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https://www.readbyqxmd.com/read/28346428/autophagy-is-required-for-cell-survival-under-l-asparaginase-induced-metabolic-stress-in-acute-lymphoblastic-leukemia-cells
#1
H Takahashi, J Inoue, K Sakaguchi, M Takagi, S Mizutani, J Inazawa
L-asparaginase has been used for more than three decades in acute lymphoblastic leukemia (ALL) patients and remains an essential drug in the treatment of ALL. Poor response to L-asparaginase is associated with increased risk of therapeutic failure in ALL. However, both the metabolic perturbation and molecular context of L-asparaginase-treated ALL cells has not been fully elucidated. Here we identify that treatment with L-asparaginase results in metabolic shutdown via the reduction of both glycolysis and oxidative phosphorylation, accompanied by mitochondrial damage and activation of autophagy...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28345606/53bp1-contributes-to-regulation-of-autophagic-clearance-of-mitochondria
#2
Cha Kyung Youn, Hong Beum Kim, Ting Ting Wu, Sanggon Park, Sung Il Cho, Jung-Hee Lee
Autophagy, the primary recycling pathway within cells, plays a critical role in mitochondrial quality control under normal growth conditions and in the cellular response to stress. Here we provide evidence that 53BP1, a DNA damage response protein, is involved in regulating mitochondrial clearance from the cell via a type of autophagy termed mitophagy. We found that when either human or mouse cells were 53BP1-deficient, there was an increase in mitochondrial abnormalities, as observed through staining intensity, aggregation, and increased mass...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28344907/grape-seed-proanthocyanidin-extract-protects-lymphocytes-against-histone-induced-apoptosis
#3
Ping Chang, Bing Mo, David M Cauvi, Ying Yu, Zhenhui Guo, Jian Zhou, Qiong Huang, Qitao Yan, Guiming Chen, Zhanguo Liu
Apoptosis of lymphocytes is associated with immunosuppression and poor prognosis in sepsis. Our previous report showed that histones, nuclear proteins released from damaged or dying cells in sepsis, can mediate lymphocyte apoptosis via mitochondria damage. Grape seed proanthocyanidin extract (GSPE), a natural substance with protective properties against oxidative stress, plays a vital role in cell and mitochondria protection. We thus hypothesized that GSPE may play a protective role in histone-induced lymphocyte apoptosis through its anti-oxidative properties...
2017: PeerJ
https://www.readbyqxmd.com/read/28343311/mechanistic-insight-of-platelet-apoptosis-leading-to-non-surgical-bleeding-among-heart-failure-patients-supported-by-continuous-flow-left-ventricular-assist-devices
#4
Nandan K Mondal, Tielou Li, Zengsheng Chen, Hegang H Chen, Erik N Sorensen, Si M Pham, Michael A Sobieski, Steven C Koenig, Mark S Slaughter, Bartley P Griffith, Zhongjun J Wu
Non-surgical bleeding (NSB) is the most common clinical complication in heart failure (HF) patients supported by continuous-flow left ventricular assist devices (CF-LVADs). In this study, oxidative stress and alteration of signal pathways leading to platelet apoptosis were investigated. Thirty-one HF patients supported by CF-LVADs were divided into bleeder (n = 12) and non-bleeder (n = 19) groups. Multiple blood samples were collected at pre-implant (baseline) and weekly up to 1-month post-implant. A single blood sample was collected from healthy subjects (reference)...
March 25, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28342966/time-courses-of-post-injury-mitochondrial-oxidative-damage-and-respiratory-dysfunction-and-neuronal-cytoskeletal-degradation-in-a-rat-model-of-focal-traumatic-brain-injury
#5
Rachel L Hill, Indrapal N Singh, Juan A Wang, Edward D Hall
Traumatic brain injury (TBI) results in rapid reactive oxygen species (ROS) production and oxidative damage to essential brain cellular components leading to neuronal dysfunction and cell death. It is increasingly appreciated that a major player in TBI-induced oxidative damage is the reactive nitrogen species (RNS) peroxynitrite (PN) which is produced in large part in injured brain mitochondria. Once formed, PN decomposes into highly reactive free radicals that trigger membrane lipid peroxidation (LP) of polyunsaturated fatty acids (e...
March 23, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28342871/oxidative-damage-induces-apoptosis-and-promotes-calcification-in-disc-cartilage-endplate-cell-through-ros-mapk-nf-%C3%AE%C2%BAb-pathway-implications-for-disc-degeneration
#6
Yingchao Han, Xinhua Li, Meijun Yan, Mingjie Yang, Shanjin Wang, Jie Pan, Lili Jun, Jun Tan
Cartilage endplate (CEP) cell calcification and apoptosis play a vital role in the intervertebral disc degeneration (IVDD). Oxidative stress is a key factor in inducing programmed cell death and cartilage calcification. However, the cell death and calcification of cartilage endplate cells under oxidative stress have never been described. The present study investigated the apoptosis and calcification in the cartilage endplate cell under oxidative stress induced by H2O2 to understand the underlying mechanism of IVDD...
March 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28342806/molecular-regulation-of-mitochondrial-dynamics-in-cardiac-disease
#7
REVIEW
Jinliang Nan, Wei Zhu, M S Rahman, Mingfei Liu, Dan Li, Shengan Su, Na Zhang, Xinyang Hu, Hong Yu, Mahesh P Gupta, Jian''an Wang
Mitochondrial homeostasis is critical for keeping functional heart in response to metabolic or environmental stresses. Mitochondrial fission and fusion (mitochondrial dynamics) play essential roles in maintaining mitochondrial homeostasis, defects in mitochondrial dynamics lead to cardiac diseases such as ischemia-reperfusion injury (IRI), heart failure and diabetic cardiomyopathy. Mitochondrial dynamics is determined by mitochondrial fission and fusion proteins, including OPA1, mitofusins and Drp1. These proteins are tightly regulated by a series of signaling pathways through different aspects such as transcription, post translation modifications (PTMs) and proteasome-dependent protein degradation...
March 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28342615/effect-of-increasing-body-condition-on-oxidative-stress-and-mitochondrial-biogenesis-in-subcutaneous-adipose-tissue-depot-of-nonlactating-dairy-cows
#8
L Laubenthal, L Ruda, N Sultana, J Winkler, J Rehage, U Meyer, S Dänicke, H Sauerwein, S Häussler
With the onset of lactation, dairy cows with a body condition score >3.5 are sensitive to oxidative stress and metabolic disorders. Adipose tissue (AT) can adapt to varying metabolic demands and energy requirements by the plasticity of its size during lactation. In AT, angiogenesis is necessary to guarantee sufficient oxygen and nutrient supply for adipocytes. Cellular energy metabolism is reflected mainly by mitochondria, which can be quantified by the mitochondrial DNA copy number per cell. In the present study, we aimed to investigate the effect of overconditioning on angiogenesis and mitochondrial biogenesis in AT of nonlactating cows, irrespective of the physiological influences of lactation and pregnancy...
March 22, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28341246/anemone-rivularis-inhibits-pyruvate-dehydrogenase-kinase-activity-and-tumor-growth
#9
Tae-Wook Chung, Jeong-Hee Lee, Hee-Jung Choi, Mi-Ju Park, Eun-Yeong Kim, Sebok Jang, Syng-Ook Lee, Sang Woo Lee, Jin Hang, Li Wan Yi, Ki-Tae Ha
ETHNOPHAMACOLOGICAL RELEVANCE: Anemone rivularis Buch.-Ham. ex DC. (Ranunculaceae) have been used as a traditional remedy for treatment of inflammation and cancer. However, there is no report demonstrating experimental evidence on anti-tumor action of A. rivularis. AIM OF STUDY: The Warburg's effect, preference of aerobic glycolysis rather than oxidative phosphorylation (OXPHOS) even in oxygen rich condition, is focused as one of major characteristics of malignant tumor...
March 21, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28339958/postconditioning-protects-renal-fibrosis-by-attenuating-oxidative-stress-induced-mitochondrial-injury
#10
Shuxian Zhang, Xiaohua Tan, Yan Chen, Xiuying Zhang
Background.: Epithelial-mesenchymal transition (EMT) plays a critical role in renal fibrosis. We hypothesize that mitochondrial DNA damage and DNA deletions caused by reactive oxygen species (ROS) during renal ischemia-reperfusion injury (IRI) might lead to EMT in renal fibrosis. Methods.: Rats were classified into seven groups: sham-operation, IRI, postconditioning (POC), I/R + apocynin, POC +  apocynin, I/R + Mito-Tempol (Mito-T) and POC +  Mito-T...
March 3, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28338610/fructose-rich-diet-affects-mitochondrial-dna-damage-and-repair-in-rats
#11
Federica Cioffi, Rosalba Senese, Pasquale Lasala, Angela Ziello, Arianna Mazzoli, Raffaella Crescenzo, Giovanna Liverini, Antonia Lanni, Fernando Goglia, Susanna Iossa
Evidence indicates that many forms of fructose-induced metabolic disturbance are associated with oxidative stress and mitochondrial dysfunction. Mitochondria are prominent targets of oxidative damage; however, it is not clear whether mitochondrial DNA (mtDNA) damage and/or its lack of repair are events involved in metabolic disease resulting from a fructose-rich diet. In the present study, we evaluated the degree of oxidative damage to liver mtDNA and its repair, in addition to the state of oxidative stress and antioxidant defense in the liver of rats fed a high-fructose diet...
March 24, 2017: Nutrients
https://www.readbyqxmd.com/read/28337983/self-inflicted-dna-double-strand-breaks-sustain-tumorigenicity-and-stemness-of-cancer-cells
#12
Xinjian Liu, Fang Li, Qian Huang, Zhengxiang Zhang, Ling Zhou, Yu Deng, Min Zhou, Donald E Fleenor, He Wang, Michael B Kastan, Chuan-Yuan Li
DNA double-strand breaks (DSBs) are traditionally associated with cancer through their abilities to cause chromosomal instabilities or gene mutations. Here we report a new class of self-inflicted DNA DSBs that can drive tumor growth irrespective of their effects on genomic stability. We discover a mechanism through which cancer cells cause DSBs in their own genome spontaneously independent of reactive oxygen species or replication stress. In this mechanism, low-level cytochrome c leakage from the mitochondria leads to sublethal activation of apoptotic caspases and nucleases, which causes DNA DSBs...
March 24, 2017: Cell Research
https://www.readbyqxmd.com/read/28337542/%C3%AE-synuclein-binds-to-the-er-mitochondria-tethering-protein-vapb-to-disrupt-ca-2-homeostasis-and-mitochondrial-atp-production
#13
Sébastien Paillusson, Patricia Gomez-Suaga, Radu Stoica, Daniel Little, Paul Gissen, Michael J Devine, Wendy Noble, Diane P Hanger, Christopher C J Miller
α-Synuclein is strongly linked to Parkinson's disease but the molecular targets for its toxicity are not fully clear. However, many neuronal functions damaged in Parkinson's disease are regulated by signalling between the endoplasmic reticulum (ER) and mitochondria. This signalling involves close physical associations between the two organelles that are mediated by binding of the integral ER protein vesicle-associated membrane protein-associated protein B (VAPB) to the outer mitochondrial membrane protein, protein tyrosine phosphatase-interacting protein 51 (PTPIP51)...
March 23, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28337125/neuronal-mitophagy-in-neurodegenerative-diseases
#14
REVIEW
Marta Martinez-Vicente
Neuronal homeostasis depends on the proper functioning of different quality control systems. All intracellular components are subjected to continuous turnover through the coordinated synthesis, degradation and recycling of their constituent elements. Autophagy is the catabolic mechanism by which intracellular cytosolic components, including proteins, organelles, aggregates and any other intracellular materials, are delivered to lysosomes for degradation. Among the different types of selective autophagy described to date, the process of mitophagy involves the selective autophagic degradation of mitochondria...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28333383/calcium-transport-and-signaling-in-mitochondria
#15
Roberto Bravo-Sagua, Valentina Parra, Camila López-Crisosto, Paula Díaz, Andrew F G Quest, Sergio Lavandero
Calcium (Ca2+) is a key player in the regulation of many cell functions. Just like Ca2+, mitochondria are ubiquitous, versatile, and dynamic players in determining both cell survival and death decisions. Given their ubiquitous nature, the regulation of both is deeply intertwined, whereby Ca2+ regulates mitochondrial functions, while mitochondria shape Ca2+ dynamics. Deregulation of either Ca2+ or mitochondrial signaling leads to abnormal function, cell damage or even cell death, thereby contributing to muscle dysfunction or cardiac pathologies...
March 16, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28331313/involvement-of-pink1-parkin-mediated-mitophagy-in-zno-nanoparticle-induced-toxicity-in-bv-2-cells
#16
Limin Wei, Jianfeng Wang, Aijie Chen, Jia Liu, Xiaoli Feng, Longquan Shao
With the increasing application of zinc oxide nanoparticles (ZnO NPs) in biological materials, the neurotoxicity caused by these particles has raised serious concerns. However, the underlying molecular mechanisms of the toxic effect of ZnO NPs on brain cells remain unclear. Mitochondrial damage has been reported to be a factor in the toxicity of ZnO NPs. PINK1/parkin-mediated mitophagy is a newly emerging additional function of autophagy that selectively degrades impaired mitochondria. Here, a PINK1 gene knockdown BV-2 cell model was established to determine whether PINK1/parkin-mediated mitophagy was involved in ZnO NP-induced toxicity in BV-2 cells...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28329820/hepatocellular-toxicity-of-imidazole-and-triazole-antimycotic-agents
#17
Patrizia Haegler, Lorenz Joerin, Stephan Krähenbühl, Jamal Bouitbir
Hepatotoxicity has been described for all antimycotic azoles currently marketed. A possible mechanism involving mitochondrial dysfunction has been postulated for ketoconazole, but not for the other azoles. The aim of the current investigations was to study the toxicity of different azoles in human cell models and to find out mechanisms of their toxicity. In HepG2 cells, posaconazole and ketoconazole were cytotoxic starting at 20 and 50 µM and decreased the cellular ATP content starting at 5 and 10 µM, respectively...
January 27, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28328544/non-toxic-fluorescent-phosphonium-probes-to-detect-mitochondrial-potential
#18
Ana Šarić, Ivo Crnolatac, Frédéric Bouillaud, Sandra Sobočanec, Ana-Matea Mikecin, Željka Mačak Šafranko, Todor Delgeorgiev, Ivo Piantanida, Tihomir Balog, Patrice X Petit
We evaluated our phosphonium-based fluorescent probes for selective staining of mitochondria. Currently used probes for monitoring mitochondrial membrane potential show varying degrees of interference with cell metabolism, photo-induced damage and probe binding. Here presented probes are characterised by highly efficient cellular uptake and specific accumulation in mitochondria. Fluorescent detection of the probes was accomplished using flow cytometry and confocal microscopy imaging of yeast and mammalian cells...
March 22, 2017: Methods and Applications in Fluorescence
https://www.readbyqxmd.com/read/28324492/detection-of-hypoxia-induced-and-iron-depletion-induced-mitophagy-in-mammalian-cells
#19
Shun-Ichi Yamashita, Tomotake Kanki
Mitochondrial quality and quantity are not only regulated by mitochondrial fusion and fission but also by mitochondria degradation. Mitophagy, an autophagy specific for damaged or unnecessary mitochondria, is believed to be an important pathway for mitochondrial homeostasis. To date, several stimuli are known to induce mitophagy. Some of these stimuli, however, including hypoxia, iron depletion, and nitrogen starvation, induce mild mitophagy, which is difficult to detect through decreased mitochondrial mass...
March 22, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28324490/assessment-of-mitophagy-in-ips-cell-derived-neurons
#20
Kei-Ichi Ishikawa, Akihiro Yamaguchi, Hideyuki Okano, Wado Akamatsu
Aberrant mitochondrial function is associated with many neurological diseases. Mitophagy is a key mechanism for the elimination of damaged mitochondria and maintenance of mitochondrial homeostasis. Induced pluripotent stem (iPS) cell technologies developed over the last decade have allowed us to analyze functions of the human neuron. Here we describe an efficient induction method from human iPS cells to neurons, followed by an image-based mitophagy assay.
March 22, 2017: Methods in Molecular Biology
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