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Jui-Hsiang Hung, Shi-Kae Wee, Hany A Omar, Chia-Hui Su, Hsing-Yi Chen, Pin-Shern Chen, Chien-Chih Chiu, Ming-Syuan Wu, Yen-Ni Teng
Leucine-rich repeats and WD repeat domain containing protein 1 (LRWD1) is implicated in the regulation of signal transduction, transcription, RNA processing and tumor development. However, LRWD1 transcriptional regulation is not fully understood. This study aimed to investigate the relationship between LRWD1 expression and reactive oxygen species (ROS) level in human embryonal carcinoma cell line, NT2/D1 cells, which will help in understanding the transcriptional regulatory role of ROS in cells. Results showed that the exposure of NT2/D1 cells to various concentrations of hydrogen peroxide (H2 O2 ) and the nitric oxide (NO) donor sodium nitroprusside (SNP) caused a significant increase in the mRNA and protein expression of LRWD1...
March 12, 2018: Biochimie
Katarzyna A Cieslik, Rajagopal V Sekhar, Alejandro Granillo, Anilkumar Reddy, Guillermo Medrano, Celia Pena Heredia, Mark L Entman, Dale J Hamilton, Shumin Li, Erin Reineke, Anisha A Gupte, Aijun Zhang, George E Taffet
Metabolic, inflammatory and functional changes occur in cardiovascular aging which may stem from oxidative stress and be remediable with antioxidants. Glutathione, an intracellular antioxidant, declines with aging, and supplementation with glutathione precursors, N-Acetyl Cysteine (NAC) and Glycine (Gly), increases tissue glutathione. Thirty month-old mice were fed diets supplemented with NAC or NAC+Gly and, after seven weeks, cardiac function and molecular studies were performed.The NAC+Gly supplementation improved diastolic function, increasing peak early filling velocity, and reducing relaxation time, left atrial volume, and left ventricle end diastolic pressure...
March 10, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
M Yasar, I Erdi, B Kaya
AIM: We investigated the effects of atorvastatin and N-acetyl cysteine in decreasing ischemia-reperfusion damage after detorsion of a volvulus of the cecum and ascending colon. METHODS: Wistar albino rats (250-300 g) were divided into four groups. A cecal-ascending colon volvulus was created by the intestinal clockwise 720° rotation. At the end of one hour, the bowel was detorsioned. Group I (n = 7) was the sham (laparotomy) group, Group II (n = 7) the control (no treatment, volvulus or detorsion), Group III (n = 7) (N-acetyl cysteine administered ) , and Group IV (n = 7) (atorvastatin administered ) group...
2018: Bratislavské Lekárske Listy
Helen Hernández, Alejandra Parra, Nicolas Tobar, Jessica Molina, Violeta Kallens, Miltha Hidalgo, Diego Varela, Jorge Martínez, Omar Porras
Aerobic metabolism brings inexorably the production of reactive oxygen species (ROS), which are counterbalanced by intrinsic antioxidant defenses avoiding deleterious intracellular effects. Redox balance is the resultant of metabolic functioning under environmental inputs (i.e. diet, pollution) and the activity of intrinsic antioxidant machinery. Monitoring of intracellular hydrogen peroxide has been successfully achieved by redox biosensor advent; however, to track the intrinsic disulfide bond reduction capacity represents a fundamental piece to understand better how redox homeostasis is maintained in living cells...
March 2, 2018: Redox Biology
Dávid Kókai, Tímea Mosolygó, Dezső P Virók, Valéria Endrész, Katalin Burián
PURPOSE: Within the community, 10 % of acquired pneumonia is caused by Chlamydia pneumoniae. N-acetyl-cysteine (NAC) is one of the most commonly used mucolytics in respiratory diseases, but its effect on C. pneumoniae infection has not yet been investigated. In this study, our aim was to investigate whether NAC influences the replication of C. pneumoniae. After determining that NAC does have an effect on C. pneumoniae replication, the effect of an alternative drug called Ambroxol (Ax) was investigated...
March 9, 2018: Journal of Medical Microbiology
Ri-Zhen Huang, Xiao-Chao Huang, Bin Zhang, Hai-Yang Jia, Zhi-Xin Liao, Heng-Shan Wang
BACKGROUND: Hepatocellular carcinoma (HCC) is the leading cause of cancer death, and novel chemotherapeutic drugs for treating HCC are urgently needed. 16-O-caffeoyl-16-hydroxylhexadecanoic acid (CHHA) is a new phenylpropanoid isolated by our group from Euphorbia nematocypha which is commonly used to treat solid tumors. However, the underlying mechanisms responsible for the CHHA-induced apoptosis in cancer cells, particularly in HCC, remain unknown. PURPOSE: In the present work, we evaluated the growth inhibitory effect of CHHA on HCC cells and explored the underlying molecular mechanisms...
March 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Wei Wu, Bao-Hua Liu, Cheng-Long Xie, Xiao-Dong Xia, Yan-Mei Zhang
N-acetyl cysteine (NAC) has been extensively reported to exert neuroprotective effects on the central nervous system. Oxidative stress may contribute to the underlying mechanisms causing Alzheimer's disease (AD). The effect of NAC against oxidative stress injury was investigated in a cellular model of AD in the present study and the underlying mechanisms were revealed. The neuroprotective action of NAC (1, 10, 100 and 1,000 µmol/l) on a cellular model of AD [hydrogen peroxide (H2O2)‑induced (3, 30 and 300 µmol/l) toxicity in primary rat hippocampus neurons] demonstrated the underlying mechanisms...
March 7, 2018: Molecular Medicine Reports
Esteban Luna, Samantha C Decker, Dawn M Riddle, Anna Caputo, Bin Zhang, Tracy Cole, Carrie Caswell, Sharon X Xie, Virginia M Y Lee, Kelvin C Luk
The accumulation of misfolded α-synuclein (aSyn) and neuron loss define several neurodegenerative disorders including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). However, the precise relationship between pathology and neurotoxicity and why these processes disproportionately affect certain neuron subpopulations are poorly understood. We show here that Math2-expressing neurons in the hippocampal Cornu ammonis (CA), a region significantly affected by aSyn pathology in advanced PD and DLB, are highly susceptible to pathological seeding with pre-formed fibrils (PFFs), in contrast to dentate gyrus neurons, which are relatively spared...
March 3, 2018: Acta Neuropathologica
Mohammed Kawser Hossain, Subbroto Kumar Saha, Ahmed Abdal Dayem, Jung-Hyun Kim, Kyeongseok Kim, Gwang-Mo Yang, Hye Yeon Choi, Ssang-Goo Cho
Influenza virus remains a major health concern worldwide, and there have been continuous efforts to develop effective antivirals despite the use of annual vaccination programs. The purpose of this study was to determine the anti-influenza activity of Bax inhibitor-1 ( BI-1 ). Madin-Darby Canine Kidney (MDCK) cells expressing wild type BI-1 and a non-functional BI-1 mutant, BI-1 ∆C (with the C-terminal 14 amino acids deleted) were prepared and infected with A/PR/8/34 influenza virus. BI-1 overexpression led to the suppression of virus-induced cell death and virus production compared to control Mock or BI-1 ∆C overexpression...
March 2, 2018: International Journal of Molecular Sciences
Su Eun Choi, Yun Sun Park, Hyun Chul Koh
Inflammation generated by environmental toxicants including pesticides could be one of the factors underlying neuronal cell damage in neurodegenerative diseases. In this study, we investigated the mechanisms by which inflammatory responses contribute to apoptosis in PC12 cells treated with diquat. We found that diquat induced apoptosis, as demonstrated by the activation of caspases and nuclear condensation, inhibition of mitochondrial complex I activity, and decreased ATP level in PC12 cells. Diquat also reduced the dopamine level, indicating that cell death induced by diquat is due to cytotoxicity of dopaminergic neuronal components in these cells...
February 27, 2018: Environmental Toxicology
Wei Zhu, Huilan Wang, Jianqin Wei, Gregory C Sartor, Michelle Meiqi Bao, Clay T Pierce, Claes R Wahlestedt, Derek M Dykxhoorn, Chunming Dong
Cocaine abuse increases the risk of cardiovascular mortality and morbidity; however, the underlying molecular mechanisms remain elusive. By using a mouse model for cocaine abuse/use, we found that repeated cocaine injection led to increased blood pressure and aortic stiffness in mice associated with elevated levels of reactive oxygen species (ROS) in the aortas, a phenomenon similar to that observed in hypertensive humans. This ROS elevation was correlated with downregulation of Me1 (malic enzyme 1), an important redox molecule that counteracts ROS generation, and upregulation of microRNA (miR)-30c-5p that targets Me1 expression by directly binding to its 3'UTR (untranslated region)...
February 26, 2018: Hypertension
Karla B Neves, Francisco J Rios, Lucas van der Mey, Rheure Alves-Lopes, Alan C Cameron, Massimo Volpe, Augusto C Montezano, Carmine Savoia, Rhian M Touyz
Although VEGF (vascular endothelial growth factor) inhibitors (VEGFIs), are effective anticancer therapies, they cause hypertension through unknown mechanisms. We questioned whether changes in vascular redox state may be important, because VEGF signaling involves nitric oxide (NO) and reactive oxygen species. Molecular mechanisms, including NOS, NADPH oxidase (Nox)-derived reactive oxygen species, antioxidant systems, and vasoconstrictor signaling pathways, were probed in human endothelial cells and vascular smooth muscle exposed to vatalanib, a VEGFI...
February 26, 2018: Hypertension
Shuyu Piao, Jun Wan Lee, Harsha Nagar, Saet-Byel Jung, Sujeong Choi, Seonhee Kim, Ikjun Lee, Sung-Min Kim, Nara Shin, Yu Ran Lee, Sang Do Lee, Jin Bong Park, Kaikobad Irani, Minho Won, Gang Min Hur, Byeong Hwa Jeon, Dong Woon Kim, Cuk-Seong Kim
AIMS: CR6 interacting factor 1 (CRIF1) deficiency impairs mitochondrial oxidative phosphorylation complexes, contributing to increased mitochondrial and cellular reactive oxygen species (ROS) production. CRIF1 downregulation has also been revealed to decrease sirtuin 1 (SIRT1) expression and impair vascular function. Inhibition of SIRT1 disturbs oxidative energy metabolism and stimulates nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-induced inflammation. Therefore, we hypothesized that both CRIF1 deficiency-induced mitochondrial ROS production and SIRT1 reduction play stimulatory roles in vascular inflammation...
2018: PloS One
Sanford P C Hsu, John S Kuo, Hsin-Chien Chiang, Hsin-Ell Wang, Yu-Shan Wang, Cheng-Chung Huang, Yi-Chun Huang, Mau-Shin Chi, Minesh P Mehta, Kwan-Hwa Chi
Glioblastoma (GBM) cells are characterized by high phagocytosis, lipogenesis, exocytosis activities, low autophagy capacity and high lysosomal demand are necessary for survival and invasion. The lysosome stands at the cross roads of lipid biosynthesis, transporting, sorting between exogenous and endogenous cholesterol. We hypothesized that three already approved drugs, the autophagy inducer, sirolimus (rapamycin, Rapa), the autophagy inhibitor, chloroquine (CQ), and DNA alkylating chemotherapy, temozolomide (TMZ) could synergize against GBM...
January 23, 2018: Oncotarget
Emmeran Le Moal, Gaëtan Juban, Anne Sophie Bernard, Tamas Varga, Clotilde Policar, Bénédicte Chazaud, Rémi Mounier
Macrophages are key players of immunity that display different functions according to their activation states. In a regenerative context, pro-inflammatory macrophages (Ly6Cpos ) are involved in the mounting of the inflammatory response whereas anti-inflammatory macrophages (Ly6Cneg ) dampen the inflammation and promote tissue repair. Reactive oxygen species (ROS) production is a hallmark of tissue injury and of subsequent inflammation as described in a bacterial challenge context. However, whether macrophages produce ROS following a sterile tissue injury is uncertain...
February 17, 2018: Free Radical Biology & Medicine
Qiao Wang, Xiuxiu Du, Ke Ma, Ping Shi, Wenbin Liu, Jing Sun, Min Peng, Zhiwei Huang
Elongases FEN1/ELO2 and SUR4/ELO3 are important enzymes involved in the elongation of long-chain fatty acids (LCFAs) to very long-chain fatty acids (VLCFAs) in Saccharomyces cerevisiae. The molecular mechanism of the involvement of these elongases in lipotoxicity is unclear. In the present study, we investigated the role of VLCFA elongases in oleic acid-mediated yeast cytotoxicity. The spot test showed that yeast strains with the deletion of ELO2 or ELO3 were strikingly sensitive to oleic acid, while there was no change on the growth of strain with deleted ELO1 which was involved in the elongation of C14 fatty acid (FA) to C16 FA...
March 2018: Microbiological Research
Jitender Kumar Bhardwaj, Priyanka Saraf, Priya Kumari, Meenu Mittal, Vijay Kumar
Toxicological studies so far suggest that excessive use of malathion, an organophosphate insecticide, causes serious ill-effects in mammalian reproductive physiology. The present study aims at assessing malathion-induced toxicity in a dose- and time-dependent manner with mitigating effects of N-acetyl-l-cysteine. The testicular germ cell viability was monitored using MTT assay, where NAC, being an antioxidant significantly reduced malathion-induced toxicity by enhancing the frequency of cell viability. The histomorphological analysis showed that NAC successfully diminished several apoptotic features in testicular cells, induced by malathion...
February 19, 2018: Journal of Biochemical and Molecular Toxicology
Kang Li, Yan Li, Jie Mi, Lu Mao, Xiuguo Han, Jie Zhao
Oxidative stress induced disc cell apoptosis plays an important role in intervertebral disc (IVD) degeneration. The present study aims to investigate effects of resveratrol (RV), a natural polyphenol compound, on sodium nitroprusside (SNP) induced nucleus pulposus (NP) cell apoptosis and related mechanism. Rat NP cells were pretreated with RV, N-acetyl cysteine (NAC) and carboxy-PTIO (PTIO) before SNP treatment. Cell Counting Kit-8 assay was carried out for cell viability evaluation. Annexin V/propidium iodide (PI), Hoechst 33258 and Actin‑Tracker Green and Tubulin-Tracker Red staining were conducted to detect NP cell apoptosis and apoptotic structural changes...
February 6, 2018: International Journal of Molecular Medicine
Xiya Zhang, Ying Wang, Tony Velkov, Shusheng Tang, Chongshan Dai
The molecular mechanisms of T-2 mycotoxin induced neurotoxicity remains enigmatic. In the present study we show that T-2 toxin induced neurotoxicity in mouse neuroblastoma2a (N2a) cells is both dose- and time-dependent and is associated with oxidative stress, mitochondrial dysfunction and apoptosis. T-2 toxin treatment of N2a cells at 10, 20, 40 and 80 ng/mL for 24 h significantly up-regulated the mRNA expression of p53, Bax, and caspase-8 and down-regulated the expression of Nrf2 and HO-1 mRNA and protein expression...
February 9, 2018: Food and Chemical Toxicology
Yan Zhou, Gaoxiang Yang, Hua Tian, Yabin Hu, Sai Wu, Yang Geng, Kai Lin, Wei Wu
Sulforaphane (SFN) inhibited growth in many cancers, but its half-life is 2 h in circulation. However, its metabolites, sulforaphane-cysteine (SFN-Cys) and sulforaphane-N-acetyl-cysteine (SFN-NAC) had longer half-lives and decreased the cell viability in both dose- and time-dependent manners in human prostate cancer. Flow cytometry assay revealed that these two SFN metabolites induced apoptosis with the features such as vacuolization, disappeared nuclear envelope, nuclear agglutination and fragmentation via transmission electron microscopy observation...
March 2018: Endocrine-related Cancer
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