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Reactive oxygen species,endothelial damage

Speranza Rubattu, Sebastiano Sciarretta, Simona Marchitti, Franca Bianchi, Maurizio Forte, Massimo Volpe
Atrial natriuretic peptide (ANP) is a cardiac hormone which plays important functions to maintain cardio-renal homeostasis. The peptide structure is highly conserved among species. However, a few gene variants are known to fall within the human ANP gene. The variant rs5065 (T2238C) exerts the most substantial effects. The T to C transition at the 2238 position of the gene (13-23% allele frequency in the general population) leads to the production of a 30-, instead of 28-, amino-acid-long α-carboxy-terminal peptide...
February 11, 2018: International Journal of Molecular Sciences
Orrette R Wauchope, Michelle M Mitchener, William N Beavers, James J Galligan, Jeannie M Camarillo, William D Sanders, Philip J Kingsley, Ha-Na Shim, Thomas Blackwell, Thong Luong, Mark deCaestecker, Joshua P Fessel, Lawrence J Marnett
Reactive oxygen species (ROS) are formed in mitochondria during electron transport and energy generation. Elevated levels of ROS lead to increased amounts of mitochondrial DNA (mtDNA) damage. We report that levels of M1dG, a major endogenous peroxidation-derived DNA adduct, are 50-100-fold higher in mtDNA than in nuclear DNA in several different human cell lines. Treatment of cells with agents that either increase or decrease mitochondrial superoxide levels leads to increased or decreased levels of M1dG in mtDNA, respectively...
February 9, 2018: Nucleic Acids Research
Cui Ma, Andreas M Beyer, Matthew Durand, Anne V Clough, Daling Zhu, Laura Norwood Toro, Maia Terashvili, Johnathan D Ebben, R Blake Hill, Said H Audi, Meetha Medhora, Elizabeth R Jacobs
OBJECTIVE: We explored mechanisms that alter mitochondrial structure and function in pulmonary endothelial cells (PEC) function after hyperoxia. APPROACH AND RESULTS: Mitochondrial structures of PECs exposed to hyperoxia or normoxia were visualized and mitochondrial fragmentation quantified. Expression of pro-fission or fusion proteins or autophagy-related proteins were assessed by Western blot. Mitochondrial oxidative state was determined using mito-roGFP. Tetramethylrhodamine methyl ester estimated mitochondrial polarization in treatment groups...
February 1, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Danize A Rizzetti, Taiz M da Silva, Alyne G Escobar, Janaina Piagette, Franck M Peçanha, Dalton V Vassallo, Maria J Alonso, Mercedes Salaices, Giulia A Wiggers
Low doses of mercury (Hg) promote deleterious effects on cardiovascular system, but the mechanisms implicated remain unclear. This study analyzed whether angiotensin II AT-1 receptors are involved in the vascular dysfunction caused by chronic exposure to low HgCl2 doses. For this, rats were divided into four groups and untreated (saline by im injections and tap water by gavage) or treated for 30 days as follows: Mercury (HgCl2im, first dose of 4.6 µg kg-1 and subsequent doses of 0.07 µg kg-1 day-1, and tap water by gavage); Losartan (saline im and losartan, 15 mg kg-1 day-1, by gavage); Losartan-Mercury (HgCl2im and Losartan by gavage)...
January 29, 2018: Environmental Research
Akiko Sekiguchi, Sei-Ichiro Motegi, Akihiko Uchiyama, Akihito Uehara, Chisako Fujiwara, Sahori Yamazaki, Buddhini Perera, Hideharu Nakamura, Sachiko Ogino, Yoko Yokoyama, Ryoko Akai, Takao Iwawaki, Osamu Ishikawa
BACKGROUND: We previously identified that botulinum toxin A (BTX-A) suppressed pressure ulcer (PU) formation after cutaneous ischemia-reperfusion (I/R) injury; however, regulation of cutaneous I/R-induced oxidative and endoplasmic reticulum (ER) stress by BTX-B was not investigated. Additionally, the efficacy of BTX-B injection has never been examined. OBJECTIVE: Objective was to assess the effects of BTX-B on the formation of PU by cutaneous I/R injury, and the regulation of oxidative and ER stress in I/R injury by BTX-B...
February 2, 2018: Journal of Dermatological Science
Weiwei Cai, Zhenpeng Zhang, Yiqi Huang, Haijian Sun, Liying Qiu
The kidney is an important organ in the regulation of blood pressure, and it is also one of the primary target organs of hypertension. Kidney damage in response to hypertension eventually leads to renal insufficiency. The authors previously demonstrated that vaccarin exhibits a protective role in endothelial injury. However, the effects of vaccarin on the two-kidney, one clip (2K1C) renovascular hypertension model and subsequent kidney injury have yet to be fully elucidated. The present study was designed to investigate the roles and mechanisms of vaccarin in attenuating hypertension and whether vaccarin had beneficial effects on kidney injury...
January 2018: Experimental and Therapeutic Medicine
Yong Zhang, Xiaoqiang Yang, Chuan Qiu, Fei Liu, Peng Liu, Zhongwei Liu
Diabetes is characterized by a high level of advanced glycation end products (AGEs), which induce damage in the arterial endothelium. Matrine has been shown to have cardioprotective effects. This study's aim was to investigate the protective effects and possible molecular mechanisms of matrine in AGE-induced human aortic endothelial cell (HAEC) injury. Cultured HAECs were treated with AGEs and/or serially diluted matrine. Cell viability was evaluated by MTT assay. Intracellular reactive oxygen species production was determined by flow cytometry...
January 25, 2018: European Journal of Pharmacology
Ramon Alfonso Exeni, Romina Jimena Fernandez-Brando, Adriana Patricia Santiago, Gabriela Alejandra Fiorentino, Andrea Mariana Exeni, Maria Victoria Ramos, Marina Sandra Palermo
Hemolytic uremic syndrome (HUS) is defined as a triad of noninmune microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. The most frequent presentation is secondary to Shiga toxin (Stx)-producing Escherichia coli (STEC) infections, which is termed postdiarrheal, epidemiologic or Stx-HUS, considering that Stx is the necessary etiological factor. After ingestion, STEC colonize the intestine and produce Stx, which translocates across the intestinal epithelium. Once Stx enters the bloodstream, it interacts with renal endothelial and epithelial cells, and leukocytes...
January 25, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Di Lu, Wei Wang, Jingfeng Liu, Ling Qi, Runzhou Zhuang, Jianyong Zhuo, Xuanyu Zhang, Xiao Xu, Shusen Zheng
Peroxiredoxins (Prxs) belong to the superfamily of thiol-dependent peroxidases, and remove reactive oxygen species (ROS) and other oxidative stress products. The expression and activity of Prxs can be substantially affected by stimuli from the microenvironment, and in turn regulate cytokine secretion in the context of inflammation in both peroxidase-dependent and -independent pathways. Prxs translocate to mitochondria and are hyperoxidized during acute liver damage, and attenuate intracellular ROS accumulation through their peroxidase activity...
January 19, 2018: Food and Chemical Toxicology
Binoy Appukuttan, Yuefang Ma, Andrew Stempel, Liam M Ashander, Devy Deliyanti, Jennifer L Wilkinson-Berka, Justine R Smith
BACKGROUND: Over-production of reactive oxygen species (ROS) and resulting oxidative stress contribute to retinal damage in vascular diseases that include diabetic retinopathy, retinopathy of prematurity and major retinal vessel occlusions. NADPH oxidase (Nox) proteins are professional ROS-generating enzymes, and therapeutic targeting in these diseases has strong appeal. Pharmacological inhibition of Nox4 reduces the severity of experimental retinal vasculopathy. We investigated the potential application of this drug approach in humans...
January 23, 2018: Clinical & Experimental Ophthalmology
Chen Fu, Baoxin Chen, Xianglan Jin, Xuemei Liu, Fengli Wang, Rongjuan Guo, Zhigang Chen, Hong Zheng, Le Wang, Yunling Zhang
Endothelial progenitor cell (EPC) dysfunction is associated with the formation of carotid atherosclerosis. It has been demonstrated that angiotensin II (Ang II) may impair the function of EPCs and puerarin, a natural product, possesses cardiovascular protective effects against oxidative stress and inflammation. Therefore, the present study aimed to investigate the beneficial effects of puerarin in Ang II‑induced EPC injury, and to elucidate the underlying mechanisms. Treatment with Ang II suppressed EPC proliferation and migration, increased the expression of the senescence marker β‑galactosidase, and the adhesion molecules intracellular adhesion molecule‑1 and vascular cell adhesion molecule‑1...
December 19, 2017: Molecular Medicine Reports
Ryoko Tsukahara, Hisao Haniu, Yoshikazu Matsuda, Tamotsu Tsukahara
Alkyl-glycerophosphate (AGP) accumulates in atherogenic oxidized-LDL and human atherosclerotic plaques and is a potent agonist of peroxisome-proliferator-activated receptor-gamma (PPARγ). Recent studies suggest a potential regulatory role for PPARγ in endothelial nitric oxide synthase (eNOS) expression/activation and nitrogen oxide (NO) generation in the vascular endothelium. Importantly, eNOS-induced NO and advanced glycation end-products (AGEs) are involved in blood-vessel damage, and diabetic patients exhibit high serum NO and AGE levels; however, the effect of AGP on NO- and AGE-mediated endothelium dysfunction remains unknown...
January 18, 2018: Molecular and Cellular Endocrinology
S Portal-Núñez, J A Ardura, D Lozano, I Martínez de Toda, M De la Fuente, G Herrero-Beaumont, R Largo, P Esbrit
OBJECTIVES: Oxidative stress plays a major role in the onset and progression of involutional osteoporosis. However, classical antioxidants fail to restore osteoblast function. Interestingly, the bone anabolism of parathyroid hormone (PTH) has been shown to be associated with its ability to counteract oxidative stress in osteoblasts. The PTH counterpart in bone, which is the PTH-related protein (PTHrP), displays osteogenic actions through both its N-terminal PTH-like region and the C-terminal domain...
January 2018: Bone & Joint Research
J Trent Magruder, Joshua C Grimm, Todd C Crawford, Laura Johnston, Lakshmi Santhanam, R Scott Stephens, Dan E Berkowitz, Ashish S Shah, Errol L Bush, Mahendra Damarla, Rachel L Damico, Paul M Hassoun, Bo S Kim
BACKGROUND: Ischemia-reperfusion injury is characterized by an increase in oxidative stress and leads to significant morbidity and death. The tyrosine kinase c-Abl is activated by oxidative stress and mediates processes that affect endothelial barrier function. We hypothesized treatment with the c-Abl inhibitor imatinib would be protective against ischemia-reperfusion injury in our ex vivo rabbit model. METHODS: Heart-lung blocs were harvested from rabbits and stored in cold in Perfadex (Vitrolife, Englewood, CO) for 18 hours...
March 2018: Annals of Thoracic Surgery
Chenggui Wang, Cong Mao, Yiting Lou, Jianxiang Xu, Qingqing Wang, Zengjie Zhang, Qian Tang, Xiaolei Zhang, Huazi Xu, Yongzeng Feng
Attenuating oxidative stress-induced damage and promoting endothelial progenitor cell (EPC) differentiation are critical for ischaemic injuries. We suggested monotropein (Mtp), a bioactive constituent used in traditional Chinese medicine, can inhibit oxidative stress-induced mitochondrial dysfunction and stimulate bone marrow-derived EPC (BM-EPC) differentiation. Results showed Mtp significantly elevated migration and tube formation of BM-EPCs and prevented tert-butyl hydroperoxide (TBHP)-induced programmed cell death through apoptosis and autophagy by reducing intracellular reactive oxygen species release and restoring mitochondrial membrane potential, which may be mediated viamTOR/p70S6K/4EBP1 and AMPK phosphorylation...
December 26, 2017: Journal of Cellular and Molecular Medicine
Saeed Fadal Alrashdi, Devy Deliyanti, Dean Michael Talia, Jennifer Louise Wilkinson-Berka
Although increasing evidence indicates that endothelin-2 (Edn2) has distinct roles in tissue pathology including inflammation, glial cell dysfunction, and angiogenesis, its role in the retina and the factors that regulate its actions are not fully understood. We hypothesized that Edn2 damages the blood-retinal barrier (BRB) and this is mediated by interactions with the renin-angiotensin aldosterone system and reactive oxygen species derived from NADPH oxidase (Nox). C57BL/6J mice received an intravitreal injection of Edn2 or control vehicle to examine the blood pressure-independent effects of Edn2...
December 14, 2017: American Journal of Pathology
Yujing Zhang, Jian Huang, Xinglin Yang, Xiaofei Sun, Qincheng Xu, Baokui Wang, Peng Zhong, Zixiu Wei
BACKGROUND: Coronary atherosclerotic heart disease (CAD) is mainly caused by atherosclerosis, an inflammatory disease characterized by plaque formation in arteries. Reactive oxygen species caused structural damage and dysfunction of arterial endothelial cells. Thioredoxin-interacting protein (TXNIP) is the endogenous inhibitor and regulator of thioredoxin, a major cellular antioxidant and antiapoptotic system. In order to explore the role of TXNIP in the occurrence and development of CAD, we detected the TXNIP expression and discussed its molecular mechanisms in CAD...
December 2017: Medicine (Baltimore)
A R T Machado, A F Aissa, D L Ribeiro, L C Hernandes, C S Machado, M L P Bianchi, S V Sampaio, L M G Antunes
Colorectal carcinoma is one of the most common cancers in adults. As chemotherapy, the first-choice treatment for colorectal carcinoma, is often infeasible due to acquired tumor resistance and several adverse effects. It is important to discover and explore new molecules with better therapeutic action. Snake venom toxins have shown promising results with high cytotoxicity against tumor cells, but their mechanisms of action remain unclear. Here we examined how BjussuLAAO-II, an L-amino acid oxidase isolated from Bothrops jararacussu snake venom, exerts cytotoxicity towards colorectal adenocarcinoma human cells (Caco-2) and in human umbilical vein endothelial cell line (HUVEC)...
December 5, 2017: International Journal of Biological Macromolecules
Chunlan Fan, Yuan Qiao, Minke Tang
The aim of this study was to examine whether Notoginsenoside R1 (NR1) attenuates high glucose-induced cell damage in rat retinal capillary endothelial cells (RCECs) and to explore the mechanisms involved. The exposure of rat RCECs to high concentration of glucose (30 mM) for 72 h led to significant cytotoxicity, including decreased cell viability, reduced mitochondrial DNA copy number, increased lactate dehydrogenase release and elevated apoptosis. NR1, when present in the culture medium, markedly attenuated the high glucose-induced cytotoxicity in rat RCECs...
2017: Drug Design, Development and Therapy
Yanmei Cao, Cuicui Gu, Fangli Zhao, Yuanlin Tang, Xiaobing Cui, Le Shi, Li Xu, Lian Yin
Background: Cyathula officinalis Kuan is widely used in the clinics for the treatment of blood stasis in China. Objective: To evaluate the improving blood rheology and anti-inflammatory properties of C. officinalis Kuan extract (CO) and its active fraction (ACO) on acute blood stasis model Wistar rats and characterize the correlative constituents. Materials and Methods: CO at 0.26, 0.53, and 1.04 g/kg and ACO at 0.38, 0.75, and 1.5 g/kg were administered to acute blood stasis model Wistar rats for 3 days...
October 2017: Pharmacognosy Magazine
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