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DNA damage

Chun-Hao Li, Sa-Hoe Lim, Hyang-Hwa Ryu, Kyung-Sub Moon, Tae-Young Jung, Shin Jung
Stereotactic radiosurgery has been recognized as an effective treatment approach for metastatic brain tumors. By increasing the sensitivity of the tumor to radiation and decreasing the marginal dose, it is possible to improve therapeutic efficacy and decrease side-effects. In radiation-induced cells, c-Jun N-terminal kinase (JNK) signaling mediates the phosphorylation of H2AX, which indicates DNA damage sensitivity and modulates the effect of radiation. Lewis lung cancer (LLC) and breast cancer (4T1) cells were irradiated with a Gamma Knife in cell culture tubes...
October 25, 2016: Oncology Reports
Ziyao Wang, Tinghe Yu, Ping Huang
The Forkhead box O (FOXO) protein family is predominantly involved in apoptosis, oxidative stress, DNA damage/repair, tumor angiogenesis, glycometabolism, regulating life span and other important biological processes. Its activity is affected by a variety of posttranslational modifications (PTMs), including phosphorylation, acetylation, ubiquitination, methylation and glycosylation. When cells are subjected to different environments, the corresponding PTMs act on the FOXO protein family, to change transcriptional activity or subcellular localization, and the expression of downstream target genes, will ultimately affect the biological behavior of the cells...
October 20, 2016: Molecular Medicine Reports
Gizem Ölmezer, Maryna Levikova, Dominique Klein, Benoît Falquet, Gabriele Alessandro Fontana, Petr Cejka, Ulrich Rass
Cells have evolved mechanisms to protect, restart and repair perturbed replication forks, allowing full genome duplication, even under replication stress. Interrogating the interplay between nuclease-helicase Dna2 and Holliday junction (HJ) resolvase Yen1, we find the Dna2 helicase activity acts parallel to homologous recombination (HR) in promoting DNA replication and chromosome detachment at mitosis after replication fork stalling. Yen1, but not the HJ resolvases Slx1-Slx4 and Mus81-Mms4, safeguards chromosome segregation by removing replication intermediates that escape Dna2...
October 25, 2016: Nature Communications
Egor Bobrov, Natalia Skobeleva, Diana Restifo, Natalya Beglyarova, Kathy Q Cai, Elizabeth Handorf, Kerry Campbell, David A Proia, Vladimir Khazak, Erica A Golemis, Igor Astsaturov
The lack of effective treatment modalities is a major problem in pancreatic cancer (PCa), a devastating malignancy that is nearly universally driven by the "undruggable" KRAS and TP53 cancer genes. Poor tumor tissue penetration is the major source of resistance in pancreatic cancer where chemotherapy is the mainstay of treatment. In this study we exploited the selective tumor-targeting properties of the heat shock 90 protein inhibitors as the vehicle for drug delivery to pancreatic tumor tissues. STA-12-8666 is a novel esterase-cleavable conjugate of an HSP90i and a topoisomerase I inhibitor, SN-38...
October 13, 2016: Oncotarget
Ewa Kosior-Jarecka, Dominika Wróbel-Dudzińska, Urszula Łukasik, Tin Aung, Chiea Chuen Khor, Janusz Kocki, Tomasz Żarnowski
PURPOSE: The purpose of this study was to determine whether four single nucleotide polymorphisms (SNPs) of endothelin and endothelin receptor type A genes can constitute a risk factor for normal tension glaucoma (NTG) and high tension glaucoma (HTG). METHODS: The study included 160 patients with NTG, 124 patients with HTG, and 165 healthy controls. To analyze the frequency of polymorphic variants of the endothelin EDN gene (K198N) and the endothelin receptor type A gene EDN RA (C1222T, C70G, G231A), DNA was isolated from peripheral blood, and SNP genotyping was performed using the real-time PCR (RT-PCR) method...
2016: Molecular Vision
Satomi Miwa, Rafal Czapiewski, Tengfei Wan, Amy Bell, Kirsten N Hill, Thomas von Zglinicki, Gabriele Saretzki
Telomerase in its canonical function maintains telomeres in dividing cells. In addition, the telomerase protein TERT has non-telomeric functions such as shuttling to mitochondria resulting in a decreased oxidative stress, DNA damage and apoptosis. TERT protein persists in adult neurons and can co-localise to mitochondria under various stress conditions. We show here that TERT expression decreased in mouse brain during aging while release of reactive oxygen species (ROS) from the mitochondrial electron transport chain increased...
October 22, 2016: Aging
Cheng-Cao Sun, Shu-Jun Li, Zhan-Peng Yuan, De-Jia Li
Determinants of growth and metastasis in cancer remain of great interest to define. MicroRNAs (miRNAs) have frequently emerged as tumor metastatic regulator by acting on multiple signaling pathways. Here we report the definition of miR-346 as a novel oncogenic microRNA that facilitates non-small cell lung cancer (NSCLC) cell growth and metastasis. XPC, an important DNA damage recognition factor in nucleotide excision repair was defined as a target for down-regulation by miR-346, functioning through direct interaction with the 3'-UTR of XPC mRNA...
October 18, 2016: Aging
Ricardo I Peraza-Vega, América N Castañeda-Sortibrán, Mahara Valverde, Emilio Rojas, Rosario Rodríguez-Arnaiz
The aim of this study was to evaluate the genotoxicity of the herbicide diuron in the wing-spot test and a novel wing imaginal disk comet assay in Drosophila melanogaster The wing-spot test was performed with standard (ST) and high-bioactivation (HB) crosses after providing chronic 48 h treatment to third instar larvae. A positive dose-response effect was observed in both crosses, but statistically reduced spot frequencies were registered for the HB cross compared with the ST. This latter finding suggests that metabolism differences play an important role in the genotoxic effect of diuron...
October 24, 2016: Toxicology and Industrial Health
Doc Mariano, D de Souza, D F Meinerz, J Allebrandt, A F de Bem, W Hassan, Oed Rodrigues, Jbt da Rocha
Acquired immunodeficiency syndrome (AIDS) is a worldwide disease characterized by impairments of immune function. AIDS can be associated with oxidative stress (OS) that can be linked to selenium (Se) deficiency. Se is fundamental for the synthesis of selenoproteins, such as glutathione peroxidase and thioredoxin reductase. These enzymes catalyze the decomposition of reactive oxygen species and contribute to maintain equilibrium in cell redox status. Literature data indicate that organoselenium compounds, such as ebselen and diphenyl diselenide, have antioxidant properties in vitro and in vivo models associated with OS...
October 24, 2016: Human & Experimental Toxicology
Xing Liu, Xiaolian Cai, Bo Hu, Zhichao Mei, Dawei Zhang, Gang Ouyang, Jing Wang, Wei Zhang, Wuhan Xiao
FOXO3a, a member of the forkhead homeobox type O (FOXO) family of transcriptional factors, regulates cell survival in response to DNA damage, caloric restriction, and oxidative stress. The von Hippel-Lindau (VHL) tumor suppressor gene encodes a component of the E3 ubiquitin ligase complex that mediates hypoxia-inducible factor-α (HIF-α) degradation under aerobic conditions, thus acting as one of the key regulators of hypoxia signaling. However, whether FOXO3a impacts cellular hypoxia stress remains unknown...
October 24, 2016: Journal of Biological Chemistry
Castrese Morrone, Riccardo Miggiano, Mario Serpe, Alberto Massarotti, Anna Valenti, Giovanni Del Monaco, Mosè Rossi, Franca Rossi, Menico Rizzi, Giuseppe Perugino, Maria Ciaramella
BACKGROUND: Alkylated DNA-protein alkyltransferases (AGTs) are conserved proteins that repair alkylation damage in DNA by using a single-step mechanism leading to irreversible alkylation of the catalytic cysteine in the active site. Trans-alkylation induces inactivation and destabilization of the protein, both in vitro and in vivo, likely triggering conformational changes. A complete picture of structural rearrangements occurring during the reaction cycle is missing, despite considerable interest raised by the peculiarity of AGT reaction, and the contribution of a functional AGT in limiting the efficacy of chemotherapy with alkylating drugs...
October 21, 2016: Biochimica et Biophysica Acta
Hanen Ferjani, Hossam Draz, Salwa Abid, Abedellatif Achour, Hassen Bacha, Imen Boussema-Ayed
Tacrolimus (TAC) and mycophenolate mofetil (MMF) are common immunosuppressive drugs used to avoid immunological rejection of transplanted organs. The risk of developing cancer is the most critical complication in organ transplant recipients undergoing immunosuppressive therapy. This study aims to explore the cytotoxic and genotoxic effects of TAC and MMF alone or combined orally administrated on spleen and bone marrow of Wistar rats. Our results showed that TAC (2.4; 24 and 60mg/kg) and MMF (5; 50 and 125mg/kg) induced a genotoxic effect on rat bone marrow...
November 1, 2016: Mutation Research
Rangel Moreira Silva, Luciane Dias Pereira, Jefferson Hollanda Véras, Camila Regina do Vale, Lee Chen-Chen, Suzana da Costa Santos
Ellagitannins are well-known antioxidants in medicinal plants, foods, and edible fruits, particularly in Myrciaria cauliflora (jabuticaba). Thus, this study aimed to evaluate the protective effects of jabuticaba seed extract (JSE) and pedunculagin using in vivo micronucleus test and comet assay in mouse bone marrow cells, in combination with cyclophosphamide (CP), a bioreductive alkylating agent. The ellagitannin composition of JSE was determined by HPLC/PDA, with castalagin, vescalagin, and pedunculagin as the main compounds (124...
November 1, 2016: Mutation Research
Hala Attia, Nouf Al-Rasheed, Raeesa Mohamad, Nawal Al-Rasheed, Maha Al-Amin
BACKGROUND: Hepatic fibrosis and its end point; cirrhosis, are the major cause of liver failure and death in patients with chronic liver disease. Therefore, the need for an effective treatment is evident. This study was designed to assess the potential effects of aqueous extract of date fruits, either flesh (DFE) or pits (DPE), on oxidative DNA damage and liver inflammation induced by carbon tetrachloride (CCl4) and whether they are related to inhibition of nuclear factor-κB pathway...
October 24, 2016: BMC Complementary and Alternative Medicine
Tahira Younis, Muhammad Rashid Khan, Moniba Sajid
BACKGROUND: Leaves and root bark of Fraxinus xanthoxyloides Wall. (Oleaceae) are used locally for the treatment of jaundice, malaria and pneumonia. Decoction of stem, twigs and bark is used in pain, internal injuries, rheumatism and in bone fracture. In this investigation we have evaluated the methanol extract of leaves for its hepatoprotective potential against CCl4 induced hepatic injuries in rat. METHODS: Powder of F. xanthoxyloides leaves was extracted with methanol (FXM) and subjected for the determination of polyphenolics through HPLC-DAD analysis...
October 24, 2016: BMC Complementary and Alternative Medicine
Chrysoula Konstantinidou, Stavros Taraviras, Vassilis Pachnis
BACKGROUND: In vertebrate organisms, the neural crest (NC) gives rise to multipotential and highly migratory progenitors which are distributed throughout the embryo and generate, among other structures, the peripheral nervous system, including the intrinsic neuroglial networks of the gut, i.e. the enteric nervous system (ENS). The majority of enteric neurons and glia originate from vagal NC-derived progenitors which invade the foregut mesenchyme and migrate rostro-caudally to colonise the entire length of the gut...
October 24, 2016: BMC Biology
Félix Javier Jiménez-Jiménez, Hortensia Alonso-Navarro, María Trinidad Herrero, Elena García-Martín, José A G Agúndez
BACKGROUND: The pathogenesis of Parkinson's disease (PD) is not fully understood. Together with some important physiological functions in the Central Nervous System (CNS), nitric oxide (NO) can have both, neuroprotective or neurotoxic actions, depending on its redox state. An important body of evidence suggests the involvement of NO in many of the processes leading to neurodegeneration in several neurological disorders including PD. OBJECTIVE: The main aim of this review is to update the data regarding the possible involvement of NO in the pathogenesis of PD...
2016: Current Medicinal Chemistry
Akihisa Takahashi, Eiichiro Mori, Yosuke Nakagawa, Atsuhisa Kajihara, Tadaaki Kirita, L Pittman Douglas, Masatoshi Hasegawa, Takeo Ohnishi
PURPOSE: Heat shock induces DNA double-strand breaks (DSBs), but the precise mechanism of repairing heat-induced damage is unclear. Here, we investigated the DNA repair pathways involved in cell death induced by heat shock. MATERIALS AND METHODS: B02, a specific inhibitor of human RAD51 (homologous recombination; HR), and NU7026, a specific inhibitor of DNA-PK (non-homologous end-joining; NHEJ), were used for survival assays of human cancer cell lines with different p53-gene status...
October 24, 2016: International Journal of Hyperthermia
Abhishek Bhattacherjee, Yuliya Hrynets, Mirko Betti
Fructosazine is a polyhydroxyalkylpyrazine recently reported to have antimicrobial activity against heat-resistant E. coli AW 1.7. This study investigated fructosazine's antimicrobial mechanism of action and compared it to that of riboflavin. Fructosazine-acetic acid was effective in permeabilizing the outer membrane based on an evaluation of bacterial membrane integrity using 1-N-phenyl-1-naphthylamine and propidium iodide. The uptake of fructosazine by E. coli was pH-dependent with a greater uptake at pH 5 compared to pH 7 for all times throughout 16 h, except 2, 3 and 10 h...
October 25, 2016: Journal of Agricultural and Food Chemistry
Qi Zhang, Zhongduo Wang, Feng Hou, Rachel Harding, Xinyi Huang, Aiping Dong, John R Walker, Yufeng Tong
BACKGROUND: Seven in absentia homologs (SIAHs) comprise a family of highly conserved E3 ubiquitin ligases that play an important role in regulating signalling pathways in tumorigenesis, including the DNA damage repair and hypoxia response pathways. SIAH1 and SIAH2 have been found to function as a tumour repressor and a proto-oncogene, respectively, despite the high sequence identity of their substrate binding domains (SBDs). Ubiquitin-specific protease USP19 is a deubiquitinase that forms a complex with SIAHs and counteracts the ligase function...
October 21, 2016: Biochimica et Biophysica Acta
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