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https://www.readbyqxmd.com/read/28923379/synthesis-characterization-cellular-uptake-and-apoptosis-inducing-properties-of-two-highly-cytotoxic-cyclometalated-ruthenium-ii-%C3%AE-carboline-complexes
#1
Jincan Chen, Fa Peng, Yao Zhang, Baojun Li, Ji She, Xinming Jie, Zhilin Zou, Man Chen, Lanmei Chen
Two new cyclometalated Ru(II) complexes of the general formula [Ru(N-N)2(1-Ph-βC)](PF6), where N-N = 4,4'-dimethyl-2,2'-bipyridine (dmb, Ru1), 2,2'-bipyridine (bpy, Ru2), and 1-Ph-βC (1-phenyl-9H-pyrido[3,4-b]indole) is a β-carboline alkaloids derivatives, have been synthesized and characterized. The in vitro cytotoxicities, cellular uptake and localization, cell cycle arrest and apoptosis-inducing mechanisms of these complexes have been extensively explored by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, inductively coupled plasma mass spectrometry (ICP-MS), flow cytometry, comet assay, inverted fluorescence microscope as well as western blotting experimental techniques...
September 6, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28922794/genome-wide-variation-patterns-uncover-the-origin-and-selection-in-cultivated-ginseng-panax-ginseng-meyer
#2
Ming-Rui Li, Feng-Xue Shi, Ya-Ling Li, Peng Jiang, Lili Jiao, Bao Liu, Lin-Feng Li
Chinese ginseng (Panax ginseng Meyer) is a medicinally important herb and plays crucial roles in traditional Chinese medicine. Pharmacological analyses identified diverse bioactive components from Chinese ginseng. However, basic biological attributes including domestication and selection of the ginseng plant remain under-investigated. Here, we presented a genome-wide view of the domestication and selection of cultivated ginseng based on the whole genome data. A total of 8,660 protein-coding genes were selected for genome-wide scanning of the 30 wild and cultivated ginseng accessions...
September 1, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28922506/organoruthenium-complexes-with-c-n-ligands-are-highly-potent-cytotoxic-agents-that-act-by-a-new-mechanism-of-action
#3
Vojtech Novohradsky, Jyoti Yellol, Olga Stuchlikova, María Dolores Santana, Hana Kostrhunova, Gorakh Yellol, Jana Kasparkova, Delia Bautista, Jose Ruiz, Viktor Brabec
Our study demonstrates that four novel substitutionally inert C,N-cyclometalated Ru(II) complexes of the type [Ru(C^N)(N^N)2][PF6] containing a handle for functionalization in the C^N ligand are very potent cytotoxic agents against several different human cancer cell lines and are up to 400-fold more potent than clinically used cisplatin. In addition, the investigated ruthenium complexes are less cytotoxic in noncancerous cells, and exhibit higher selectivity for cancer cells than conventional platinum anticancer drugs...
September 18, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28921713/chebulinic-acid-isolated-from-the-fruits-of-terminalia-chebula-specifically-induces-apoptosis-in-acute-myeloid-leukemia-cells
#4
Stuti Chhabra, Tripti Mishra, Yogesh Kumar, Gatha Thacker, Sanjeev Kanojiya, Naibedya Chattopadhyay, Tadigoppula Narender, Arun Kumar Trivedi
Chebulinic acid, an ellagitannin found in the fruits of Terminalia chebula, has been extensively used in traditional Indian system of medicine. It has shown to have various biological activities including antitumor activity. The present study aims to investigate the cytotoxic potential of chebulinic acid in human myeloid leukemia cells. Interestingly, chebulinic acid caused apoptosis of acute promyelocytic leukemia HL-60 and NB4 cells but not K562 cells. In vitro antitumor effects of chebulinic acid were investigated by using various acute myeloid leukemia cell lines...
September 18, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28910489/nucleoside-nucleotide-reverse-transcriptase-inhibitors-attenuate-angiogenesis-and-lymphangiogenesis-by-impairing-receptor-tyrosine-kinases-signalling-in-endothelial-cells
#5
Lin Song, Sha Ding, Zhen Ge, Xiaolong Zhu, Cong Qiu, Yuewen Wang, Enyin Lai, Weijun Yang, Yi Sun, Samson A Chow, Luyang Yu
BACKGROUND AND PURPOSE: Cardiovascular disease associated with antiretroviral therapy (ART) has become a major clinical challenge for HIV-positive patients. However, the role of ART in blood vessel growth is largely unknown. Here, we examined an integral component of ART, nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), and investigated their effects on key microvascular functions, including angiogenesis and lymphangiogenesis. EXPERIMENTAL APPROACH: The angiogenesis/lymphangiogenesis capability of endothelial cells (ECs) was evaluated using migration, proliferation and tube formation assays in vitro, and mouse ear and Matrigel plug assays in vivo...
September 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28905672/the-influence-of-ketogenic-therapy-on-the-5-r-s-of-radiobiology
#6
Rainer J Klement
PURPOSE: Radiotherapy (RT) is a mainstay in the treatment of solid tumors and works by inducing free radical stress in tumor cells, leading to loss of reproductive integrity. The optimal treatment strategy has to consider damage to both tumor and normal cells and is determined by five factors known as the 5 R's of radiobiology: Reoxygenation, DNA Repair, Radiosensitivity, Redistribution in the cell cycle and Repopulation. The aim of this review is (i) to present evidence that these 5 R's are strongly influenced by cellular and whole body metabolism that in turn can be modified through ketogenic therapy in form of ketogenic diets and short term fasting, and (ii) to stimulate new research into this field including some research questions deserving further study...
September 14, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28904196/vaccinia-virus-encodes-a-novel-inhibitor-of-apoptosis-that-associates-with-the-apoptosome
#7
Melissa R Ryerson, Monique M Richards, Marc Kvansakul, Christine J Hawkins, Joanna L Shisler
Apoptosis is an important anti-viral host defense mechanism. Here we report the identification of a novel apoptosis inhibitor encoded by the vaccinia virus (VACV) M1L gene. M1L is absent in the attenuated MVA strain of VACV, a strain that stimulates apoptosis in several types of immune cells. M1 expression increased the viability of MVA-infected THP-1 and Jurkat cells and reduced several biochemical hallmarks of apoptosis such as PARP-1 and procaspase-3 cleavage. Furthermore, ectopic M1L expression decreased staurosporine-induced (intrinsic) apoptosis in HeLa cells...
September 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28903409/acetyl-lupeolic-acid-inhibits-akt-signaling-and-induces-apoptosis-in-chemoresistant-prostate-cancer-cells-in-vitro-and-in-vivo
#8
Claudia Schmidt, Cornelia Loos, Lu Jin, Michael Schmiech, Christoph Q Schmidt, Menna El Gaafary, Tatiana Syrovets, Thomas Simmet
The triterpenoid acetyl-lupeolic acid (ac-LA) isolated from the oleogum resin of Boswellia carterii reduced the viability of a panel of cancer cell lines more efficiently than lupeol. There was no detectable intracellular conversion of ac-LA to lupeol and vice versa. In contrast to docetaxel, ac-LA did not induce selection of treatment-resistant cancer cells. By various parameters including DNA fragmentation, ac-LA was shown to induce apoptosis in androgen-independent PC-3 cells, whereas in MDA-MB-231 breast cancer cells, ac-LA led to cell accumulation in the G2/M phase of the cell cycle, but not to apoptosis...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28893537/cytoplasmic-transfer-of-heritable-elements-other-than-mtdna-from-samp1-mice-into-mouse-tumor-cells-suppresses-their-ability-to-form-tumors-in-c57bl6-mice
#9
Akinori Shimizu, Haruna Tani, Gaku Takibuchi, Kaori Ishikawa, Ryota Sakurazawa, Takafumi Inoue, Tetsuo Hashimoto, Kazuto Nakada, Keizo Takenaga, Jun-Ichi Hayashi
In a previous study, we generated transmitochondrial P29mtSAMP1 cybrids, which had nuclear DNA from the C57BL6 (referred to as B6) mouse strain-derived P29 tumor cells and mitochondrial DNA (mtDNA) exogenously-transferred from the allogeneic strain SAMP1. Because P29mtSAMP1 cybrids did not form tumors in syngeneic B6 mice, we proposed that allogeneic SAMP1 mtDNA suppressed tumor formation of P29mtSAMP1 cybrids. To test this hypothesis, current study generated P29mt(sp)B6 cybrids carrying all genomes (nuclear DNA and mtDNA) from syngeneic B6 mice by eliminating SAMP1 mtDNA from P29mtSAMP1 cybrids and reintroducing B6 mtDNA...
September 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28890317/mitoneod-a-mitochondria-targeted-superoxide-probe
#10
Maria M Shchepinova, Andrew G Cairns, Tracy A Prime, Angela Logan, Andrew M James, Andrew R Hall, Sara Vidoni, Sabine Arndt, Stuart T Caldwell, Hiran A Prag, Victoria R Pell, Thomas Krieg, John F Mulvey, Pooja Yadav, James N Cobley, Thomas P Bright, Hans M Senn, Robert F Anderson, Michael P Murphy, Richard C Hartley
Mitochondrial superoxide (O2(⋅-)) underlies much oxidative damage and redox signaling. Fluorescent probes can detect O2(⋅-), but are of limited applicability in vivo, while in cells their usefulness is constrained by side reactions and DNA intercalation. To overcome these limitations, we developed a dual-purpose mitochondrial O2(⋅-) probe, MitoNeoD, which can assess O2(⋅-) changes in vivo by mass spectrometry and in vitro by fluorescence. MitoNeoD comprises a O2(⋅-)-sensitive reduced phenanthridinium moiety modified to prevent DNA intercalation, as well as a carbon-deuterium bond to enhance its selectivity for O2(⋅-) over non-specific oxidation, and a triphenylphosphonium lipophilic cation moiety leading to the rapid accumulation within mitochondria...
August 24, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28882896/transcriptional-fidelities-of-human-mitochondrial-polrmt-yeast-mitochondrial-rpo41-and-phage-t7-single-subunit-rna-polymerases
#11
Shemaila Sultana, Mihai Solotchi, Aparna Ramachandran, Smita S Patel
Single-subunit RNA polymerases (RNAPs) are present in phage T7 and in mitochondria of all eukaryotes. This RNAP class plays important roles in biotechnology and cellular energy production, but we know little about its fidelity and error rates. Herein, we report the error rates of three single-subunit RNAPs measured from the catalytic efficiencies of correct and all possible incorrect nucleotides. The average error rate of T7 RNAP (2×10-6), yeast mitochondrial Rpo41 (6×10-6), and human mitochondrial POLRMT (2×10-5) indicates high accuracy/fidelity of RNA synthesis resembling those of replicative DNA polymerases...
September 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28878314/limited-locomotive-ability-relaxed-selective-constraints-on-molluscs-mitochondrial-genomes
#12
Shao'e Sun, Qi Li, Lingfeng Kong, Hong Yu
Mollusca are the second largest phylum in the animal kingdom with different types of locomotion. Some molluscs are poor-migrating, while others are free-moving or fast-swimming. Most of the energy required for locomotion is provided by mitochondria via oxidative phosphorylation. Here, we conduct a comparative genomic analysis of 256 molluscs complete mitochondrial genomes and evaluate the role of energetic functional constraints on the protein-coding genes, providing a new insight into mitochondrial DNA (mtDNA) evolution...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28870729/tigecylcine-induced-inhibition-of-mitochondrial-mtdna-translation-may-cause-a-lethal-mitochondrial-dysfunction-in-human
#13
S J Vandecasteele, S Seneca, J Smet, M Reynders, J De Ceulaer, A V Vanlander, R Van Coster
OBJECTIVES: A 65-year old patient developed an unexplained and ultimately lethal metabolic acidosis under prolonged treatment with tigecycline. Tigecycline is known to have a selective inhibitory effect on eukaryotic mitochondrial translation. The underlying molecular mechanisms of the metabolic acidosis in this patient were explored. METHODS: OXPHOS analysis, blue native PAGE followed by in-gel activity staining in mitochondria, molecular analysis of mtDNA for genomic rearrangements and sequencing of the rRNA genes was performed on the proband's skeletal muscle...
September 1, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28866057/mitochondrial-disruption-in-peroxisome-deficient-cells-is-hepatocyte-selective-but-is-not-mediated-by-common-hepatic-peroxisomal-metabolites
#14
Abhijit Babaji Shinde, Ritesh Kumar Baboota, Simone Denis, Ursula Loizides-Mangold, Annelies Peeters, Marc Espeel, Ana Rita Malheiro, Howard Riezman, Stefan Vinckier, Frédéric M Vaz, Pedro Brites, Sacha Ferdinandusse, Paul P Van Veldhoven, Myriam Baes
The structural disruption of the mitochondrial inner membrane in hepatocytes lacking functional peroxisomes along with selective impairment of respiratory complexes and depletion of mitochondrial DNA was previously reported. In search for the molecular origin of these mitochondrial alterations, we here show that these are tissue selective as they do neither occur in peroxisome deficient brain nor in peroxisome deficient striated muscle. Given the hepatocyte selectivity, we investigated the potential involvement of metabolites that are primarily handled by hepatic peroxisomes...
August 30, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28854730/reply-purifying-selection-on-mitochondrial-dna-a-strategy-for-the-oocyte-to-preserve-competence
#15
M Cristina Magli, Sara De Fanti, Saverio Vicario, Martin Lang, Domenico Simone, Donata Luiselli, Giovanni Romeo, Luca Gianaroli
No abstract text is available yet for this article.
September 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28854729/purifying-selection-on-mitochondrial-dna-in-maturing-oocytes-implication-for-mitochondrial-replacement-therapy
#16
Jan Tesarik
No abstract text is available yet for this article.
September 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28854642/papio-baboon-species-indicative-alu-elements
#17
Jerilyn A Walker, Vallmer E Jordan, Cody J Steely, Thomas O Beckstrom, Cullen L McDaniel, Corey P St Romain, Emily C Bennett, Arianna Robichaux, Brooke N Clement, Miriam K Konkel, Mark A Batzer
The genus of Papio (baboon) has six recognized species separated into Northern and Southern clades, each comprised of three species distributed across the African continent. Geographic origin and phenotypic variants such as coat color and body size have commonly been used to identify different species. The existence of multiple hybrid zones, both ancient and current, have complicated efforts to characterize the phylogeny of Papio baboons. More recently, mitochondrial DNA (mtDNA) and Y-chromosome genetic markers have been utilized for species identification with particular focus on the hybrid zones...
June 1, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28844488/the-genetic-legacy-of-zoroastrianism-in-iran-and-india-insights-into-population-structure-gene-flow-and-selection
#18
Saioa López, Mark G Thomas, Lucy van Dorp, Naser Ansari-Pour, Sarah Stewart, Abigail L Jones, Erik Jelinek, Lounès Chikhi, Tudor Parfitt, Neil Bradman, Michael E Weale, Garrett Hellenthal
Zoroastrianism is one of the oldest extant religions in the world, originating in Persia (present-day Iran) during the second millennium BCE. Historical records indicate that migrants from Persia brought Zoroastrianism to India, but there is debate over the timing of these migrations. Here we present genome-wide autosomal, Y chromosome, and mitochondrial DNA data from Iranian and Indian Zoroastrians and neighboring modern-day Indian and Iranian populations and conduct a comprehensive genome-wide genetic analysis in these groups...
September 7, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28837577/reduced-genetic-diversity-and-alteration-of-gene-flow-in-a-fiddler-crab-due-to-mangrove-degradation
#19
Alex Nehemia, Marc Kochzius
The fiddler crab Austruca occidentalis is a dominant species in mangrove forests along the East African coast. It enhances soil aeration and, through its engineering activities, makes otherwise-inaccessible food available for other marine organisms. Despite its importance, the habitat of A. occidentalis is threatened by human activities. Clearing the mangroves for salt farming and selective logging of mangroves trees continue to jeopardise mangrove ecosystems in the Western Indian Ocean. This study aims to use partial mitochondrial COI gene sequences and nuclear microsatellites to determine whether salt farming activities in mangroves have a negative impact on the genetic diversity and gene flow of A...
2017: PloS One
https://www.readbyqxmd.com/read/28832998/dynamic-monitoring-of-p53-translocation-to-mitochondria-for-the-analysis-of-specific-inhibitors-using-luciferase-fragment-complementation
#20
Natsumi Noda, Raheela Awais, Robert Sutton, Muhammad Awais, Takeaki Ozawa
Intracellular protein translocation plays a pivotal role in regulating complex biological processes, including cell death. The tumor suppressor p53 is a transcription factor activated by DNA damage and oxidative stress that also translocates from the cytosol into the mitochondrial matrix to facilitate necrotic cell death. However, specific inhibitors of p53 mitochondrial translocation are largely unknown. To explore the inhibitors of p53, we developed a bioluminescent probe to monitor p53 translocation from cytosol to mitochondria using luciferase fragment complementation assays...
August 19, 2017: Biotechnology and Bioengineering
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