scholarly journals Hypoxia Inducible Factors as Central Players in the Pathogenesis and Pathophysiology of Cardiovascular Diseases

2021 ◽  
Vol 8 ◽  
Author(s):  
Emilio Y. Lucero García Rojas ◽  
Cleva Villanueva ◽  
Richard A. Bond
Keyword(s):  
Treatment Strategies ◽  
Main Function ◽  
Oxygen Species ◽  
Industrialized Countries ◽  
Hypoxia Inducible Factors ◽  
Compensatory Mechanisms ◽  
Irreversible Damage ◽  
Nutrient Delivery ◽  
Hypoxic State ◽  
Increased Blood Flow

Cardiovascular (CV) diseases are the major cause of death in industrialized countries. The main function of the CV system is to deliver nutrients and oxygen to all tissues. During most CV pathologies, oxygen and nutrient delivery is decreased or completely halted. Several mechanisms, including increased oxygen transport and delivery, as well as increased blood flow are triggered to compensate for the hypoxic state. If the compensatory mechanisms fail to sufficiently correct the hypoxia, irreversible damage can occur. Thus, hypoxia plays a central role in the pathogenesis and pathophysiology of CV diseases. Hypoxia inducible factors (HIFs) orchestrate the gene transcription for hundreds of proteins involved in erythropoiesis, glucose transport, angiogenesis, glycolytic metabolism, reactive oxygen species (ROS) handling, cell proliferation and survival, among others. The overall regulation of the expression of HIF-dependent genes depends on the severity, duration, and location of hypoxia. In the present review, common CV diseases were selected to illustrate that HIFs, and proteins derived directly or indirectly from their stabilization and activation, are related to the development and perpetuation of hypoxia in these pathologies. We further classify CV diseases into acute and chronic hypoxic states to better understand the temporal relevance of HIFs in the pathogenesis, disease progression and clinical outcomes of these diseases. We conclude that HIFs and their derived factors are fundamental in the genesis and progression of CV diseases. Understanding these mechanisms will lead to more effective treatment strategies leading to reduced morbidity and mortality.

scholarly journals Role of NADPH Oxidase-Mediated Reactive Oxygen Species in Podocyte Injury

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Shan Chen ◽  
Xian-Fang Meng ◽  
Chun Zhang
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Epithelial To Mesenchymal Transition ◽  
Kidney Diseases ◽  
Treatment Strategies ◽  
Reactive Oxygen ◽  
Glomerular Sclerosis ◽  
Oxygen Species ◽  
Podocyte Injury ◽  
Mesenchymal Transition

Proteinuria is an independent risk factor for end-stage renal disease (ESRD) (Shankland, 2006). Recent studies highlighted the mechanisms of podocyte injury and implications for potential treatment strategies in proteinuric kidney diseases (Zhang et al., 2012). Reactive oxygen species (ROS) are cellular signals which are closely associated with the development and progression of glomerular sclerosis. NADPH oxidase is a district enzymatic source of cellular ROS production and prominently expressed in podocytes (Zhang et al., 2010). In the last decade, it has become evident that NADPH oxidase-derived ROS overproduction is a key trigger of podocyte injury, such as renin-angiotensin-aldosterone system activation (Whaley-Connell et al., 2006), epithelial-to-mesenchymal transition (Zhang et al., 2011), and inflammatory priming (Abais et al., 2013). This review focuses on the mechanism of NADPH oxidase-mediated ROS in podocyte injury under different pathophysiological conditions. In addition, we also reviewed the therapeutic perspectives of NADPH oxidase in kidney diseases related to podocyte injury.

Discovery of new chiral sulfonamides bearing benzoxadiazole as HIF inhibitors for non-small cell lung cancer therapy: design, microwave-assisted synthesis, binding affinity, in vitro antitumoral activities and in silico studies

2022 ◽  
Author(s):  
Demet Taşdemir ◽  
Ayşegül Karaküçük-İyidoğan ◽  
Yasemin Saygideger ◽  
EMİNE Elçin Emre ◽  
Tuğba Taşkın-Tok ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Treatment Strategies ◽  
Microwave Assisted Synthesis ◽  
Hypoxia Inducible Factors ◽  
Small Cell Lung ◽  
Microwave Assisted ◽  
In Silico Studies ◽  
Lung Cancer Therapy ◽  
Therapy Design

Hypoxia-inducible factors (HIF), one of the targeted treatment strategies with a rising promise in lung cancer, are known to play a role in tumor growth and other oncogenic properties in...

scholarly journals PGI synthase overexpression protects against bleomycin-induced mortality and is associated with increased Nqo 1 expression

2011 ◽  
Vol 301 (4) ◽  
pp. L615-L622 ◽  
Author(s):  
Weisong Zhou ◽  
Dustin R. Dowell ◽  
Mark W. Geraci ◽  
Timothy S. Blackwell ◽  
Robert D. Collins ◽  
...  
Keyword(s):  
Airway Epithelium ◽  
Death Rate ◽  
Treatment Strategies ◽  
Oxygen Species ◽  
In Vitro Experiments ◽  
Wild Type ◽  
Potential Therapeutic Target ◽  
First Time

The mortality rate for acute lung injury (ALI) is reported to be between 35–40%, and there are very few treatment strategies that improve the death rate from this condition. Previous studies have suggested that signaling through the prostaglandin (PG) I2 receptor may protect against bleomycin-induced ALI in mice. We found that mice that overexpress PGI synthase (PGIS) in the airway epithelium were significantly protected against bleomycin-induced mortality and had reduced parenchymal consolidation, apoptosis of lung tissue, and generation of F2-isoprostanes compared with littermate wild-type controls. In addition, we show for the first time in both in vivo and in vitro experiments that PGI2 induced the expression of NADP (H): quinoneoxidoreductase 1 (Nqo 1), an enzyme that prevents the generation of reactive oxygen species. PGI2 induction of Nqo 1 provides a possible novel mechanism by which this prostanoid protects against bleomycin-induced mortality and identifies a potential therapeutic target for human ALI.

scholarly journals β-Elemene Triggers ROS-dependent Apoptosis in Glioblastoma Cells Through Suppressing STAT3 Signaling Pathway

2021 ◽  
Vol 27 ◽  
Author(s):  
Shi-zhong Cai ◽  
Qian-wei Xiong ◽  
Li-na Zhao ◽  
Yi-ting Ji ◽  
Zheng-xiang Luo ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Caspase 3 ◽  
Treatment Strategies ◽  
Oxygen Species ◽  
Glioblastoma Cells ◽  
Western Blot Assay ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Apoptotic Activity ◽  
Induced Apoptosis

Glioblastoma is one of the most aggressive primary brain tumors with few treatment strategies. β-Elemene is a sesquiterpene known to have broad spectrum antitumor activity against various cancers. However, the signaling pathways involved in β-elemene induced apoptosis of glioblastoma cells remains poorly understood. In this study, we reported that β-elemene exhibited antiproliferative activity on U87 and SHG-44 cells, and induced cell death through induction of apoptosis. Incubation of these cells with β-elemene led to the activation of caspase-3 and generation of reactive oxygen species (ROS). Western blot assay showed that β-elemene suppressed phosphorylation of STAT3, and subsequently down-regulated the activation of p-JAK2 and p-Src. Moreover, pre-incubation of cells with ROS inhibitor N-acetyl-L-cysteine (NAC) significantly reversed β-elemene-mediated apoptosis effect and down-regulation of JAK2/Src-STAT3 signaling pathway. Overall, our findings implied that generation of ROS and suppression of STAT3 signaling pathway is critical for the apoptotic activity of β-elemene in glioblastoma cells.

scholarly journals Reactive Oxygen Species in Neurodegenerative Diseases: Implications in Pathogenesis and Treatment Strategies

2021 ◽  
Author(s):  
Johnson Olaleye Oladele ◽  
Adenike T. Oladiji ◽  
Oluwaseun Titilope Oladele ◽  
Oyedotun M. Oyeleke
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Protein Misfolding ◽  
Critical Role ◽  
Treatment Strategies ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
The Brain

Neurodegenerative diseases are debilitating disorders which compromise motor or cognitive functions and are rapidly becoming a global communal disorder with over 46.8 million people suffering dementia worldwide. Aetiological studies have showed that people who are exposed to agricultural, occupational and environmental toxic chemicals that can interfere and degenerate dopaminergic neurons are prone to developing neurodegenerative diseases such as Parkinson Disease. The complex pathogenesis of the neurodegenerative diseases remains largely unknown; however, mounting evidence suggests that oxidative stress, neuroinflammation, protein misfolding, and apoptosis are the hallmarks of the diseases. Reactive oxygen species (ROS) are chemically reactive molecules that have been implicated in the pathogenesis of neurodegenerative diseases. ROS play a critical role as high levels of oxidative stress are commonly observed in the brain of patients with neurodegenerative disorders. This chapter focus on the sources of ROS in the brain, its involvement in the pathogenesis of neurodegenerative diseases and possible ways to mitigate its damaging effects in the affected brain.

scholarly journals Petri nets and ODE as complementary tools in analysis of signaling pathways

10.29007/542h ◽  
2019 ◽  
Author(s):  
Daria Kogut ◽  
Kaja Gutowska ◽  
Aleksandra Poterała-Hejmo ◽  
Jarosław Śmieja ◽  
Dorota Formanowicz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Ribosomal Subunit ◽  
Antioxidant Systems ◽  
Main Function ◽  
Oxygen Species ◽  
Radical Oxygen Species ◽  
Apoptosis Pathway ◽  
Elongation Process ◽  
Post Transcriptional Regulation

Regulation of gene expression is one of the most important problems analyzed in systems biology. It involves, among other, interactions of mRNA with miRNA - a small (21-25 nt) single–stranded non–coding RNA molecule. Its main function is post-transcriptional regulation of gene expression leading to gene silencing. It is achieved either by inhibition of translation or by degradation of mRNA. The detailed mechanisms employed include inhibition of attaching the 60s ribosomal subunit, premature ribosome drop-off or inhibition of protein elongation process, cleavage of mRNA or destabilization of mRNA. Another mechanism of regulation of gene expression involves reactive oxygen species (ROS - radical and non-radical oxygen species formed by the partial reduction of oxygen) which, being released from mitochondrium cytochrome C and inducing DNA damage, induce the apoptosis pathway. ROS level can be regulated by antioxidant systems existing in a cell. This paper presents analysis of a model of gene regulation based on these molecules, in which Petri net is used to find the key reactions and, subsequently, an ODE-based model is used to verify these conclusions.

scholarly journals Transcriptome sequencing of circular RNA reveals a novel circular RNA-has_circ_0114427 in the regulation of inflammation in acute kidney injury

2020 ◽  
Vol 134 (2) ◽  
pp. 139-154 ◽  
Author(s):  
Yiling Cao ◽  
Xuhua Mi ◽  
Dongmei Zhang ◽  
Zheng Wang ◽  
Yongdi Zuo ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Expression Profile ◽  
Cell Model ◽  
Early Stage ◽  
Treatment Strategies ◽  
Kidney Injury ◽  
Circular Rna ◽  
Progressive Increase ◽  
Circular Rnas ◽  
Main Function

Abstract Acute kidney injury (AKI) is a common serious syndrome characterized by rapid decrease of glomerular filtration rate and the progressive increase of serum creatinine. Circular RNAs (circRNAs) are regulatory RNAs that recently became popular among various diseases. However, the expression profile and function of circRNAs in AKI remain largely unknown. The main function of circRNAs is acting as competing endogenous RNAs (ceRNAs) by binding with microRNAs (miRNAs), as indicated by recent research. In the present study, we established cisplatin-induced AKI model in mice and isolated renal tubular tissues to extract circRNAs for next-generation sequencing (NGS) and bioinformatics analysis. We analyzed the composition, distribution and Gene Ontology terms of circRNAs in cisplatin-induced AKI and revealed differentially expressed circRNAs related to AKI. By finding homologous genes between mouse and human, we identified circRNA- circ-0114427 in humans. We further investigated its function in AKI cell model. Circ-0114427 expression was significantly up-regulated in different AKI cell models. Knockdown of circ-0114427 indicated that circ-0114427 bound to miR-494 as a miRNA sponge to regulate ATF3 expression and further affected the expression of downstream cytokine IL-6. Circ-0114427 regulates inflammatory progression in AKI’s early stage via circ-0114427/miR-494/ATF3 pathway. Our findings reveal the expression profile of circRNAs in cisplatin-induced AKI and provide a novel insight into the regulatory mechanism of circRNAs, which may become a new molecular target resource for early diagnosis and treatment strategies.

scholarly journals Recent Developments in Targeting RAS Downstream Effectors for RAS-Driven Cancer Therapy

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7561
Author(s):  
Ozge Tatli ◽  
Gizem Dinler Doganay
Keyword(s):  
Cancer Therapy ◽  
Treatment Strategies ◽  
Pi3k Pathway ◽  
Compensatory Mechanisms ◽  
Downstream Signaling ◽  
Downstream Effector ◽  
Downstream Effectors ◽  
Frontline Treatment ◽  
Recent Developments ◽  
Sarcoma Virus

Aberrant activity of oncogenic rat sarcoma virus (RAS) protein promotes tumor growth and progression. RAS-driven cancers comprise more than 30% of all human cancers and are refractory to frontline treatment strategies. Since direct targeting of RAS has proven challenging, efforts have been centered on the exploration of inhibitors for RAS downstream effector kinases. Two major RAS downstream signaling pathways, including the Raf/MEK/Erk cascade and the phosphatidylinositol-3-kinase (PI3K) pathway, have become compelling targets for RAS-driven cancer therapy. However, the main drawback in the blockade of a single RAS effector is the multiple levels of crosstalk and compensatory mechanisms between these two pathways that contribute to drug resistance against monotherapies. A growing body of evidence reveals that the sequential or synergistic inhibition of multiple RAS effectors is a more convenient route for the efficacy of cancer therapy. Herein, we revisit the recent developments and discuss the most promising modalities targeting canonical RAS downstream effectors for the treatment of RAS-driven cancers.

scholarly journals The Landscape of Interactions between Hypoxia-Inducible Factors and Reactive Oxygen Species in the Gastrointestinal Tract

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yirui Shao ◽  
Kexing Wang ◽  
Xia Xiong ◽  
Hongnan Liu ◽  
Jian Zhou ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Gastrointestinal Tract ◽  
Oxygen Tension ◽  
Reactive Oxygen ◽  
Gastrointestinal Diseases ◽  
Oxygen Species ◽  
Hypoxia Inducible Factors ◽  
Oxidative Stresses ◽  
Major Organ ◽  
Cellular Oxygen

The gastrointestinal tract (GT) is the major organ involved in digestion, absorption, and immunity, which is prone to oxidative destruction by high levels of reactive oxygen species (ROS) from luminal oxidants, such as food, drugs, and pathogens. Excessive ROS will lead to oxidative stresses and disrupt essential biomolecules, which also act as cellular signaling molecules in response to growth factors, hormones, and oxygen tension changes. Hypoxia-inducible factors (HIFs) are critical regulators mediating responses to cellular oxygen tension changes, which are also involved in energy metabolism, immunity, renewal, and microbial homeostasis in the GT. This review discusses interactions between HIF (mainly HIF-1α) and ROS and relevant diseases in the GT combined with our lab’s work. It might help to develop new therapies for gastrointestinal diseases associated with ROS and HIF-1α.

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