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https://www.readbyqxmd.com/read/29150633/ketamine-s-antidepressant-effect-is-mediated-by-energy-metabolism-and-antioxidant-defense-system
#1
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
#2
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/29149595/sterol-oxidation-mediates-stress-responsive-vms1-translocation-to-mitochondria
#3
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/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
#4
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/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
#5
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
#6
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/29144008/a-copper-ii-phenanthroline-metallopeptide-that-targets-and-disrupts-mitochondrial-function-in-breast-cancer-stem-cells
#7
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
https://www.readbyqxmd.com/read/29143358/melatonin-improves-survival-and-respiratory-activity-of-yeast-cells-challenged-by-alpha-synuclein-and-menadione
#8
Mariana A Zampol, Mario H Barros
One of the hallmarks of Parkinson disease is α-synuclein aggregate deposition that leads to ER stress, Golgi fragmentation, and impaired energy metabolism with consequent redox imbalance. In the last decade, many studies have used Saccharomyces cerevisiae as a model in order to explore the intracellular consequences of α-synuclein overexpression. In this study we propose to evaluate the respiratory outcome of yeast cells expressing α-synuclein. Cell viability, or growth on selective media for respiratory activity was mainly affected in the α-synuclein expressing cells if they were also treated with menadione, which stimulates ROS production...
November 16, 2017: Yeast
https://www.readbyqxmd.com/read/29143351/apoptotic-and-antiproliferative-properties-of-3%C3%AE-hydroxy-%C3%AE-5-steroidal-congeners-from-a-partially-purified-column-fraction-of-dendronephthya-gigantea-against-hl-60-and-mcf-7-cancer-cells
#9
I P Shanura Fernando, K K Asanka Sanjeewa, Hyun-Soo Kim, Lei Wang, Won Woo Lee, You-Jin Jeon
Organisms belonging to the genus Dendronephthya are among a group of marine invertebrates that produce a variety of terpenoids with biofunctional properties. Many of these terpenoids have been proven effective as anticancer drugs. Here, we report the antiproliferative effect of 3β-hydroxy-Δ5-steroidal congeners against the proliferation of HL-60 human leukemia cells and MCF-7 human breast cancer cells. The sterol-rich fraction (DGEHF2-1) inhibited the growth of HL-60 and MCF-7 cells with IC50 values of 13...
November 16, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29140794/targeted-elimination-of-senescent-ras-transformed-cells-by-suppression-of-mek-erk-pathway
#10
Elena Y Kochetkova, Galina I Blinova, Olga A Bystrova, Marina G Martynova, Valery A Pospelov, Tatiana V Pospelova
The Ras-Raf-MEK-ERK pathway plays a central role in tumorigenesis and is a target for anticancer therapy. The successful strategy based on the activation of cell death in Ras-expressing cells is associated with the suppression of kinases involved in Ras pathway. However, activation of cytoprotective autophagy overcomes antiproliferative effect of the inhibitors and develops drug resistance. We studied whether cellular senescence induced by HDAC inhibitor sodium butyrate in E1a+cHa-Ras-transformed rat embryo fibroblasts (ERas) and A549 human Ki-Ras mutated lung adenocarcinoma cells would enhance the tumor suppressor effect of MEK/ERK inhibition...
November 14, 2017: Aging
https://www.readbyqxmd.com/read/29140245/bacterial-fumarase-and-l-malic-acid-are-evolutionary-ancient-components-of-the-dna-damage-response
#11
Esti Singer, Yardena Bh Silas, Sigal Ben-Yehuda, Ophry Pines
Fumarase is distributed between two compartments of the eukaryotic cell. The enzyme catalyses the reversible conversion of fumaric to L-malic acid in mitochondria as part of the tricarboxylic acid (TCA) cycle, and in the cytosol/nucleus as part of the DNA damage response (DDR). Here we show that fumarase of the model prokaryote Bacillus subtilis (Fum-bc) is induced upon DNA damage, co-localized with the bacterial DNA and is required for the DDR. Fum-bc can substitute for both eukaryotic functions in yeast. Furthermore, we found that the fumarase dependent intracellular signaling of the B...
November 15, 2017: ELife
https://www.readbyqxmd.com/read/29138454/differences-in-mitochondrial-function-and-morphology-during-cooling-and-rewarming-between-hibernator-and-non-hibernator-derived-kidney-epithelial-cells
#12
Koen D W Hendriks, Eleonora Lupi, Maarten C Hardenberg, Femke Hoogstra-Berends, Leo E Deelman, Robert H Henning
Hibernators show superior resistance to ischemia and hypothermia, also outside the hibernation season. Therefore, hibernation is a promising strategy to decrease cellular damage in a variety of fields, such as organ transplantation. Here, we explored the role of mitochondria herein, by comparing epithelial cell lines from a hibernator (hamster kidney cells, HaK) and a non-hibernator (human embryonic kidney cells, HEK293) during cold preservation at 4 °C and rewarming. Cell survival (Neutral Red), ATP and MDA levels, mitochondrial membrane potential (MMP), mitochondrial morphology (using fluorescent probes) and metabolism (seahorse XF) were assessed...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29136781/andrographolide-sulfonate-improves-alzheimer-associated-phenotypes-and-mitochondrial-dysfunction-in-app-ps1-transgenic-mice
#13
Ji Geng, Wen Liu, Yuyun Xiong, Hongqun Ding, Chunhong Jiang, Xiaoling Yang, Xiang Li, Ahmed Elgehama, Yang Sun, Qiang Xu, Wenjie Guo, Jing Gao
Alzheimer's disease is a neurodegenerative disorder with Amyloid-β plaques onset, synaptic damage, and cognitive decline. Aβ deposits cause pathological events including oxidative stress, mitochondrial dysfunction, and neuron death. In this study, APPswe/PSENΔ9 double transgenic mice model was used to imitate Alzheimer's disease and the effect and possible mechanism of Andrographolide sulfonate were examined. Andrographolide sulfonate was given to the mice for 7 months before the onset of Aβ plaque. Spatial memory test showed that Andrographolide sulfonate treatment prevented cognitive decline...
November 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29135887/ischemia-reperfusion-injury-in-aged-livers-the-energy-metabolism-inflammatory-response-and-autophagy
#14
Chunyi Kan, Luisa Ungelenk, Amelie Lupp, Olaf Dirsch, Uta Dahmen
Due to the lack of adequate organs, the number of patients with end-stage liver diseases, acute liver failure or hepatic malignancies waiting for liver transplantation is constantly increasing. Accepting aged liver grafts is one of the strategies expanding the donor pool to ease the discrepancy between the growing demand and the limited supply of donor organs. However, recipients of organs from old donors may show an increased post-transplantation morbidity and mortality due to enhanced ischemia reperfusion injury...
November 11, 2017: Transplantation
https://www.readbyqxmd.com/read/29133922/essential-role-of-mitochondrial-stat3-in-p38-mapk-mediated-apoptosis-under-oxidative-stress
#15
Xinlai Cheng, Christiane Peuckert, Stefan Wölfl
Stat3 is an oncogene, frequently associated with malignant transformation. A body of evidence implicates that phospho-Stat3(Y705) contributes to its nucleic translocation, while phospho-Stat3(S727) leads to the accumulation in mitochondria. Both are of importance for tumor cell proliferation. In comparison to well-characterized signaling pathways interplaying with Stat3(Y705), little is known about Stat3(S727). In this work, we studied the influence of Stat3 deficiency on the viability of cells exposed to H2O2 or hypoxia using siRNA and CRISPR/Cas9 genome-editing...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29133631/mitochondrial-genetics-and-therapeutic-overview-of-leber-s-hereditary-optic-neuropathy
#16
REVIEW
Agaath Hedina Manickam, Minu Jenifer Michael, Sivasamy Ramasamy
Leber's hereditary optic neuropathy (LHON) is a common inherited mitochondrial disorder that is characterized by the degeneration of the optic nerves, leading to vision loss. The major mutations in the mitochondrial genes ND1, ND4, and ND6 of LHON subjects are found to increase the oxidative stress experienced by the optic nerve cell, thereby leading to nerve cell damage. Accurate treatments are not available and drugs that are commercially available like Idebenone, EPI-743, and Bendavia with their antioxidant role help in reducing the oxidative stress experienced by the cell thereby preventing the progression of the disease...
November 2017: Indian Journal of Ophthalmology
https://www.readbyqxmd.com/read/29132816/deferiprone-inhibits-iron-overload-induced-tissue-factor-bearing-endothelial-microparticle-generation-by-inhibition-oxidative-stress-induced-mitochondrial-injury-and-apoptosis
#17
Shing Chan, Qizhou Lian, Mei-Pian Chen, Dan Jiang, Jolie T K Ho, Yiu-Fai Cheung, Godfrey C F Chan
Iron overload-induced cardiovascular toxicity is one of the most common causes of morbidity and mortality in beta-thalassemia major patients. We have previously shown that iron overload-induced systemic arterial changes characterized by endothelial dysfunction are associated with increased endothelial microparticle (EMP) release. In this study, we further demonstrate how EMP release is associated with iron-induced mitochondrial injury and apoptosis of endothelial cells. Iron increased the production of reactive oxygen species (ROS) and calcium influx into mitochondria [Ca(2+)]m...
November 10, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29132140/mitochondria-targeted-peptide-attenuates-mitochondrial-dysfunction-controls-inflammation-and-protects-against-spinal-cord-injury-induced-lung-injury
#18
Liu-Long Zhu, Mao-Qiang Li, Fan He, Shao-Bo Zhou, Wu Jiang
BACKGROUND/AIMS: Spinal cord injury (SCI) is a common and devastating disease, which results in systemic inflammatory response syndrome and secondary lung injury. Mitochondrial dysfunction and inflammation are closely related to lung injury in diverse disease models. No studies have demonstrated the effects of mitochondrial targeted peptide SS-31 in a mouse model of SCI-induced lung injury. METHODS: Immediately after injury, mice in the treatment groups received a daily, single-dose intraperitoneal injection of SS-31 and for the next 2 days...
November 13, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29131056/chloride-intracellular-channel-4-overexpression-in-the-proximal-tubules-of-kidneys-from-the-spontaneously-hypertensive-rat-insight-from-proteomic-analysis
#19
Diane Hatziioanou, Georgios Barkas, Elena Critselis, Jerome Zoidakis, Hariklia Gakiopoulou, Maria-Eleni Androutsou, Garyfalia Drossopoulou, Aristidis Charonis, Demetrios V Vlahakos
BACKGROUND: Hypertensive nephropathy, a leading cause of declining kidney function, is a multifactorial process not well understood. In order to elucidate biological processes and identify novel macromolecular components crucially involved in the process of kidney damage, the application of system biology approaches, like proteomics, is required. METHODS: Proteomic studies were performed using the renal parenchyma of spontaneously hypertensive rats (SHR) and their normotensive Wistar Kyoto controls...
November 7, 2017: Nephron
https://www.readbyqxmd.com/read/29130578/sirt3-deregulation-is-linked-to-mitochondrial-dysfunction-in-alzheimer-s-disease
#20
Junghee Lee, Yunha Kim, Tian Liu, Yu Jin Hwang, Seung Jae Hyeon, Hyeonjoo Im, Kyungeun Lee, Victor E Alvarez, Ann C McKee, Soo-Jong Um, Manwook Hur, Inhee Mook-Jung, Neil W Kowall, Hoon Ryu
Alzheimer's disease (AD) is the leading cause of dementia in the elderly. Despite decades of study, effective treatments for AD are lacking. Mitochondrial dysfunction has been closely linked to the pathogenesis of AD, but the relationship between mitochondrial pathology and neuronal damage is poorly understood. Sirtuins (SIRT, silent mating type information regulation 2 homolog in yeast) are NAD-dependent histone deacetylases involved in aging and longevity. The objective of this study was to investigate the relationship between SIRT3 and mitochondrial function and neuronal activity in AD...
November 11, 2017: Aging Cell
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