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https://www.readbyqxmd.com/read/29150734/the-sirtuin-1-2-inhibitor-tenovin-1-induces-a-nonlinear-apoptosis-inducing-factor-dependent-cell-death-in-a-p53-null-ewing-s-sarcoma-cell-line
#1
Christian Marx, Lisa Marx-Blümel, Nora Lindig, René Thierbach, Doerte Hoelzer, Sabine Becker, Susan Wittig, Roland Lehmann, Hortense Slevogt, Thorsten Heinzel, Zhao-Qi Wang, James F Beck, Jürgen Sonnemann
The sirtuin 1/2 inhibitor tenovin-1 activates p53 and may have potential in the management of cancer. Here, we investigated the responsiveness of Ewing's sarcoma cells to tenovin-1. We examined its effects in two Ewing's sarcoma cell lines with different p53 status, i.e. in p53 wild-type and p53 null cells. Effects were assessed by flow cytometric analyses of cell death, mitochondrial membrane depolarization and reactive oxygen species (ROS) generation, by caspase 3/7 activity measurement, by mRNA expression profiling and by immunoblotting...
November 18, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29150633/ketamine-s-antidepressant-effect-is-mediated-by-energy-metabolism-and-antioxidant-defense-system
#2
Katja Weckmann, Michael J Deery, Julie A Howard, Renata Feret, John M Asara, Frederik Dethloff, Michaela D Filiou, Jamie Iannace, Christiana Labermaier, Giuseppina Maccarrone, Christian Webhofer, Larysa Teplytska, Kathryn Lilley, Marianne B Müller, Christoph W Turck
Fewer than 50% of all patients with major depressive disorder (MDD) treated with currently available antidepressants (ADs) show full remission. Moreover, about one third of the patients suffering from MDD does not respond to conventional ADs and develop treatment-resistant depression (TRD). Ketamine, a non-competitive, voltage-dependent N-Methyl-D-aspartate receptor (NMDAR) antagonist, has been shown to have a rapid antidepressant effect, especially in patients suffering from TRD. Hippocampi of ketamine-treated mice were analysed by metabolome and proteome profiling to delineate ketamine treatment-affected molecular pathways and biosignatures...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150332/organic-arsenicals-target-thioredoxin-reductase-followed-by-oxidative-stress-and-mitochondrial-dysfunction-resulting-in-apoptosis
#3
Xiao-Yang Fan, Yu-Jiao Liu, Kai Chen, Feng-Lei Jiang, Yan-Jun Hu, Dan Liu, Yi Liu, Yu-Shu Ge
Considering the vital role of cellular redox state, more and more researches focus on the design of drugs targeting thioredoxin reductase (TrxR), an important enzyme in maintaining the balance of cellular redox. Here two organic arsenicals, 2-(((4-(1,3,2-dithiarsinan-2-yl) phenyl) imino) methyl) phenol (PIM-PAO-PDT) and N-(4-(1,3,2-dithiarsinan-2-yl) phenyl)-2-hydroxybenzamide (PAM-PAO-PDT), bearing the S-As-S chemical scaffold and different linking groups have been synthesized, and both of them show the better inhibitory activity and selectivity towards HL-60 cells...
May 6, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29149820/mechanisms-of-cardioprotection-of-halogenated-agents-during-extracorporeal-circulation-in-cardiac-surgery
#4
M Ramirez Aliaga, J J Escalona Belmonte, Alicia Ramirez-Fernandez, M Rubio Navarro, J Cruz Manas
The implementation of cardioprotective strategies involving pre-, intra-, and postoperative interventions is key during cardiac surgery requiring extracorporeal circulation (ECC). The primary goal of this study was to review the physiopathology of and protection strategies against myocardial damage secondary to ECC during cardiac surgery. The administration of halogenated anesthetics for cardiac anesthesia is commonplace due to their well-known cardioprotective effects and their capacity to ensure hypnosis...
November 16, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/29149689/an-extended-sequence-specificity-for-uv-induced-dna-damage
#5
Long H Chung, Vincent Murray
The sequence specificity of UV-induced DNA damage was determined with a higher precision and accuracy than previously reported. UV light induces two major damage adducts: cyclobutane pyrimidine dimers (CPDs) and pyrimidine(6-4)pyrimidone photoproducts (6-4PPs). Employing capillary electrophoresis with laser-induced fluorescence and taking advantages of the distinct properties of the CPDs and 6-4PPs, we studied the sequence specificity of UV-induced DNA damage in a purified DNA sequence using two approaches: end-labelling and a polymerase stop/linear amplification assay...
November 2, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/29149595/sterol-oxidation-mediates-stress-responsive-vms1-translocation-to-mitochondria
#6
Jason R Nielson, Eric K Fredrickson, T Cameron Waller, Olga Zurita Rendón, Heidi L Schubert, Zhenjian Lin, Christopher P Hill, Jared Rutter
Vms1 translocates to damaged mitochondria in response to stress, whereupon its binding partner, Cdc48, contributes to mitochondrial protein homeostasis. Mitochondrial targeting of Vms1 is mediated by its conserved mitochondrial targeting domain (MTD), which, in unstressed conditions, is inhibited by intramolecular binding to the Vms1 leucine-rich sequence (LRS). Here, we report a 2.7 Å crystal structure of Vms1 that reveals that the LRS lies in a hydrophobic groove in the autoinhibited MTD. We also demonstrate that the oxidized sterol, ergosterol peroxide, is necessary and sufficient for Vms1 localization to mitochondria, through binding the MTD in an interaction that is competitive with binding to the LRS...
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29149591/mitochondrial-sterol-oxidation-marks-the-spot
#7
Lilian Lamech, Cole M Haynes
Maintenance of mitochondrial function during stress conditions is vital for cellular survival. In this issue of Molecular Cell, Nielson et al. (2017) characterize a unique domain within Vms1 that allows this protein quality control component to specifically recognize damaged or stressed compartments within the mitochondrial network.
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29149484/comparative-analysis-of-proteomes-between-diabetic-and-normal-human-sperm-insights-into-the-effects-of-diabetes-on-male-reproduction-based-on-the-regulation-of-mitochondria-related-proteins
#8
Tian An, Yue-Fen Wang, Jia-Xian Liu, Yan-Yun Pan, Yu-Fei Liu, Zhong-Chen He, Fang-Fang Mo, Jun Li, Li-Hua Kang, Yu-Jie Gu, Bo-Han Lv, Si-Huan Gao, Guang-Jian Jiang
This study sought to identify sources of the reduced fertility of men with type 2 diabetes mellitus. Significant reductions in semen volume, sperm concentration, and total sperm count were observed in diabetic individuals, while transmission electron microscopy revealed that the structure of mitochondria in the tail of sperm from diabetic patients was damaged. Proteins potentially associated with these sperm defects were identified using proteomics. Isobaric tagging for relative and absolute quantitation labeling and high-performance liquid chromatography-tandem mass spectrometry allowed us to identify 357 proteins significantly differentially expressed in diabetic versus control semen (>1...
November 17, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/29149481/neuroprotective-effects-of-melatonin-on-amphetamine-induced-dopaminergic-fiber-degeneration-in-the-hippocampus-of-postnatal-rats
#9
Tanawan Leeboonngam, Ratchadaporn Pramong, Kwankanit Sae-Ung, Piyarat Govitrapong, Pansiri Phansuwan-Pujito
Chronic amphetamine (AMPH) abuse leads to damage of the hippocampus, the brain area associated with learning and memory process. Previous results have shown that AMPH-induced dopamine neurotransmitter release, reactive oxygen species formation and degenerative protein aggregation lead to neuronal death. Melatonin, a powerful antioxidant, plays a role as a neuroprotective agent. The objective of this study was to investigate whether the protective effect of melatonin on AMPH-induced hippocampal damage in the postnatal rat acts through the dopaminergic pathway...
November 17, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/29148590/effects-of-bergenin-on-methylglyoxal-induced-damage-in-osteoblastic-mc3t3-e1-cells
#10
Kyung Hee Lee, Eun Mi Choi
Bergenin is the main chemical constituent of plants in the genus Bergenia, which are used in traditional medicines. Methylglyoxal (MG), a highly reactive dicarbonyl compound, is the major precursor for forming advanced glycation end products (AGEs). Pretreating MC3T3-E1 cells with bergenin prevented MG-induced protein adduct formation. Bergenin inhibited the MG-induced soluble receptor for AGE (sRAGE), interleukin, reactive oxygen species and mitochondrial superoxide production. Additionally bergenin increased glyoxalase I activity, glutathione, heme oxygenase-1 and nuclear factor erythroid 2-related factor 2 levels in the presence of MG...
November 17, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29147981/low-atrazine-dosages-reduce-sperm-quality-of-calomys-laucha-mice
#11
Graciela Quintana Saalfeld, Antônio Sergio Varela Junior, Tiane Castro, Fernanda Alves Pereira, Stela Mari Meneghello Gheller, Alessandra Cardoso da Silva, Carine Dahl Corcini, Carlos Eduardo da Rosa, Elton Pinto Colares
Reproductive effects caused by the exposure to environmentally relevant dosages of atrazine on wild animals are poorly understood. This study evaluated the effects of three dosages of atrazine on sperm parameters of adult Calomys laucha males. Adult mice were orally exposed to dosages of 0 (water and vehicle control), 0.1, 1, and 10 mg/kg of animal weight for a 21-day period. Following exposure, analyses were performed to determine sperm motility parameters, plasma membrane integrity and fluidity, mitochondrial functionality, acrosome integrity, DNA damage, lipid peroxidation, and production of reactive oxygen species (ROS) in the sperm samples...
November 16, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29147923/anti-aminoacyl-trna-synthetase-related-myositis-and-dermatomyositis-clues-for-differential-diagnosis-on-muscle-biopsy
#12
Bruna Cerbelli, Annalinda Pisano, Serena Colafrancesco, Maria Gemma Pignataro, Marco Biffoni, Silvia Berni, Antonia De Luca, Valeria Riccieri, Roberta Priori, Guido Valesini, Giulia d'Amati, Carla Giordano
Anti-synthetase syndrome is an autoimmune disease characterized by autoantibodies toward amino acyl-tRNA synthetases (ARS), anti-Jo 1 being the most commonly detected. Muscle damage develops in up to 90% of ARS-positive patients, characterized by a necrotizing myositis restricted to the perifascicular region. This topographic distribution of muscle damage may lead to a misdiagnosis of dermatomyositis (DM) at muscle biopsy. We compared morphological, immunohistochemical, and histoenzymatic features of muscle from ARS-positive patients (n = 11) with those of DM (n = 7) providing clues for their differential diagnosis...
November 16, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29147911/dj-1-as-a-therapeutic-target-against-cancer
#13
Ji Cao, Xiaobing Chen, Meidan Ying, Qiaojun He, Bo Yang
DJ-1 is a gene involved in various cellular processes, including transcriptional regulation, oxidative stress response, fertilization, mitochondrial regulation, inflammatory and fibrogenic niche formation, and glycation damage prevention. Although a disease-associated genetic study within the past decade has demonstrated that the mutation of DJ-1 is associated with autosomal early-onset Parkinson's disease, increasing evidence suggests that DJ-1 also plays a critical role in tumor development and progression...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29147511/cytotoxic-salen-ruthenium-iii-anticancer-complexes-exhibit-different-modes-of-cell-death-directed-by-axial-ligands
#14
Cai Li, Kwok-Wa Ip, Wai-Lun Man, Dan Song, Ming-Liang He, Shek-Man Yiu, Tai-Chu Lau, Guangyu Zhu
Two novel series of (salen)ruthenium(iii) complexes bearing guanidine and amidine axial ligands were synthesized, characterized, and evaluated for anticancer activity. In vitro cytotoxicity tests demonstrate that these complexes are cytotoxic against various cancer cell lines and the leading complexes have remarkable cancer-cell selectivity. A detailed study of the guanidine complex 7 and the amidine complex 13 reveals two distinguished modes of action. Complex 7 weakly binds to DNA and induces DNA damage, cell cycle arrest, and typical apoptosis pathways in MCF-7 cells...
October 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29146879/2-cl-mgv-1-ameliorates-apoptosis-in-the-thalamus-and-hippocampus-and-cognitive-deficits-after-cortical-infarct-in-rats
#15
Yicong Chen, Leo Veenman, Sukhdev Singh, Fubing Ouyang, Jiahui Liang, Weixian Huang, Ilan Marek, Jinsheng Zeng, Moshe Gavish
BACKGROUND AND PURPOSE: Focal cortical infarction causes neuronal apoptosis in the ipsilateral nonischemic thalamus and hippocampus, which is potentially associated with poststroke cognitive deficits. TSPO (translocator protein) is critical in regulating mitochondrial apoptosis pathways. We examined the effects of the novel TSPO ligand 2-(2-chlorophenyl)quinazolin-4-yl dimethylcarbamate (2-Cl-MGV-1) on poststroke cognitive deficits, neuronal mitochondrial apoptosis, and secondary damage in the ipsilateral thalamus and hippocampus after cortical infarction...
November 16, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29146371/comparison-of-the-protective-effect-of-black-and-white-mulberry-against-ethyl-carbamate-induced-cytotoxicity-and-oxidative-damage
#16
Yuting Li, Tao Bao, Wei Chen
Increasing evidence indicates that crude extracts derived from mulberry confer protection against oxidative stress. However, the antioxidant capacity of mulberry extract among different cultivars remains elusive. The main objective of the present study was therefore to investigate the effect of black mulberry extract (BMB) and white mulberry extract (WMB) on ethyl carbamate (EC)-induced cytotoxicity and oxidative stress. This study showed that the contents of total phenolics, total flavonoids, total procyanidins, cyanidin-3-O-glucoside, cyanidin-3-O-rutinoside and pelargonidin-3-O-glucoside of BMB were higher than that of WMB...
March 15, 2018: Food Chemistry
https://www.readbyqxmd.com/read/29146241/cardiac-progenitor-cells-activated-by-mitochondrial-delivery-of-resveratrol-enhance-the-survival-of-a-doxorubicin-induced-cardiomyopathy-mouse-model-via-the-mitochondrial-activation-of-a-damaged-myocardium
#17
Jiro Abe, Yuma Yamada, Takeda Atsuhito, Hideyoshi Harashima
It has been reported that transplanting native cells would lack efficiency without producing artificial cell-tissue, due to the exaggerated oxidative stress in doxorubicin-induced cardiomyopathy. We attempted to activate cardiac progenitor cells (CPCs) by delivering resveratrol to mitochondria using a mitochondrial drug delivery system (MITO-Porter system). We first evaluated the viability of H9c2 cells (a cardio myoblast cell line) after doxorubicin treatment, where H9c2 cells were co-cultured with or without the mitochondria activated CPCs (referred to herein as MITO cell)...
November 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29145655/paternal-exposure-to-environmental-chemical-stress-affectsmale-offspring-s-hepatic-mitochondria
#18
Roger Godschalk, Alex Remels, Camiel Hoogendoorn, Jan van Benthem, Mirjam Luijten, Nur Duale, Gunnar Brunborg, Ann-Karin Olsen, Freek G Bouwman, Armelle Munnia, Marco Peluso, Edwin Mariman, Frederik Jan van Schooten
Pre-conceptional paternal exposures may affect offspring's health, which cannot be explained by mutations in germ cells, but by persistent changes in the regulation of gene expression. Therefore, we investigated whether pre-conceptional paternal exposure to benzo[a]pyrene (B[a]P) could alter the offspring's phenotype. Male C57BL/6 mice were exposed to B[a]P by gavage for 6 weeks, 3x per week, and were crossed with unexposed BALB-c females 6 weeks after the final exposure. The offspring was kept under normal feeding conditions and was sacrificed at 3 weeks of age...
November 14, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29144508/ly6g-neutrophil-derived-mir-223-inhibits-the-nlrp3-inflammasome-in-mitochondrial-damp-induced-acute-lung-injury
#19
Zunyong Feng, Shimei Qi, Yue Zhang, Zhilin Qi, Liang Yan, Jing Zhou, Fang He, Qianqian Li, Yanyan Yang, Qun Chen, Shi Xiao, Qiang Li, Yang Chen, Yao Zhang
MicroRNA (miRNA) mediates RNA interference to regulate a variety of innate immune processes, but how miRNAs coordinate the mechanisms underlying acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in patients with pulmonary inflammatory injury is still unknown. In this study, we demonstrated that miR-223 limits the number of Ly6G+ neutrophils and inhibits the activity of the NLRP3 inflammasome to alleviate ALI induced by mitochondrial damage-associated molecular patterns (DAMPs) (MTDs). miR-223 expression is increased in the lungs of MTD-induced mice or ARDS patients following trauma/transfusion or following the physiological remission of ALI/ARDS...
November 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29144008/a-copper-ii-phenanthroline-metallopeptide-that-targets-and-disrupts-mitochondrial-function-in-breast-cancer-stem-cells
#20
Kristine Laws Laws, Ganka Bineva-Todd, Arvin Eskandari, Chunxin Lu, Nicola O'Reilly, Kogularamanan Suntharalingam
The breast cancer stem cell (CSC) and bulk breast cancer cell potency of a series of metallopeptides, 1-4 containing dichloro(1,10-phenanthroline) copper(II) and various organelle-targeting peptide sequences, is reported. The mitochondrial-targeting metallopeptide, 1 exploits the higher mitochondrial load in breast CSCs over corresponding non-CSCs, and the vulnerability of breast CSCs to mitochondrial damage, to potently and selectivity kill breast CSCs. Strikingly, 1 reduces the formation and size of mammospheres to a better extent than salinomycin, an established CSC-potent agent...
November 16, 2017: Angewandte Chemie
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