scholarly journals Plasminogen Kringle 5 Induces Endothelial Cell Apoptosis by Triggering a Voltage-dependent Anion Channel 1 (VDAC1) Positive Feedback Loop

2014 ◽  
Vol 289 (47) ◽  
pp. 32628-32638 ◽  
Author(s):  
Lei Li ◽  
Ya-Chao Yao ◽  
Xiao-Qiong Gu ◽  
Di Che ◽  
Cai-Qi Ma ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Positive Feedback ◽  
Cell Apoptosis ◽  
Feedback Loop ◽  
Anion Channel ◽  
Endothelial Cell Apoptosis ◽  
Voltage Dependent Anion Channel ◽  
Positive Feedback Loop ◽  
Kringle 5 ◽  
Voltage Dependent

Voltage‐dependent anion channel 1 is involved in endostatin‐induced endothelial cell apoptosis

2008 ◽  
Vol 22 (8) ◽  
pp. 2809-2820 ◽  
Author(s):  
Shaopeng Yuan ◽  
Yan Fu ◽  
Xiaofeng Wang ◽  
Hubing Shi ◽  
Yujie Huang ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Anion Channel ◽  
Endothelial Cell Apoptosis ◽  
Voltage Dependent Anion Channel ◽  
Voltage Dependent

scholarly journals VDAC: old protein with new roles in diabetes

2012 ◽  
Vol 303 (10) ◽  
pp. C1055-C1060 ◽  
Author(s):  
Koh Sasaki ◽  
Reshma Donthamsetty ◽  
Michael Heldak ◽  
Young-Eun Cho ◽  
Brian T. Scott ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Mitochondrial Permeability Transition ◽  
Anion Channel ◽  
Capillary Density ◽  
Cardiac Ischemia ◽  
Diabetic Mice ◽  
Endothelial Cell Apoptosis ◽  
Voltage Dependent Anion Channel ◽  
Mptp Opening

A decrease in capillary density due to an increase in endothelial cell apoptosis in the heart is implicated in cardiac ischemia in diabetes. The voltage-dependent anion channel (VDAC) plays a crucial role in the regulation of mitochondrial metabolic function and mitochondria-mediated apoptosis. This study is designed to examine the role of VDAC in coronary endothelial dysfunction in diabetes. Endothelial cells (ECs) were more apoptotic in diabetic left ventricle of diabetic mice and mouse coronary ECs (MCECs) isolated from diabetic mice exhibited significantly higher mitochondrial Ca2+ concentration and VDAC protein levels than control MCECs. The expression of VDAC-short hairpin RNA (shRNA) not only decreased the resting mitochondrial Ca2+ concentration but also attenuated mitochondrial Ca2+ uptake in diabetic MCECs. Furthermore, the downregulation of VDAC in diabetic MCECs significantly decreased mitochondrial superoxide anion (O2−) production and the activity of the mitochondrial permeability transition pore (mPTP) opening (an indirect indicator of cell apoptosis) toward control levels. These data suggest that the increased VDAC level in diabetic MCECs is responsible for increased mitochondrial Ca2+ concentration, mitochondrial O2− production, and mPTP opening activity. Normalizing VDAC protein level may help to decrease endothelial cell apoptosis, increase capillary density in the heart, and subsequently decrease the incidence of cardiac ischemia in diabetes.

P53/miR-34a/SIRT1 Positive Feedback Loop regulates cell proliferation and promotes cell apoptosis in the termination stage of liver regeneration.

2021 ◽  
Author(s):  
Junhua Gong ◽  
Minghua Cong ◽  
Hao Wu ◽  
Menghao Wang ◽  
He Bai ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Liver Regeneration ◽  
Positive Feedback ◽  
Cell Apoptosis ◽  
Feedback Loop ◽  
Late Phase ◽  
Liver Weight ◽  
Positive Feedback Loop ◽  
And Function ◽  
Shed Light

Abstract Background The capacity of the liver to restore its architecture and function assures good prognoses of patients who suffer serious hepatic injury or cancer resection. In our study, we found that the P53/miR-34a/SIRT1 positive feedback loop has a remarkable negative regulatory effect, which is related to the termination of liver regeneration. Here, we described how P53/miR-34a/SIRT1 positive feedback loop controls liver regeneration and its possible relationship with liver cancer.Method We performed partial hepatectomy (PH) in mice transfected with adenovirus (Ade) overexpressing P53 and adenovirus-associated virus (AAV) knock-downing miR-34a. LR was analyzed by liver weight/body weight, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and cell proliferation, and the related cellular signals were investigated. Bile acid (BA) levels during LR were analyzed by metabolomics of bile acids. Results We found that the P53/miR-34a/SIRT1 positive feedback loop was activated in the late phase of LR. Overexpression of P53 terminated LR early and enhanced P53/miR-34a/SIRT1 positive feedback loop expression and its proapoptotic effect. Mice from the Ade-P53 group showed smaller livers and higher levels of serum ALT and AST than control mice. While knock-down of miR-34a abolished P53/miR-34a/SIRT1 positive feedback loop during LR. Mice from anti-miR-34a group showed larger livers and lower levels of PCNA-positive cells than control mice. T-β-MCA increased gradually during LR and peaked at 7 days after PH. T-β-MCA inhibited cell proliferation and promoted cell apoptosis via facilitating the P53/miR-34a/SIRT1 positive feedback loop during LR by suppressing FXR/SHP. Conclusion The P53/miR-34a/SIRT1 positive feedback loop plays an important role in the termination of LR. Our findings shed light on the molecular and metabolic mechanisms of LR termination and provide a potential therapeutic alternative for treating P53-wild-type HCC patients.

scholarly journals Leukemia Mediated Endothelial Cell Activation Modulates Leukemia Cell Susceptibility to Chemotherapy through a Positive Feedback Loop Mechanism

PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e60823 ◽  
Author(s):  
Bahareh Pezeshkian ◽  
Christopher Donnelly ◽  
Kelley Tamburo ◽  
Timothy Geddes ◽  
Gerard J. Madlambayan
Keyword(s):  
Endothelial Cell ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Cell Activation ◽  
Leukemia Cell ◽  
Endothelial Cell Activation ◽  
Positive Feedback Loop

APP/PS1 Gene-Environment Noise Interaction Aggravates AD-like Neuropathology in Hippocampus Via Activation of the VDAC1 Positive Feedback Loop

2021 ◽  
Vol 18 (1) ◽  
pp. 14-24
Author(s):  
Huimin Chi ◽  
Qingfeng Zhai ◽  
Ming Zhang ◽  
Donghong Su ◽  
Wa Cao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Noise Exposure ◽  
Glycogen Synthase ◽  
Amyloid Β ◽  
Environmental Noise ◽  
Voltage Dependent Anion Channel ◽  
Positive Feedback Loop ◽  
The Impact

Background: Environmental risk factors, including environmental noise stress, and genetic factors, have been associated with the occurrence and development of Alzheimer’s disease (AD). However, the exact role and mechanism of AD-like pathology induced by environment-gene interactions between environmental noise and APP/PS1 gene remain elusive. Methods: Herein, we investigated the impact of chronic noise exposure on AD-like neuropathology in APP/PS1 transgenic mice. The Morris water maze (MWM) task was conducted to evaluate AD-like changes. The hippocampal phosphorylated Tau, amyloid-β (Aβ), and neuroinflammation were assessed. We also assessed changes in positive feedback loop signaling of the voltage-dependent anion channel 1 (VDAC1) to explore the potential underlying mechanism linking AD-like neuropathology to noise-APP/PS1 interactions. Results: Long-term noise exposure significantly increased the escape latency and the number of platform crossings in the MWM task. The Aβ overproduction was induced in the hippocampus of APP/PS1 mice, along with the increase of Tau phosphorylation at Ser396 and Thr231 and the increase of the microglia and astrocytes markers expression. Moreover, the VDAC1-AKT (protein kinase B)-GSK3β (glycogen synthase kinase 3 beta)-VDAC1 signaling pathway was abnormally activated in the hippocampus of APP/PS1 mice after noise exposure. Conclusion: Chronic noise exposure and APP/PS1 overexpression may synergistically exacerbate cognitive impairment and neuropathological changes that occur in AD. This interaction may be mediated by the positive feedback loop of the VDAC1-AKT-GSK3β-VDAC1 signaling pathway.

scholarly journals Hexokinase 2 dimerization and interaction with voltage‐dependent anion channel promoted resistance to cell apoptosis induced by gemcitabine in pancreatic cancer

2019 ◽  
Vol 8 (13) ◽  
pp. 5903-5915 ◽  
Author(s):  
Kun Fan ◽  
Zhiyao Fan ◽  
He Cheng ◽  
Qiuyi Huang ◽  
Chao Yang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Apoptosis ◽  
Anion Channel ◽  
Voltage Dependent Anion Channel ◽  
Hexokinase 2 ◽  
Voltage Dependent

scholarly journals The Voltage-dependent Anion Channel Is a Receptor for Plasminogen Kringle 5 on Human Endothelial Cells

2003 ◽  
Vol 278 (29) ◽  
pp. 27312-27318 ◽  
Author(s):  
Mario Gonzalez-Gronow ◽  
Theodosia Kalfa ◽  
Carrie E. Johnson ◽  
Govind Gawdi ◽  
Salvatore V. Pizzo
Keyword(s):  
Endothelial Cells ◽  
Anion Channel ◽  
Human Endothelial Cells ◽  
Voltage Dependent Anion Channel ◽  
Kringle 5 ◽  
Voltage Dependent

scholarly journals Voltage-Dependent Anion Channel-1, a Possible Ligand of Plasminogen Kringle 5

PLoS ONE ◽  
2016 ◽  
Vol 11 (10) ◽  
pp. e0164834 ◽  
Author(s):  
Yin-ku Liang ◽  
Liu-jiao Bian
Keyword(s):  
Anion Channel ◽  
Voltage Dependent Anion Channel ◽  
Kringle 5 ◽  
Voltage Dependent
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