scholarly journals Role of Nrf2 and Its Activators in Cardiocerebral Vascular Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-19
Author(s):  
Liangkai Cheng ◽  
Hong Zhang ◽  
Fang Wu ◽  
Zhongqiu Liu ◽  
Yuanyuan Cheng ◽  
...  
Keyword(s):  
Vascular Disease ◽  
Signaling Pathway ◽  
Redox Regulation ◽  
Antioxidant Response ◽  
Pathological Process ◽  
Cellular Damage ◽  
Common Disease ◽  
High Morbidity ◽  
Therapeutic Drugs

Cardiocerebral vascular disease (CCVD) is a common disease with high morbidity, disability, and mortality. Oxidative stress (OS) is closely related to the progression of CCVD. Abnormal redox regulation leads to OS and overproduction of reactive oxygen species (ROS), which can cause biomolecular and cellular damage. The Nrf2/antioxidant response element (ARE) signaling pathway is one of the most important defense systems against exogenous and endogenous OS injury, and Nrf2 is regarded as a vital pharmacological target. The complexity of the CCVD pathological process and the current difficulties in conducting clinical trials have hindered the development of therapeutic drugs. Furthermore, little is known about the role of the Nrf2/ARE signaling pathway in CCVD. Clarifying the role of the Nrf2/ARE signaling pathway in CCVD can provide new ideas for drug design. This review details the recent advancements in the regulation of the Nrf2/ARE system and its role and activators in common CCVD development.

scholarly journals Inactivation of the Wnt/β-catenin signaling pathway underlies inhibitory role of microRNA-129-5p in epithelial–mesenchymal transition and angiogenesis of prostate cancer by targeting ZIC2

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhenming Jiang ◽  
Yuxi Zhang ◽  
Xi Chen ◽  
Pingeng Wu ◽  
Dong Chen
Keyword(s):  
Prostate Cancer ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Common Disease ◽  
Vascular Endothelial ◽  
Mesenchymal Transition ◽  
Du145 Cells ◽  
Endothelial Growth Factor ◽  
E Cadherin

Abstract Background Prostate cancer (PCa) is a common disease that often occurs among older men and a frequent cause of malignancy associated death in this group. microRNA (miR)-129-5p has been identified as an essential regulator with a significant role in the prognosis of PC. Therefore, this study aimed to investigate roles of miR-129-5p in PCa. Methods Microarray analysis was conducted to identify PCa-related genes. The expression of miR-129-5p and ZIC2 in PCa tissues was investigated. To understand the role of miR-129-5p and ZIC2 in PCa, DU145 cells were transfected with mimic or inhibitor of miR-129-5p, or si-ZIC2 and the expression of Wnt, β-catenin, E-cadherin, vimentin, N-cadherin, vascular endothelial growth factor (VEGF), and CD31, as well as the extent of β-catenin phosphorylation was determined. In addition, cell proliferation, migration, invasion, angiogenesis, apoptosis and tumorigenesis were detected. Results miR-129-5p was poorly expressed and ZIC2 was highly expressed in PCa tissues. Down-regulation of ZIC2 or overexpression of miR-129-5p reduced the expression of ZIC2, Wnt, β-catenin, N-cadherin, vimentin, and β-catenin phosphorylation but increased the expression of E-cadherin. Importantly, miR-129-5p overexpression significantly reduced cell migration, invasion, angiogenesis and tumorigenesis while increasing cell apoptosis. Conclusions The findings of the present study indicated that overexpression of miR-129-5p or silencing of ZIC2 could inhibit epithelial–mesenchymal transition (EMT) and angiogenesis in PCa through blockage of the Wnt/β-catenin signaling pathway.

scholarly journals Aortic dissection is associated with reduced polycystin-1 expression, an abnormality that leads to increased ERK phosphorylation in vascular smooth muscle cells

2016 ◽  
Author(s):  
J. Feng ◽  
S. Ge ◽  
L. Zhang ◽  
H. Che ◽  
C. Liang
Keyword(s):  
Smooth Muscle ◽  
Aortic Dissection ◽  
Vascular Smooth Muscle ◽  
Signaling Pathway ◽  
Intracellular Signaling ◽  
High Morbidity ◽  
Biological Processes ◽  
Phenotypic Switch ◽  
Erk Phosphorylation

The vascular smooth muscle cell (VSMC) phenotypic switch is a key pathophysiological change in various cardiovascular diseases, such as aortic dissection (AD), with a high morbidity. Polycystin-1 (PC1) is significantly downregulated in the VSMCs of AD patients. PC1 is an integral membrane glycoprotein and kinase that regulates different biological processes, including cell proliferation, apoptosis, and cell polarity. However, the role of PC1 in intracellular signaling pathways remains poorly understood. In this study, PC1 downregulation in VSMCs promoted the expression of SM22α, ACTA2 and calponin 1 (CNN1) proteins. Furthermore, PC1 downregulation in VSMCs upregulated phospho-MEK, phospho-ERK and myc, but did not change phospho-JNK and phospho-p38. These findings suggest that the MEK/ERK/myc signaling pathway is involved in PC1-mediated human VSMC phenotypic switch. Opposite results were observed when an ERK inhibitor was used in VSMCs downregulated by PC1. When the C-terminal domain of PC1 (PC1 C-tail) was overexpressed in VSMCs, the expression levels of phosphor-ERK, myc, SM22α, ACTA2 and CNN1 proteins were downregulated. The group with the overexpressed mutant protein (S4166A) in the PC1 C-tail showed similar results to the group with the downregulated PC1 in VSMCs. These results suggest that the Ser at the 4166 site in PC1 is crucial in the PC1 mediated MEK/ERK/myc signaling pathway, which might be the key pathophysiological cause of AD.

A Study On The Correlation Between Slit2/Robo1 Signaling Pathway Proteins And Polymyositis/Dermatomyositis

2020 ◽  
Vol 20 ◽  
Author(s):  
Ke-Xia Chai ◽  
Yu-Qi Chen ◽  
Ling-Shuang Kong ◽  
Pei-Lin Fan ◽  
Xia Yuan ◽  
...  
Keyword(s):  
Vascular Disease ◽  
Signaling Pathway ◽  
Muscle Tissue ◽  
Control Group ◽  
Healthy Controls ◽  
Positive Expression ◽  
Study Results ◽  
The Difference ◽  
Pm 10

Aims: To investigate the role of Slit2 and Robo1 during the vascular disease of Polymyositis (PM) / dermatomyositis (DM). Background : PM and DM are non-suppurative inflammatory myopathies that mainly invade the skeletal muscles. Objective: This study attempted to explore the specific mechanism of Slit2/Robo1 signaling pathway proteins during the vascular disease of PM/DM. Methods: The mRNA expressions of Slit2 and Robo1 in the muscle tissue were detected by RT-qPCR between newly-diagnosed PM/DM patients and healthy controls. The number of Slit2 and Robo1 positive cells in the serial sections of muscle paraffin tissues was measured by immunohistochemistry in 10 patients with PM, 10 patients with DM and 20 healthy controls. Results: The study results revealed that the mRNA expressions of Slit2 and Robo1 in muscle tissue in the PM and DM groups were higher than that in the control group (P<0.05). The positive expression rates of Slit2 and Robo1 in muscle tissue in the PM and DM groups were 80.0%, 80.0%, 70.0% and 70.0%, respectively. The difference was statistically significant (P<0.001), when compared to the control group (the positive expression rates were 0% and 10%, respectively). Conclusion: The activation of the Slit2/Robo1 signaling pathway is an important mechanism leading to the development of PM/DM.

scholarly journals Screening and Role of circRNAs in Vulvar Lichen Sclerosus

2021 ◽  
Author(s):  
min yang ◽  
Kailu Sun ◽  
Jianmin Chang
Keyword(s):  
Signaling Pathway ◽  
Leukemia Virus ◽  
Lichen Sclerosus ◽  
Pathological Process ◽  
Differentially Expressed ◽  
Human T Cell ◽  
Healthy Female ◽  
T Cell Leukemia Virus ◽  
Vulvar Lichen Sclerosus

Abstract Objective：The aim of this study was to investigate the expression profile of circRNA in Vulvar Lichen Sclerosus, and to identify the underlying core genes of Vulvar Lichen Sclerosus.Methods：rRNA removal was used for sequencing, and mRNA, lncRNA and circRNA differentially expressed between 20 groups of VLS tissues and 20 groups of healthy female vulva skin tissues were screened. Bioinformatics analysis was used to analyze its potential function.Results：A total of 1545 differentially expressed mRNAs were assessed in VLS patients, of which 1541 were upregulated and 1004 were down-regulated; A total of 1453 differentially expressed lncRNAs were assessed, of which 812 were up-regulated and 641 were down-regulated. A total of 79 differentially expressed circRNAs were assessed, of which 54 were upregulated and 25 were down-regulated. The differential expression of CircRNA is closely related to biological processes and molecular functions. The differences in circRNA were mainly related to the "human T-cell leukemia virus 1 infection" signaling pathway and the "axon guidance" signaling pathway.Conclusion：This study identified the profile of abnormal regulation of circRNA in VLS. Biological informatics analysis showed that the dysregulation of circRNAs could be related to the pathogenesis and pathological process of VLS.

Activation of cytochrome c to a peroxidase compound I-type intermediate by H2O2: relevance to redox signalling in apoptosis

2004 ◽  
Vol 71 ◽  
pp. 97-106 ◽  
Author(s):  
Mark Burkitt ◽  
Clare Jones ◽  
Andrew Lawrence ◽  
Peter Wardman
Keyword(s):  
Cytochrome C ◽  
Hydroxyl Radical ◽  
Redox Regulation ◽  
Chemotherapeutic Agents ◽  
Tyrosyl Radical ◽  
Compound I ◽  
Definitive Evidence ◽  
Enhanced Production ◽  
Physico Chemical

The release of cytochrome c from mitochondria during apoptosis results in the enhanced production of superoxide radicals, which are converted to H2O2 by Mn-superoxide dismutase. We have been concerned with the role of cytochrome c/H2O2 in the induction of oxidative stress during apoptosis. Our initial studies showed that cytochrome c is a potent catalyst of 2′,7′-dichlorofluorescin oxidation, thereby explaining the increased rate of production of the fluorophore 2′,7′-dichlorofluorescein in apoptotic cells. Although it has been speculated that the oxidizing species may be a ferryl-haem intermediate, no definitive evidence for the formation of such a species has been reported. Alternatively, it is possible that the hydroxyl radical may be generated, as seen in the reaction of certain iron chelates with H2O2. By examining the effects of radical scavengers on 2′,7′-dichlorofluorescin oxidation by cytochrome c/H2O2, together with complementary EPR studies, we have demonstrated that the hydroxyl radical is not generated. Our findings point, instead, to the formation of a peroxidase compound I species, with one oxidizing equivalent present as an oxo-ferryl haem intermediate and the other as the tyrosyl radical identified by Barr and colleagues [Barr, Gunther, Deterding, Tomer and Mason (1996) J. Biol. Chem. 271, 15498-15503]. Studies with spin traps indicated that the oxo-ferryl haem is the active oxidant. These findings provide a physico-chemical basis for the redox changes that occur during apoptosis. Excessive changes (possibly catalysed by cytochrome c) may have implications for the redox regulation of cell death, including the sensitivity of tumour cells to chemotherapeutic agents.

285: The Role of the NF-κB Signaling Pathway in the Pathogenesis of Interstitial Cystitis

2006 ◽  
Vol 175 (4S) ◽  
pp. 95-95
Author(s):  
Raymond R. Rackley ◽  
Mei Kuang ◽  
Ashwin A. Vaze ◽  
Joseph Abdelmalak ◽  
Sandip P. Vasavada ◽  
...  
Keyword(s):  
Interstitial Cystitis ◽  
Signaling Pathway

Quantitative accuracy of serotonergic neurotrans-mission imaging with high-resolution 123I SPECT

2004 ◽  
Vol 43 (06) ◽  
pp. 185-189 ◽  
Author(s):  
J. T. Kuikka
Keyword(s):  
High Resolution ◽  
Scatter Correction ◽  
Region Of Interest ◽  
Binding Potential ◽  
Partial Volume ◽  
Therapeutic Drugs ◽  
Quantitative Accuracy ◽  
Critical Error ◽  
Statistical Noise

Summary Aim: Serotonin transporter (SERT) imaging can be used to study the role of regional abnormalities of neurotransmitter release in various mental disorders and to study the mechanism of action of therapeutic drugs or drugs’ abuse. We examine the quantitative accuracy and reproducibility that can be achieved with high-resolution SPECT of serotonergic neurotransmission. Method: Binding potential (BP) of 123I labeled tracer specific for midbrain SERT was assessed in 20 healthy persons. The effects of scatter, attenuation, partial volume, mis-registration and statistical noise were estimated using phantom and human studies. Results: Without any correction, BP was underestimated by 73%. The partial volume error was the major component in this underestimation whereas the most critical error for the reproducibility was misplacement of region of interest (ROI). Conclusion: The proper ROI registration, the use of the multiple head gamma camera with transmission based scatter correction introduce more relevant results. However, due to the small dimensions of the midbrain SERT structures and poor spatial resolution of SPECT, the improvement without the partial volume correction is not great enough to restore the estimate of BP to that of the true one.

Sign in / Sign up

Export Citation Format

Share Document