Endothelial STAT3 plays a critical role in generalized myocardial proinflammatory and proapoptotic signaling

2007 ◽  
Vol 293 (4) ◽  
pp. H2101-H2108 ◽  
Author(s):  
Meijing Wang ◽  
Wenjun Zhang ◽  
Paul Crisostomo ◽  
Troy Markel ◽  
Kirstan K. Meldrum ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cell ◽  
Myocardial Function ◽  
Critical Role ◽  
Caspase 8 ◽  
Biological Processes ◽  
Signal Transducer ◽  
Wild Type ◽  
Mapk Activation ◽  
Isolated Hearts

Signal transducer and activator of transcription (STAT) 3 is involved in mediating a broad range of biological processes, including cell survival, proliferation, and immune response. Recent evidence has indicated that STAT3 in cardiomyocytes can be activated by ischemic-oxidative stress and exerts cardioprotection in the ischemic heart. There is no information, however, regarding the effect of endothelial cell-derived STAT3 on the myocardial response to ischemiareperfusion (I/R) injury. We hypothesized that the ablation of the STAT3 gene in endothelial cells would worsen postischemic myocardial function by affecting capillary network integrity, suppressing antiapoptotic signaling. Isolated hearts from wild-type and endothelial cell STAT3 knockout (STAT3KO) mice were subjected to 20 min of global ischemia followed by 60 min of reperfusion. Endothelial cell STAT3 deficiency decreased recovery of myocardial function in response to I/R, which was associated with higher levels of LDH release, decreased activation of myocardial STAT3, and elevated p38 MAPK activation in STAT3 endothelial knockout (KO) hearts. In addition, although no significant apoptosis was observed in wild-type and KO hearts, our results showed more expression of myocardial caspase-8 and more apoptosis in the myocardium around the capillary in STAT3KO mice subjected to I/R. Furthermore, endothelial cell STAT3 ablation resulted in increased myocardial expression of IL-6 and suppressor of cytokine signal 3. This study demonstrates that endothelial cell-derived STAT3 plays an important role in postischemic myocardial function.

scholarly journals Recent Progress in the Study of Peroxiredoxin in the Harmful Algal Bloom Species Chattonella marina

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 162
Author(s):  
Yohei Shimasaki ◽  
Koki Mukai ◽  
Yuki Takai ◽  
Xuchun Qiu ◽  
Yuji Oshima
Keyword(s):  
Oxidative Stress ◽  
Growth Phase ◽  
Critical Role ◽  
High Irradiance ◽  
Growth Potential ◽  
Exponential Growth Phase ◽  
Wild Type ◽  
Chattonella Marina ◽  
Strong Light ◽  
Expression Strain

Peroxiredoxin (Prx) is a relatively recently discovered antioxidant enzyme family that scavenges peroxides and is known to be present in organisms from biological taxa ranging from bacteria to multicellular eukaryotes, including photosynthetic organisms. Although there have been many studies of the Prx family in higher plants, green algae, and cyanobacteria, few studies have concerned raphidophytes and dinoflagellates, which are among the eukaryotic algae that cause harmful algal blooms (HABs). In our proteomic study using 2-D electrophoresis, we found a highly expressed 2-Cys peroxiredoxin (2-CysPrx) in the raphidophyte Chattonella marina var. antiqua, a species that induces mass mortality of aquacultured fish. The abundance of the C. marina 2-CysPrx enzyme was highest in the exponential growth phase, during which photosynthetic activity was high, and it then decreased by about a factor of two during the late stationary growth phase. This pattern suggested that 2-CysPrx is a key enzyme involved in the maintenance of high photosynthesis activity. In addition, the fact that the depression of photosynthesis by excessively high irradiance was more severe in the 2-CysPrx low-expression strain (wild type) than in the normal-expression strain (wild type) of C. marina suggested that 2-CysPrx played a critical role in protecting the cell from oxidative stress caused by exposure to excessively high irradiance. In the field of HAB research, estimates of growth potential have been desired to predict the population dynamics of HABs for mitigating damage to fisheries. Therefore, omics approaches have recently begun to be applied to elucidate the physiology of the growth of HAB species. In this review, we describe the progress we have made using a molecular physiological approach to identify the roles of 2-CysPrx and other antioxidant enzymes in mitigating environmental stress associated with strong light and high temperatures and resultant oxidative stress. We also describe results of a survey of expressed Prx genes and their growth-phase-dependent behavior in C. marina using RNA-seq analysis. Finally, we speculate about the function of these genes and the ecological significance of 2-CysPrx, such as its involvement in circadian rhythms and the toxicity of C. marina to fish.

scholarly journals The YAP1 Homolog–Mediated Oxidative Stress Tolerance Is Crucial for Pathogenicity of the Necrotrophic Fungus Alternaria alternata in Citrus

2009 ◽  
Vol 22 (8) ◽  
pp. 942-952 ◽  
Author(s):  
Ching-Hsuan Lin ◽  
Siwy Ling Yang ◽  
Kuang-Ren Chung
Keyword(s):  
Oxidative Stress ◽  
Alternaria Alternata ◽  
Critical Role ◽  
Disease Process ◽  
Brown Spot ◽  
Null Mutant ◽  
Wild Type ◽  
Protein Fusion ◽  
Fungal Pathogenicity

Citrus brown spot disease is caused by the necrotrophic fungus Alternaria alternata. Its pathogenic capability has been thought to depend exclusively on the production of host-selective ACT toxin. However, circumvention of plant defenses is also likely to be important for the disease process. To investigate the fungal response to host-generated reactive oxygen species (ROS), we cloned and characterized the AaAP1 gene of A. alternata, which encodes a polypeptide resembling yeast YAP1-like transcriptional activators implicated in cellular responses to stress. Expression of the AaAP1 gene in a wild-type strain was primarily induced by H2O2 or ROS-generating oxidants. Using a loss-of-function mutation in the AaAP1 gene, we demonstrated an essential requirement for oxidative tolerance during the host invasion step. Mutants lacking AaAP1 showed increased sensitivity to H2O2 and loss of fungal pathogenicity. The ΔAaAP1 null mutant did not cause any visible necrotic lesions on wounded or unwounded leaves of citrus cv. Minneola. Compared with the wild type, the null mutant displayed lower catalase, peroxidase, and superoxide dismutase activities. All mutant phenotypes were restored to the wild type in fungal strains expressing a functional copy of AaAP1. Upon exposure to H2O2, the AaAP1::sGFP (synthetic green fluorescent protein) fusion protein became localized in the nucleus. Inoculation of the mutant with NADPH oxidase inhibitors partially restored fungal pathogenicity. Our results highlight the global regulatory role of a YAP1 homolog in response to oxidative stress in A. alternata and provide insights into the critical role of ROS detoxification in the pathogenicity of A. alternata.

scholarly journals Redox-Dependent Structural Modification of Nucleoredoxin Triggers Defense Responses against Alternaria brassicicola in Arabidopsis

2020 ◽  
Vol 21 (23) ◽  
pp. 9196
Author(s):  
Chang Ho Kang ◽  
Joung Hun Park ◽  
Eun Seon Lee ◽  
Seol Ki Paeng ◽  
Ho Byoung Chae ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Structural Modification ◽  
Quantitative Polymerase Chain Reaction ◽  
Defense Responses ◽  
Alternaria Brassicicola ◽  
Low Molecular Weight ◽  
Biological Processes ◽  
Wild Type ◽  
Molecular Sensor ◽  
Polymerase Chain

In plants, thioredoxin (TRX) family proteins participate in various biological processes by regulating the oxidative stress response. However, their role in phytohormone signaling remains largely unknown. In this study, we investigated the functions of TRX proteins in Arabidopsis thaliana. Quantitative polymerase chain reaction (qPCR) experiments revealed that the expression of ARABIDOPSIS NUCLEOREDOXIN 1 (AtNRX1) is specifically induced by the application of jasmonic acid (JA) and upon inoculation with a necrotrophic fungal pathogen, Alternaria brassicicola. The AtNRX1 protein usually exists as a low molecular weight (LMW) monomer and functions as a reductase, but under oxidative stress AtNRX1 transforms into polymeric forms. However, the AtNRX1M3 mutant protein, harboring four cysteine-to-serine substitutions in the TRX domain, did not show structural modification under oxidative stress. The Arabidopsisatnrx1 null mutant showed greater resistance to A. brassicicola than wild-type plants. In addition, plants overexpressing both AtNRX1 and AtNRX1M3 were susceptible to A. brassicicola infection. Together, these findings suggest that AtNRX1 normally suppresses the expression of defense-responsive genes, as if it were a safety pin, but functions as a molecular sensor through its redox-dependent structural modification to induce disease resistance in plants.

scholarly journals Oxidative Stress: Role and Response of Short Guanine Tracts at Genomic Locations

2019 ◽  
Vol 20 (17) ◽  
pp. 4258 ◽  
Author(s):  
Singh ◽  
Kukreti ◽  
Saso ◽  
Kukreti
Keyword(s):  
Oxidative Stress ◽  
Small Molecules ◽  
Critical Role ◽  
Biological Processes ◽  
Telomere Shortening ◽  
Genome Damage ◽  
G Quadruplex ◽  
Self Association ◽  
Genomic Locations ◽  
Lifestyle Related Diseases

Over the decades, oxidative stress has emerged as a major concern to biological researchers. It is involved in the pathogenesis of various lifestyle-related diseases such as hypertension, diabetes, atherosclerosis, and neurodegenerative diseases. The connection between oxidative stress and telomere shortening via oxidative guanine lesion is well documented. Telomeres are confined to guanine rich ends of chromosomes. Owing to its self-association properties, it adopts G-quadruplex structures and hampers the overexpression of telomerase in the cancer cells. Guanine, being the most oxidation prone nucleobase, when structured in G-quadruplex entity, is found to respond peculiarly towards oxidative stress. Interestingly, this non-Watson–Crick structural feature exists abundantly in promoters of various oncogenes, exons and other genomic locations. The involvement of G-quadruplex architecture in oncogene promoters is well recognized in gene regulation processes. Development of small molecules aimed to target G-quadruplex structures, have found to alter the overexpression of oncogenes. The interaction may lead to the obstruction of diseased cell having elevated level of reactive oxygen species (ROS). Thus, presence of short guanine tracts (Gn) forming G-quadruplexes suggests its critical role in oxidative genome damage. Present review is a modest attempt to gain insight on the association of oxidative stress and G-quadruplexes, in various biological processes.

scholarly journals Progerin Expression Induces Inflammation, Oxidative Stress and Senescence in Human Coronary Endothelial Cells

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1201 ◽  
Author(s):  
Guillaume Bidault ◽  
Marie Garcia ◽  
Jacqueline Capeau ◽  
Romain Morichon ◽  
Corinne Vigouroux ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Premature Aging ◽  
Lamin A ◽  
Wild Type ◽  
Human Endothelial Cells ◽  
Endothelial Cell Function ◽  
Age Related

Hutchinson–Gilford progeria syndrome (HGPS) is a rare premature aging disorder notably characterized by precocious and deadly atherosclerosis. Almost 90% of HGPS patients carry a LMNA p.G608G splice variant that leads to the expression of a permanently farnesylated abnormal form of prelamin-A, referred to as progerin. Endothelial dysfunction is a key determinant of atherosclerosis, notably during aging. Previous studies have shown that progerin accumulates in HGPS patients’ endothelial cells but also during vascular physiological aging. However, whether progerin expression in human endothelial cells can recapitulate features of endothelial dysfunction is currently unknown. Herein, we evaluated the direct impact of exogenously expressed progerin and wild-type lamin-A on human endothelial cell function and senescence. Our data demonstrate that progerin, but not wild-type lamin-A, overexpression induces endothelial cell dysfunction, characterized by increased inflammation and oxidative stress together with persistent DNA damage, increased cell cycle arrest protein expression and cellular senescence. Inhibition of progerin prenylation using a pravastatin–zoledronate combination partly prevents these defects. Our data suggest a direct proatherogenic role of progerin in human endothelial cells, which could contribute to HGPS-associated early atherosclerosis and also potentially be involved in physiological endothelial aging participating to age-related cardiometabolic diseases.

scholarly journals Scavenging superoxide selectively in mouse forebrain is associated with improved cardiac function and survival following myocardial infarction

2009 ◽  
Vol 296 (1) ◽  
pp. R1-R8 ◽  
Author(s):  
Timothy E. Lindley ◽  
David W. Infanger ◽  
Mark Rishniw ◽  
Yi Zhou ◽  
Marc F. Doobay ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Central Nervous System ◽  
Nervous System ◽  
Gene Transfer ◽  
Cardiac Function ◽  
Myocardial Function ◽  
Critical Role ◽  
Coronary Artery Ligation ◽  
Control Vector

Dysregulation in central nervous system (CNS) signaling that results in chronic sympathetic hyperactivity is now recognized to play a critical role in the pathogenesis of heart failure (HF) following myocardial infarction (MI). We recently demonstrated that adenovirus-mediated gene transfer of cytoplasmic superoxide dismutase (Ad-Cu/ZnSOD) to forebrain circumventricular organs, unique sensory structures that lack a blood-brain barrier and link peripheral blood-borne signals to central nervous system cardiovascular circuits, inhibits both the MI-induced activation of these central signaling pathways and the accompanying sympathoexcitation. Here, we tested the hypothesis that this forebrain-targeted reduction in oxidative stress translates into amelioration of the post-MI decline in myocardial function and increase in mortality. Adult C57BL/6 mice underwent left coronary artery ligation or sham surgery along with forebrain-targeted gene transfer of Ad-Cu/ZnSOD or a control vector. The results demonstrate marked MI-induced increases in superoxide radical formation in one of these forebrain regions, the subfornical organ (SFO). Ad-Cu/ZnSOD targeted to this region abolished the increased superoxide levels and led to significantly improved myocardial function compared with control vector-treated mice. This was accompanied by diminished levels of cardiomyocyte apoptosis in the Ad-Cu/ZnSOD but not the control vector-treated group. These effects of superoxide scavenging with Ad-Cu/ZnSOD in the forebrain paralleled increased post-MI survival rates compared with controls. This suggests that oxidative stress in the SFO plays a critical role in the deterioration of cardiac function following MI and underscores the promise of CNS-targeted antioxidant therapy for the treatment of MI-induced HF.

scholarly journals The Ccr4-Not Complex Regulates Skn7 through Srb10 Kinase

2007 ◽  
Vol 6 (12) ◽  
pp. 2251-2259 ◽  
Author(s):  
Eve Lenssen ◽  
Nowel Azzouz ◽  
Agnès Michel ◽  
Emilie Landrieux ◽  
Martine A. Collart
Keyword(s):  
Oxidative Stress ◽  
Saccharomyces Cerevisiae ◽  
Critical Role ◽  
Mrna Degradation ◽  
Dependent Manner ◽  
Wild Type ◽  
Cellular Events ◽  
Protein Ubiquitination ◽  
And Oxidative Stress ◽  
Two Hybrid

ABSTRACT The Ccr4-Not complex is a multifunctional regulatory platform composed of nine subunits that controls diverse cellular events including mRNA degradation, protein ubiquitination, and transcription. In this study, we identified the yeast Saccharomyces cerevisiae osmotic and oxidative stress transcription factor Skn7 as a new target for regulation by the Ccr4-Not complex. Skn7 interacts with Not1 in a two-hybrid assay and coimmunoprecipitates with Not5 in a Not4-dependent manner. Skn7-dependent expression of OCH1 and Skn7 binding to the OCH1 promoter are increased in not4Δ or not5Δ mutants. Skn7 purified from wild-type cells but not from not4Δ cells is associated with the Srb10 kinase. This kinase plays a central role in the regulation of Skn7 by Not4, since increased OCH1 expression in not4Δ cells requires Srb10. These results reveal a critical role for the Ccr4-Not complex in the mechanism of activation of Skn7 that is dependent upon the Srb10 kinase.

scholarly journals Critical Role ofl-Arginine in Endothelial Cell Survival During Oxidative Stress

Circulation ◽  
2003 ◽  
Vol 107 (20) ◽  
pp. 2607-2614 ◽  
Author(s):  
Christoph V. Suschek ◽  
Oliver Schnorr ◽  
Karsten Hemmrich ◽  
Olivier Aust ◽  
Lars-Oliver Klotz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cell ◽  
Cell Survival ◽  
Critical Role ◽  
Endothelial Cell Survival

scholarly journals Regulation of fibrinolysis by S100A10 in vivo

Blood ◽  
2011 ◽  
Vol 118 (11) ◽  
pp. 3172-3181 ◽  
Author(s):  
Alexi P. Surette ◽  
Patricia A. Madureira ◽  
Kyle D. Phipps ◽  
Victoria A. Miller ◽  
Per Svenningsson ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Function ◽  
Blood Clot ◽  
Critical Role ◽  
Receptor Protein ◽  
Null Mouse ◽  
Wild Type ◽  
Endothelial Cell Function

AbstractEndothelial cells form the inner lining of vascular networks and maintain blood fluidity by inhibiting blood coagulation and promoting blood clot dissolution (fibrinolysis). Plasmin, the primary fibrinolytic enzyme, is generated by the cleavage of the plasma protein, plasminogen, by its activator, tissue plasminogen activator. This reaction is regulated by plasminogen receptors at the surface of the vascular endothelial cells. Previous studies have identified the plasminogen receptor protein S100A10 as a key regulator of plasmin generation by cancer cells and macrophages. Here we examine the role of S100A10 and its annexin A2 binding partner in endothelial cell function using a homozygous S100A10-null mouse. Compared with wild-type mice, S100A10-null mice displayed increased deposition of fibrin in the vasculature and reduced clearance of batroxobin-induced vascular thrombi, suggesting a role for S100A10 in fibrinolysis in vivo. Compared with wild-type cells, endothelial cells from S100A10-null mice demonstrated a 40% reduction in plasminogen binding and plasmin generation in vitro. Furthermore, S100A10-deficient endothelial cells demonstrated impaired neovascularization of Matrigel plugs in vivo, suggesting a role for S100A10 in angiogenesis. These results establish an important role for S100A10 in the regulation of fibrinolysis and angiogenesis in vivo, suggesting S100A10 plays a critical role in endothelial cell function.

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