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mitochondrial damage

Kolla Rajasekhar, Kapilkumar Mehta, Thimmaiah Govindaraju
Amyloid beta (Aβ) aggregation is the key trait responsible for the pathological devastation caused by Alzheimer's disease (AD). Among the various pathways of multifaceted toxicity exhibited by Aβ aggregates in neuronal cells, generation of reactive oxygen species (ROS) by Aβ-CuII complex and mitochondrial damage are prominent. Aβ interferes with mitochondrial transport channels, causing mitochondrial dysfunction. Herein, we present nontoxic hybrid multifunctional modulators (HMMs, TGR86-88) developed by integrating the structural and functional features of the metal chelating aggregation modulator, clioquinol (Clq) and the antioxidant epigallocatechin gallate (EGCG)...
March 20, 2018: ACS Chemical Neuroscience
Umar Muzaffer, V I Paul, Nagarajan Rajendra Prasad, Ramasamy Karthikeyan
The present study was aimed to investigate the photoprotective effect of the male flower of J. regia L. (MEJR) against ultraviolet-B induced apoptosis in human skin cells. Human skin epidermal keratinocytes were pretreated with the MEJR (80 µg/ml, has been selected after MTT assay), prior to 30 min UVB-irradiation at a dose of 20 mJ/cm2 . Mitochondrial membrane potential was evaluated using Rhodamine-123 staining; the % apoptosis by Hoechst staining and acridine orange staining; DNA damage was measured by comet assay...
March 2018: Biochemistry and Biophysics Reports
Victoria Pons, Joan Riera, Xavier Capó, Miquel Martorell, Antoni Sureda, Josep A Tur, Franchek Drobnic, Antoni Pons
Background: Caloric restriction induces mitochondrial biogenesis and improves physical fitness in rodents. We aimed to provide evidence of how caloric restriction affects the body composition and physical performance of trained athletes and to evaluate the possible impact of an every-other-day feeding diet on nutritional deficiencies of micronutrients and essential fatty acids. Methods: The study was performed with 12 healthy male athletes by carrying out a 33% caloric restriction with respect to their usual diet...
2018: Journal of the International Society of Sports Nutrition
Lifen Xie, Xiaolan Feng, Yin Shi, Meng He, Pan Wang, Xiaobing Wang, Zeyuan Mi, Quanhong Liu, Kun Zhang
Inhibition of the increased aerobic glycolysis in cancer cells is a promising methodology for various malignant tumor therapies but is limited by systemic toxicity, at least in part. Recent studies suggest that dual restriction of glycolysis and mitochondrial function may overcome this issue. Sonodynamic therapy (SDT), a prospective therapeutic modality for cancers, has been reported to induce mitochondria-dependent cell damage. Here, we investigated the combined effect of SDT and 2-deoxyglucose (2DG), an anti-glycolytic agent, on breast cancer both in vitro and in vivo...
March 16, 2018: Ultrasound in Medicine & Biology
Shuyi Wang, Jun Ren
Alcoholism is accompanied with a high incidence of cardiac morbidity and mortality due to the development of alcoholic cardiomyopathy, manifested as dilation of one or both ventricles, reduced ventricular wall thickness, myofibrillary disarray, interstitial fibrosis, hypertrophy and contractile dysfunction. Several theories have been postulated for the etiology of alcoholic cardiomyopathy including ethanol/acetaldehyde toxicity, mitochondrial production of reactive oxygen species, oxidative injury, apoptosis, impaired myofilament Ca2+ sensitivity and protein synthesis, altered fatty acid extraction and deposition, as well as accelerated protein catabolism...
March 16, 2018: Biochimica et Biophysica Acta
Priya Goswami, Subhabrata Paul, Ritesh Banerjee, Rita Kundu, Anita Mukherjee
Betulinic acid (BA) is a naturally occurring terpenoid found principally in the bark of birch trees as well as in numerous other plants. BA is reported to inhibit cancer progression and induce apoptosis in multiple tumor types. In the present study we have investigated the cytotoxicity and potential genotoxicity of BA in SiHa cells. The cell viability was measured by using MTT assay and the morphological changes, DNA damage, changes in cell cycle and mitochondrial membrane potential (MMP) were used for the assessment of apoptosis...
April 2018: Mutation Research
Susana Braz-Mota, Derek F Campos, Tyson J MacCormack, Rafael M Duarte, Adalberto L Val, Vera M F Almeida-Val
Copper oxide nanoparticles (nCuO) are widely used in boat antifouling paints and are released into the environment, potentially inducing toxicity to aquatic organisms. The present study aimed to understand the effects of nCuO and dissolved copper (Cu) on two ornamental Amazon fish species: dwarf cichlid (Apistogramma agassizii) and cardinal tetra (Paracheirodon axelrodi). Fish were exposed to 50% of the LC50 for nCuO (dwarf cichlid 58.31μgL-1 and cardinal tetra 69.6μgL-1 ) and Cu (dwarf cichlid 20μgL-1 and cardinal tetra 22...
March 1, 2018: Science of the Total Environment
Noelia Morales-Prieto, Julia Ruiz-Laguna, David Sheehan, Nieves Abril
The use of DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane) in some countries, although regulated, is contributing to an increased worldwide risk of exposure to this organochlorine pesticide or its derivative p,p'-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene]. Many studies have associated p,p'-DDE exposure to type 2 diabetes, obesity and alterations of the reproductive system, but their molecular mechanisms of toxicity remain poorly understood. We have addressed this issue by using commercial microarrays based on probes for the entire Mus musculus genome to determine the hepatic transcriptional signatures of p,p'-DDE in the phylogenetically close mouse species Mus spretus...
March 16, 2018: Environmental Pollution
JinYing Liu, Xiaokang Liu, Wei Ma, Wei Kou, CaiLi Li, Jin Zhao
PURPOSE: Ovarian cancer is one of the deadly causes of gynecological cancer related mortality worldwide. Despite initial responses to chemotherapy, the disease consistently relapses. Therefore there is an urgent need for identification of anticancer lead molecules for treatment and management of ovarian cancer. The present study evaluated the anticancer activity of cucurbitacin-A on ovarian SKVO3 cancer cells. METHODS: The cell viability of SKVO3 cells was evaluated by MTT assay, while clonogenic assay was used to evaluate the effects on cancer cell colony formation...
January 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Chun-Hsiang Tan, Peter A McNaughton
The abilities to detect warmth and heat are critical for the survival of all animals, both in order to be able to identify suitable thermal environments for the many different activities essential for life and to avoid damage caused by extremes of temperature. Several ion channels belonging to the TRP family are activated by non-noxious warmth or by heat and are therefore plausible candidates for thermal detectors, but identifying those that actually regulate warmth and heat detection in intact animals has proven problematic...
March 19, 2018: Pflügers Archiv: European Journal of Physiology
Lu Sun, Zheng-Guo Cui, Shahbaz Ahmad Zakki, Qian-Wen Feng, Meng-Ling Li, Hidekuni Inadera
Hyperthermia is one therapeutic tool for damaging and killing cancer cells, with minimal injury to normal tissues. However, its cytotoxic effects alone are insufficient for quantitative cancer cell death. To overcome this limitation, several studies have explored non-toxic enhancers for hyperthermia-induced cell death. Capsaicin may be applicable as a therapeutic tool against various types of cancer. In the present study, we employed nonivamide, a less-pungent capsaicin analogue, to investigate its possible enhancing effects on hyperthermia-induced apoptosis; moreover, we analyzed its molecular mechanism...
March 15, 2018: Free Radical Biology & Medicine
Kate McArthur, Benjamin T Kile
The mitochondrial caspase cascade was originally thought to be required for apoptotic death driven by Bak/Bax-mediated intrinsic apoptosis. It has also been ascribed several 'non-apoptotic' functions, including differentiation, proliferation, and cellular reprogramming. Recent work has demonstrated that, during apoptosis, the caspase cascade suppresses damage-associated molecular pattern (DAMP)-initiated production of cytokines such as type I interferon by the dying cell. The caspase cascade is not required for death to occur; instead, it shapes the immunogenic properties of the apoptotic cell...
March 15, 2018: Trends in Cell Biology
Martyna Pakuła, Justyna Mikuła-Pietrasik, Łukasz Stryczyński, Paweł Uruski, Sebastian Szubert, Rafał Moszyński, Dariusz Szpurek, Stefan Sajdak, Andrzej Tykarski, Krzysztof Książek
Very little is known about the mechanisms by which malignant ascites modulates the cancer-promoting activity of human peritoneal mesothelial cells (HPMCs). Because malignant ascites induces pro-tumoral senescence in HPMCs, here we examined if this effect could be driven by oxidative stress. The study showed that malignant ascites generated by serous ovarian tumors induced oxidative damage to the DNA (γH2A.X, 53BP1, 8-hydroxy-2'-deoxyguanosine) and lipids (8-isoprostane) in HPMCs as well as increased the production of mitochondrial superoxides and cellular peroxides in these cells...
March 14, 2018: International Journal of Biochemistry & Cell Biology
Cheng Wang, Xianlin Han, Fang Liu, Tucker A Patterson, Joseph P Hanig, Merle G Paule, William Slikker
Adverse effects related to central nervous system (CNS) function in pediatric populations may, at times, be difficult, if not impossible to evaluate. Prolonged anesthetic exposure affects brain excitability and anesthesia during the most sensitive developmental stages and has been associated with mitochondrial dysfunction, aberrant lipid metabolism and synaptogenesis, subsequent neuronal damage, as well as long-term behavioral deficits. There has been limited research evaluating whether and how anesthetic agents affect cellular lipids, the most abundant components of the brain other than water...
March 14, 2018: Toxicology and Applied Pharmacology
Suzanne R Burstein, Hyun Jeong Kim, Jasmine A Fels, Liping Qian, Sheng Zhang, Ping Zhou, Anatoly A Starkov, Costantino Iadecola, Giovanni Manfredi
Recent evidence highlights a role for sex and hormonal status in regulating cellular responses to ischemic brain injury and neurodegeneration. A key pathological event in ischemic brain injury is the opening of a mitochondrial permeability transition pore (MPT) induced by excitotoxic calcium levels, which can trigger irreversible damage to mitochondria accompanied by the release of pro-apoptotic factors. However, sex differences in brain MPT modulation have not yet been explored. Here, we show that mitochondria isolated from female mouse forebrain have a lower calcium threshold for MPT than male mitochondria, and that this sex difference depends on the MPT regulator cyclophilin D (CypD)...
March 14, 2018: Biochimica et Biophysica Acta
Alfredo Briones-Herrera, Sabino Hazael Avila-Rojas, Omar Emiliano Aparicio-Trejo, Magdalena Cristóbal, Juan Carlos León-Contreras, Rogelio Hernández-Pando, Enrique Pinzón, José Pedraza-Chaverri, Laura Gabriela Sánchez-Lozada, Edilia Tapia
Maleic acid (MA)-induced nephropathy that is characterized by proteinuria, glycosuria, phosphaturia and a deficient urinary acidification and concentration. Sulforaphane (SF) is an indirect antioxidant that shows nephroprotective effects. The aim of the present work was to test the pre-treatment with SF against the MA-induced nephropathy. Wistar rats (230-260 g) were separated in the following groups: control, MA (which received 400 mg/kg of MA), SF + MA (which received MA and 1 mg/kg of SF each day for four days) and SF (which only received SF)...
March 13, 2018: Food and Chemical Toxicology
Maria Eugenia Sabatino, Ezequiel Grondona, Liliana D V Sosa, Bethania Mongi Bragato, Lucia Carreño, Virginia Juarez, Rodrigo A da Silva, Aline Remor, Lucila de Bortoli, Roberta de Paula Martins, Pablo A Pérez, Juan Pablo Petiti, Silvina Gutiérrez, Alicia I Torres, Alexandra Latini, Ana L De Paul
The cellular transformation of normal functional cells to neoplastic ones implies alterations in the cellular metabolism and mitochondrial function in order to provide the bioenergetics and growth requirements for tumour growth progression. Currently, the mitochondrial physiology and dynamic shift during pituitary tumour development are not well understood. Pituitary tumors present endocrine neoplastic benign growth which, in previous reports, we had shown that in addition to increased proliferation, these tumours were also characterized by cellular senescence signs with no indication of apoptosis...
March 13, 2018: Free Radical Biology & Medicine
Ana Isabel Padrão, Rita Nogueira-Ferreira, Rui Vitorino, Dulce Carvalho, Catarina Correia, Maria João Neuparth, Maria João Pires, Ana Isabel Faustino-Rocha, Lúcio Lara Santos, Paula Alexandra Oliveira, José Alberto Duarte, Daniel Moreira-Gonçalves, Rita Ferreira
Limiting cancer-induced cardiac damage has become an increasingly important issue to improve survival rates and quality of life. Exercise training has been shown to reduce cardiovascular complications in several diseases; however, its therapeutic role against cardiovascular consequences of cancer is in its infancy. In order to add new insights on the potential therapeutic effect of exercise training on cancer-related cardiac dysfunction, we used an animal model of urothelial carcinoma submitted to 13 weeks of treadmill exercise after 20 weeks of exposure to the carcinogenic N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)...
March 13, 2018: Archives of Biochemistry and Biophysics
Asmaa E Kassab, Ehab M Gedawy
As we are interested in synthetizing biologically active leads with dual anticancer and antibacterial activity, we adopted biology oriented drug synthesis (BIODS) strategy to synthesize a series of novel ciprofloxacin (CP) hybrids. The National Cancer Institute (USA) selected seventeen newly synthesized compounds for anticancer evaluation against 59 different human tumor cell lines. Five compounds 3e, 3f, 3h, 3o and 3p were further studied through determination of IC50 values against the most sensitive cancer cell lines...
March 9, 2018: European Journal of Medicinal Chemistry
Pan Pan, Hongmin Zhang, Longxiang Su, Xiaoting Wang, Dawei Liu
To explore the mechanism of mitochondrial uncoupling protein 2 (UCP2) mediating the protective of melatonin when septic cardiomyopathy. UCP2 knocked out mice and cardiomyocytes were used to study the effect of melatonin in response to LPS. Indicators of myocardial and mitochondria injury including mitochondrial membrane potential, mitochondrial permeability transition pore, calcium loading, ROS, and ATP detection were assessed. In addition cell viability and apoptosis as well as autophagy-associated proteins were evaluated...
March 16, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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