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Mitochondrial apoptosis

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https://www.readbyqxmd.com/read/27911443/transient-mitochondrial-dna-double-strand-breaks-in-mice-cause-accelerated-aging-phenotypes-in-a-ros-dependent-but-p53-p21-independent-manner
#1
Milena Pinto, Alicia M Pickrell, Xiao Wang, Sandra R Bacman, Aixin Yu, Aline Hida, Lloye M Dillon, Paul D Morton, Thomas R Malek, Siôn L Williams, Carlos T Moraes
We observed that the transient induction of mtDNA double strand breaks (DSBs) in cultured cells led to activation of cell cycle arrest proteins (p21/p53 pathway) and decreased cell growth, mediated through reactive oxygen species (ROS). To investigate this process in vivo we developed a mouse model where we could transiently induce mtDNA DSBs ubiquitously. This transient mtDNA damage in mice caused an accelerated aging phenotype, preferentially affecting proliferating tissues. One of the earliest phenotypes was accelerated thymus shrinkage by apoptosis and differentiation into adipose tissue, mimicking age-related thymic involution...
December 2, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27909249/mortalin-mediated-and-erk-controlled-targeting-of-hif-1%C3%AE-to-mitochondria-confers-resistance-to-apoptosis-under-hypoxia
#2
Ilias Mylonis, Maria Kourti, Martina Samiotaki, George Panayotou, George Simos
Hypoxia inducible factor-1 (HIF-1) is the main transcriptional activator of the cellular response to hypoxia and an important target of anticancer therapy. Phosphorylation by ERK stimulates the transcriptional activity of HIF-1α by inhibiting its CRM1-dependent nuclear export. Here, we demonstrate that phosphorylation by ERK also regulates the association of HIF-1α with a novel interaction partner identified as mortalin (GRP75) which mediates non-genomic involvement of HIF-1α in apoptosis. Mortalin binds specifically to HIF-1α lacking modification by ERK and their complex is localized outside the nucleus...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27909098/reversible-disruption-of-neuronal-mitochondria-by-ischemic-and-traumatic-injury-revealed-by-quantitative-two-photon-imaging-in-the-neocortex-of-anesthetized-mice
#3
Mikhail Kislin, Jeremy Sword, Ioulia V Fomitcheva, Deborah Croom, Evgeny Pryazhnikov, Eero Lihavainen, Dmytro Toptunov, Heikki Rauvala, Andre S Ribeiro, Leonard Khiroug, Sergei A Kirov
: Mitochondria play a variety of functional roles in cortical neurons, from metabolic support and neuroprotection to the release of cytokines that trigger apoptosis. In dendrites, mitochondrial structure is closely linked to their function, and fragmentation (fission) of the normally elongated mitochondria indicates loss of their function under such pathological conditions as stroke and brain trauma. Using in vivo two-photon microscopy in mouse brain, we quantified mitochondrial fragmentation in a full spectrum of cortical injuries ranging from severe to mild...
December 1, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27908776/3-geranyl-mono-substituted-chalcone-xanthoangelovl-induces-apoptosis-in-human-leukemia-k562%C3%A2-cells-via-activation-of-mitochondrial-pathway
#4
Yuou Teng, Lixin Wang, Huan Liu, Yuan Yuan, Qian Zhang, Meng Wu, Luyao Wang, Haomeng Wang, Zhen Liu, Peng Yu
3'-Geranyl-mono-substituted chalcone Xanthoangelol (1b), a chalcone derivative, was previously reported to show selective cytotoxicity against human chronic myelogenous leukemia K562 cells with a half-maximal inhibitory concentration (IC50) of 3.98 μM. In the present study, we investigated the molecular mechanism underlying the cytotoxicity of 1b in K562 cells. Treatment with compound 1b caused K562 cells to adopt a typical apoptotic morphology. Flow cytometric analysis also confirmed the presence of an apoptotic cell population following treatment of Annexin-V-FITC and propidium iodide (PI) double-labeled K562 cells with 1b...
November 28, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27908383/the-insecticide-spinosad-induces-dna-damage-and-apoptosis-in-hek293-and-hepg2-cells
#5
Mingjun Yang, Guanggang Xiang, Diqiu Li, Yang Zhang, Wenping Xu, Liming Tao
Spinosad, a pesticide acting on the central nervous system of insects, is classified as a pesticide with reduced risk. However, spinosad-induced toxicological effects on non-target organisms must not be ignored. This study aimed to evaluate the cytotoxicity and potential genotoxicity of spinosad in HEK293 and HepG2 cell lines. The results showed that spinosad caused a concentration- and time-dependent decrease in cell viability of HEK293 and HepG2 cells. Spinosad-induced p53 accumulation thereby upregulates the expression of Bax and downregulates the expression of Bcl-2...
December 2016: Mutation Research
https://www.readbyqxmd.com/read/27908232/iron-sulfur-clusters-in-mitochondrial-metabolism-multifaceted-roles-of-a-simple-cofactor
#6
REVIEW
Johnny Stiban, Minyoung So, Laurie S Kaguni
Iron-sulfur metabolism is essential for cellular function and is a key process in mitochondria. In this review, we focus on the structure and assembly of mitochondrial iron-sulfur clusters and their roles in various metabolic processes that occur in mitochondria. Iron-sulfur clusters are crucial in mitochondrial respiration, in which they are required for the assembly, stability, and function of respiratory complexes I, II, and III. They also serve important functions in the citric acid cycle, DNA metabolism, and apoptosis...
October 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27907185/antioxidant-antimicrobial-and-cytotoxic-properties-as-well-as-the-phenolic-content-of-the-extract-from-hancornia-speciosa-gomes
#7
Uilson P Santos, Jaqueline F Campos, Heron Fernandes V Torquato, Edgar Julian Paredes-Gamero, Carlos Alexandre Carollo, Leticia M Estevinho, Kely de Picoli Souza, Edson Lucas Dos Santos
Hancornia speciosa Gomes (Apocynaceae) is a fruit tree, popularly known as mangabeira, and it is widely distributed throughout Brazil. Several parts of the plant are used in folk medicine, and the leaf and bark extracts have anti-inflammatory, antihypertensive, antidiabetic, and antimicrobial properties. In this study, we investigated the chemical composition of the ethanolic extract of Hancornia speciosa leaves (EEHS) and its antioxidant, antimicrobial, and cytotoxic activities as well as the mechanisms involved in cell death...
2016: PloS One
https://www.readbyqxmd.com/read/27905569/shikonin-induces-mitochondria-mediated-apoptosis-and-enhances-chemotherapeutic-sensitivity-of-gastric-cancer-through-reactive-oxygen-species
#8
Wenquan Liang, Aizhen Cai, Guozhu Chen, Hongqing Xi, Xiaosong Wu, Jianxin Cui, Kecheng Zhang, Xudong Zhao, Jiyun Yu, Bo Wei, Lin Chen
The prognosis of gastric cancer remains poor due to clinical drug resistance. Novel drugs are urgently needed. Shikonin (SHK), a natural naphthoquinone, has been reported to trigger cell death and overcome drug resistance in anti-tumour therapy. In this study, we investigated the effectiveness and molecular mechanisms of SHK in treatment with gastric cancer. In vitro, SHK suppresses proliferation and triggers cell death of gastric cancer cells but leads minor damage to gastric epithelial cells. SHK induces the generation of intracellular reactive oxygen species (ROS), depolarizes the mitochondrial membrane potential (MMP) and ultimately triggers mitochondria-mediated apoptosis...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905446/genomic-evolution-and-chemoresistance-in-germ-cell-tumours
#9
Amaro Taylor-Weiner, Travis Zack, Elizabeth O'Donnell, Jennifer L Guerriero, Brandon Bernard, Anita Reddy, G Celine Han, Saud AlDubayan, Ali Amin-Mansour, Steven E Schumacher, Kevin Litchfield, Clare Turnbull, Stacey Gabriel, Rameen Beroukhim, Gad Getz, Scott L Carter, Michelle S Hirsch, Anthony Letai, Christopher Sweeney, Eliezer M Van Allen
Germ-cell tumours (GCTs) are derived from germ cells and occur most frequently in the testes. GCTs are histologically heterogeneous and distinctly curable with chemotherapy. Gains of chromosome arm 12p and aneuploidy are nearly universal in GCTs, but specific somatic genomic features driving tumour initiation, chemosensitivity and progression are incompletely characterized. Here, using clinical whole-exome and transcriptome sequencing of precursor, primary (testicular and mediastinal) and chemoresistant metastatic human GCTs, we show that the primary somatic feature of GCTs is highly recurrent chromosome arm level amplifications and reciprocal deletions (reciprocal loss of heterozygosity), variations that are significantly enriched in GCTs compared to 19 other cancer types...
November 30, 2016: Nature
https://www.readbyqxmd.com/read/27904736/the-biology-behind-b-cell-lymphoma-2-as-a-target-in-chronic-lymphocytic-leukemia
#10
REVIEW
Valentín Ortíz-Maldonado, Pablo Mozas, Julio Delgado
B-cell lymphoma 2 (BCL2)-type proteins are key regulators of the intrinsic or mitochondrial pathway for apoptosis. Since escape from apoptosis is one the main 'hallmarks of cancer', BCL2 inhibitors have emerged as promising therapeutic agents for diverse lymphoid malignancies, particularly chronic lymphocytic leukemia (CLL). Multiple clinical trials have shown efficacy of these agents in patients with relapsed/refractory disease with a favorable toxicity profile. Moreover, some clinical trials indicate that combination with monoclonal antibodies and other novel agents may enhance their effect...
December 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27904697/inhibitory-effect-of-bufalin-on-retinoblastoma-cells-hxo-rb44-via-the-independent-mitochondrial-and-death-receptor-pathway
#11
Qingfeng Meng, Yan Zhao, LiXin An, Xia Li, Ping Liu
Cinobufacini (Huachansu) is a Chinese medicine prepared from the skin of Bufo bufo gargarizans Cantor (Bufonidae), and has long been used in traditional Chinese medicine. In the present study, the anti-retinoblastoma constituent bufalin obtained from Cinobufacini was investigated. Treatment of human retinoblastoma (HXO-RB44) cells with bufalin induced apoptosis which was accompanied by a decrease in mitochondrial membrane potential, activation of caspase-9, caspase-8 and caspase-3, as well as changes in the expression of cytochrome C...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27904667/icaritin-induces-apoptotic-and-autophagic-cell-death-in-human-glioblastoma-cells
#12
Zhaopei Li, Xiangwen Meng, Lin Jin
BACKGROUND: GBM represents the most aggressive type of glioma which is featured by extremely aggressive invasion and destructive malignancy with a high proliferation rate. The aim of this study was to investigate the in vitro anti-tumor effect of icaritin in human GBM cell line U87. METHODS: The effect of icaritin on In vitro cell viability was determined by MTT assay and colony formation assay. The inducing effect of icaritin on cell cycle arrest, mitochondrial membrane potential loss, apoptosis, autophagy and intracellular ROS generation was assessed by flow cytometry...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27904474/poly-adp-ribose-polymerase-inhibition-reveals-a-potential-mechanism-to-promote-neuroprotection-and-treat-neuropathic-pain
#13
REVIEW
Prashanth Komirishetty, Aparna Areti, Ranadeep Gogoi, Ramakrishna Sistla, Ashutosh Kumar
Neuropathic pain is triggered by the lesions to peripheral nerves which alter their structure and function. Neuroprotective approaches that limit the pathological changes and improve the behavioral outcome have been well explained in different experimental models of neuropathy but translation of such strategies to clinics has been disappointing. Experimental evidences revealed the role of free radicals, especially peroxynitrite after the nerve injury. They provoke oxidative DNA damage and consequent over-activation of the poly(ADP-ribose) polymerase (PARP) upregulates pro-inflammatory pathways, causing bioenergetic crisis and neuronal death...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27902770/mitochondrial-targeted-decyl-triphenylphosphonium-enhances-2-deoxy-d-glucose-mediated-oxidative-stress-and-clonogenic-killing-of-multiple-myeloma-cells
#14
Jeanine Schibler, Ann M Tomanek-Chalkley, Jessica L Reedy, Fenghuang Zhan, Douglas R Spitz, Michael K Schultz, Apollina Goel
Therapeutic advances have markedly prolonged overall survival in multiple myeloma (MM) but the disease currently remains incurable. In a panel of MM cell lines (MM.1S, OPM-2, H929, and U266), using CD138 immunophenotyping, side population staining, and stem cell-related gene expression, we demonstrate the presence of stem-like tumor cells. Hypoxic culture conditions further increased CD138low stem-like cells with upregulated expression of OCT4 and NANOG. Compared to MM cells, these stem-like cells maintained lower steady-state pro-oxidant levels with increased uptake of the fluorescent deoxyglucose analog...
2016: PloS One
https://www.readbyqxmd.com/read/27901621/perfluorooctanoic-acid-induces-mitochondrial-dysfunction-in-mc3t3-e1-osteoblast-cells
#15
Eun Mi Choi, Kwang Sik Suh, Sang Youl Rhee, Seungjoon Oh, Jeong-Taek Woo, Sung Woon Kim, Young Seol Kim, Youngmi Kim Pak, Suk Chon
Perfluorooctanoic acid (PFOA), a stable organic perfluorinated compound, is an emerging persistent organic pollutant, found widely in human and wildlife populations. Recent evidence suggests that exposure to environmental toxicants can be associated with higher risks of osteoporosis and fractures. We studied the cellular toxicology of PFOA in MC3T3-E1osteoblast cells. To examine the effect of PFOA, we measured cell viability, reactive oxygen species (ROS), mitochondrial superoxide, and mitochondrial parameters including adenosine triphosphate (ATP) level, mitochondrial membrane potential (MMP), cardiolipin content, and cytochrome c release in MC3T3-E1 cells...
November 30, 2016: Journal of Environmental Science and Health. Part A, Toxic/hazardous Substances & Environmental Engineering
https://www.readbyqxmd.com/read/27901126/low-level-light-treatment-ameliorates-immune-thrombocytopenia
#16
Jingke Yang, Qi Zhang, Peiyu Li, Tingting Dong, Mei X Wu
Immune thrombocytopenia (ITP) is an immune-mediated acquired bleeding disorder characterized by abnormally low platelet counts. We reported here the ability of low-level light treatment (LLLT) to alleviate ITP in mice. The treatment is based on noninvasive whole body illumination 30 min a day for a few consecutive days by near infrared light (830 nm) transmitted by an array of light-emitting diodes (LEDs). LLLT significantly lifted the nadir of platelet counts and restored tail bleeding time when applied to two passive ITP models induced by anti-CD41 antibody...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27901051/mycobacterium-avium-mav2054-protein-induces-macrophage-apoptosis-by-targeting-mitochondria-and-reduces-intracellular-bacterial-growth
#17
Kang-In Lee, Jake Whang, Han-Gyu Choi, Yeo-Jin Son, Haet Sal Jeon, Yong Woo Back, Hye-Soo Park, Seungwha Paik, Jeong-Kyu Park, Chul Hee Choi, Hwa-Jung Kim
Mycobacterium avium complex induces macrophage apoptosis. However, the M. avium components that inhibit or trigger apoptosis and their regulating mechanisms remain unclear. We recently identified the immunodominant MAV2054 protein by fractionating M. avium culture filtrate protein by multistep chromatography; this protein showed strong immuno-reactivity in M. avium complex pulmonary disease and in patients with tuberculosis. Here, we investigated the biological effects of MAV2054 on murine macrophages. Recombinant MAV2054 induced caspase-dependent macrophage apoptosis...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27900015/celastrol-negatively-regulates-cell-invasion-and-migration-ability-of-human-osteosarcoma-via-downregulation-of-the-pi3k-akt-nf-%C3%AE%C2%BAb-signaling-pathway-in-vitro
#18
Xiaolong Yu, Qiang Wang, Xin Zhou, Changlin Fu, Ming Cheng, Runsheng Guo, Hucheng Liu, Bin Zhang, Min Dai
Osteosarcoma (OS) is a primary malignant tumor of the bone, with a tendency to metastasize early. Despite the advances in treatment options, more than 30% of patients develop distant metastases, and the prognosis of these patients with metastases is extremely poor. Celastrol has been demonstrated to manifest multiple pharmacological activities, including induction of apoptosis in numerous types of cancer cell lines. Our previous studies have also suggested that Celastrol is capable of inducing apoptosis of human osteosarcoma cells via the mitochondrial-dependent pathway...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899290/didymin-induces-apoptosis-through-mitochondrial-dysfunction-and-up-regulation-of-rkip-in-human-hepatoma-cells
#19
Jinbin Wei, Quanfang Huang, Facheng Bai, Jun Lin, Jinlan Nie, Shengjuan Lu, Chunyuang Lu, Renbin Huang, Zhongpeng Lu, Xing Lin
In the present study, a flavonoid was isolated from Origanum vulgare and identified as didymin. The effect and mechanism of O. vulgare didymin (OVD) on human HepG2 liver carcinoma cell was then assessed. Our results showed that OVD strongly inhibited the viability, clonogenicity and migration of HepG2 cells. OVD significantly induced apoptosis and induced cell cycle arrest at G2/M phase by regulating cyclin B1, cyclin D1 and CDK4. The anti-proliferative and pro-apoptotic effects were associated with changes in the Bcl-2/Bax ratio and induction of caspase-mediated apoptosis...
November 26, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27898051/preparation-of-6-8-11-amino-chloro-oxoisoaporphine-and-group-10-metal-complexes-and-evaluation-of-their-in-vitro-and-in-vivo-antitumor-activity
#20
Qi-Pin Qin, Jiao-Lan Qin, Ting Meng, Gui-Ai Yang, Zu-Zhuang Wei, Yan-Cheng Liu, Hong Liang, Zhen-Feng Chen
A series of group-10 metal complexes 1-14 of oxoisoaporphine derivatives were designed and synthesized. 1-14 were more selectively cytotoxic to Hep-G2 cells comparing with normal liver cells. In vitro cytotoxicity results showed that complexes 1-6, 7, 8, 10 and 11, especially 3, were telomerase inhibitors targeting c-myc, telomeric, and bcl-2 G4s and triggered cell senescence and apoptosis; they also caused telomere/DNA damage and S phase arrest. In addition, 1-6 also caused mitochondrial dysfunction. Notably, 3 with 6-amino substituted ligand L(a) exhibited less side effects than 6 with 8-amino substituted ligand L(b) and cisplatin, but similar tumor growth inhibition efficacy in BEL-7402 xenograft model...
November 29, 2016: Scientific Reports
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