was determined to be highly expressed in IR. Silencing Anxa2 was shown to inhibit IR triggered by obesity. When Anxa2 was knocked down, elevated expression of phosphorylated insulin receptor substrate 1 (IRS1), IRS1 and peroxisome proliferator-activated receptor coactivator-1a, and glucose tolerance and insulin sensitivity along with 2-deoxy-d-glucose uptake was detected, whereas decreased expression of suppressor of cytokine signaling 3, IL-6, IL-1β, TNF-α, and p50 was observed. Taken together, the current study ultimately demonstrated that Anxa2 may be a novel drug strategy for IR disruption, indicating that Anxa2 gene silencing is capable of alleviating PA or HFD-induced IR and inflammation through its negative regulatory role in the process of p50 nuclear translocation of the NF-κB signaling pathway.

scholarly journals HOTTIP-miR-205-ZEB2 Axis Confers Cisplatin Resistance to Ovarian Cancer Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Yu-Jie Dong ◽  
Wei Feng ◽  
Yan Li
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Clinical Problem ◽  
Ovarian Cancer Cells ◽  
Stem Cell Markers ◽  
Gene Target ◽  
Gynecological Malignancy ◽  
Clonogenic Potential ◽  
Resistant Cells

Ovarian cancer is a deadly gynecological malignancy with resistance to cisplatin a major clinical problem. We evaluated a role of long non-coding (lnc) RNA HOTTIP (HOXA transcript at the distal tip) in the cisplatin resistance of ovarian cancer cells, using paired cisplatin sensitive and resistant A2780 cells along with the SK-OV-3 cells. HOTTIP was significantly elevated in cisplatin resistant cells and its silencing reversed the cisplatin resistance of resistant cells. HOTTIP was found to sponge miR-205 and therefore HOTTIP silenced cells had higher levels of miR-205. Downregulation of miR-205 could attenuate HOTTIP-silencing effects whereas miR-205 upregulation in resistant cells was found to re-sensitize cells to cisplatin. HOTTIP silencing also led to reduced NF-κB activation, clonogenic potential and the reduced expression of stem cell markers SOX2, OCT4, and NANOG, an effect that could be attenuated by miR-205. Finally, ZEB2 was identified as the gene target of miR-205, thus completing the elucidation of HOTTIP-miR-205-ZEB2 as the novel axis which is functionally involved in the determination of cisplatin resistance in ovarian cancer cells.

Sign in / Sign up

Export Citation Format

Share Document