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mitochondrial and baf

Yun Sun, Yingfeng Zheng, Chunxiao Wang, Yizhi Liu
Glutathione (GSH) protects against oxidative damage in many tissues, including retinal pigment epithelium (RPE). Oxidative stress-mediated senescence and death of RPE and subsequent death of photoreceptors have been observed in age-related macular degeneration (AMD). Although the consequences of GSH depletion have been described previously, questions remain regarding the molecular mechanisms. We herein examined the downstream effects of GSH depletion on stress-induced premature senescence (SIPS) and cell death in human RPE cells...
July 9, 2018: Cell Death & Disease
Xin-Yu Bai, Yuan-Gui Liu, Wu Song, Ying-Ying Li, Dong-Shun Hou, Hao-Ming Luo, Ping Liu
OBJECTIVES: To investigate the antitumour property of tetrandrine by inducing autophagy and apoptosis in human gastric cancer cells, and to explore the potential molecular mechanisms. METHODS: The antitumour activity of tetrandrine was assessed through MTT assay. Apoptosis was measured by flow cytometry and microscopic examination of cellular morphology. The mitochondrial membrane potential was detected by staining with Rh-123. Induction of autophagy was monitored by transmission electron microscopy observation, using GFP-LC3 transfection...
August 2018: Journal of Pharmacy and Pharmacology
Suzanne N Shapira, Hee-Woong Lim, Sona Rajakumari, Alexander P Sakers, Jeff Ishibashi, Matthew J Harms, Kyoung-Jae Won, Patrick Seale
The transcription factor early B-cell factor 2 (EBF2) is an essential mediator of brown adipocyte commitment and terminal differentiation. However, the mechanisms by which EBF2 regulates chromatin to activate brown fat-specific genes in adipocytes were unknown. ChIP-seq (chromatin immunoprecipitation [ChIP] followed by deep sequencing) analyses in brown adipose tissue showed that EBF2 binds and regulates the activity of lineage-specific enhancers. Mechanistically, EBF2 physically interacts with the chromatin remodeler BRG1 and the BAF chromatin remodeling complex in brown adipocytes...
April 1, 2017: Genes & Development
Y Zhang, J Y Wu, L H Weng, X X Li, L J Yu, Y Xu
Autophagy is a common physiological activity in cells. Studies show that dysregulation of autophagy is involved in the pathogenesis of Parkinson's disease (PD). As a commonly used anti-epileptic drug, valproic acid (VPA) has shown neuroprotective effects in PD. The aim of this study was to explore whether the autophagy induced by VPA involved in the neuroprotective effects in PD cell model. We found that VPA treatment counteracted MPP+ -caused autophagic flux impairment. Forthermore, VPA could alleviates apoptosis, reduce reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) loss caused by MPP+ ...
January 18, 2017: Neuroscience Letters
Wei Guo, Yu Wang, Zhu Wang, Yan-Ping Wang, Hong Zheng
Chemotherapy, radiotherapy, and endocrinotherapy are documented to induce autophagy among breast cancer cells, but the role of autophagy in this disease has been attributed as cytoprotective as well as tumor-suppressing. Thus we studied MDA-MB-231 and SK-BR-3 breast cancer cell lines treated with epirubicin (EPI) to assess autophagy and apoptosis. We found out that EPI induced apoptosis and autophagy in both cell lines. The lysosomal inhibitor bafilomycin A1 inhibited cellular autophagy and enhanced EPI-triggered apoptosis, perhaps due to inhibition of autolysosome formation, which then inhibited autophagic effects of engulfing and clearing damaged mitochondria...
November 2016: Cancer Science
Yuanna Ling, Guiming Chen, Yi Deng, Huixiong Tang, Long Ling, Xiaoming Zhou, Xudong Song, Pingzhen Yang, Yingfeng Liu, Zhiliang Li, Cong Zhao, Yufei Yang, Xianbao Wang, Masafumi Kitakaze, Yulin Liao, Aihua Chen
Polydatin (PD), a resveratrol (RES) glycoside, has a stronger antioxidative effect than RES. It is known that RES is an autophagic enhancer and exerts a cardioprotective effect against ischaemia/reperfusion (I/R) injury. However, the effect of PD post-treatment on myocardial I/R injury remains unclear. In the present study, we investigated the influences of PD post-treatment on myocardial I/R injury and autophagy. C57BL/6 mice underwent left coronary artery (LCA) occlusion and cultured neonatal rat cardiomyocytes (NRCs) subjected to hypoxia were treated with vehicle or PD during reperfusion or re-oxygenation...
September 1, 2016: Clinical Science (1979-)
Carina R Firkowski, Marcos R Bornschein, Luiz F Ribeiro, Marcio R Pie
The Brazilian Atlantic Forest (BAF) is recognized as one of the world's biodiversity hotspots, with even more species per unit of area than the Amazon, however the mechanisms that led to such astonishing diversity are yet to be fully understood. In this study, we investigate the diversification of two co-distributed frog genera associated with montane areas of southern BAF: Melanophryniscus (Bufonidae) and Brachycephalus (Brachycephalidae). Species delimitation methods using mitochondrial and nuclear loci supported the existence of a remarkable number of highly endemic species in each genus, most of which occupy only one or a few adjacent mountaintops...
July 2016: Molecular Phylogenetics and Evolution
Kai Jiang, Wei Wang, Xin Jin, Zhaoyang Wang, Zhiwei Ji, Guanmin Meng
Silibinin, derived from the milk thistle plant (Silybum marianum), has anticancer and chemopreventive properties. Silibinin has been reported to inhibit the growth of various types of cancer cells. However, the mechanisms by which silibinin exerts an anticancer effect are poorly defined. The present study aimed to investigate whether silibinin-induced cell death might be attributed to autophagy and the underlying mechanisms in human MCF7 breast cancer cells. Our results showed that silibinin-induced cell death was greatly abrogated by two specific autophagy inhibitors, 3-methyladenine (3-MA) and bafilomycin-A1 (Baf-A1)...
June 2015: Oncology Reports
Yue-Bao Ning, Zhi-Qiang Du
Apoptosis plays a crucial role for generation of lymphocyte repertoire, clonal contraction, and elimination of virus-infected cells. Since IL-3-dependent pro-B cell line Baf-3 resulted in rapid induction of apoptotic cell death upon IL-3 withdrawal, it would by very valuable for analysis of apoptosis induction by growth factor deprivation. First, we confirmed that Baf-3 cells underwent loss of mitochondrial membrane potential (ΔΨm) and apoptosis in a time-dependent manner when they were cultured in the RPMI-1640 medium without IL-3...
May 2015: Cell Biology International
Sara Sileno, Valentina D'Oria, Riccardo Stucchi, Massimo Alessio, Stefania Petrini, Valentina Bonetto, Pierre Maechler, Federico Bertuzzi, Valeria Grasso, Katia Paolella, Fabrizio Barbetti, Ornella Massa
UNLABELLED: Transglutaminase 2 (TG2) is a multifunctional protein with Ca(2+)-dependent transamidating and G protein activity. Previously we reported that the role of TG2 in insulin secretion may involve cytoplasmic actin remodeling and a regulative action on other proteins during granule movement. The aim of this study was to gain a better insight into the role of TG2 transamidating activity in mitochondria and in the nucleus of INS-1E rat insulinoma cell line (INS-1E) during insulin secretion...
January 16, 2014: Journal of Proteomics
W Y Wani, A Sunkaria, D R Sharma, R J L Kandimalla, A Kaushal, E Gerace, A Chiarugi, K D Gill
Numerous epidemiological studies have shown an association between pesticide exposure and the increased risk of developing Parkinson's disease. Previously we have reported that Dichlorvos exposure can induce oxidative stress, resulting in over-expression of pro-apoptotic genes and finally caspase-dependent nigrostriatal dopaminergic neuronal cell death in rat brain. Here, we examined the effect of caspase inhibition on PC12 cell death induced by Dichlorvos (30 μM). Reactive oxygen species (ROS) generation followed by protein carbonylation, lipid peroxidation, decreased antioxidant defenses (decreased Mn-superoxide dismutase (MnSOD) activity and decreased glutathione levels) and subsequent caspase activation mediated the apoptosis...
January 31, 2014: Neuroscience
James K Morelli, Paul J Ciaccio
Dog and rat hepatocytes were treated with phospholipogenics to identify the more sensitive species and to determine whether lysosomal or mitochondrial changes were the primary cause of cytotoxicity. Endpoints included cell death, lysosome membrane integrity, mitochondrial membrane polarization, and fluorescent phospholipid (NBD-PE). Dog cells exhibited lower survival IC50 values than did rat cells with all phospholipogenic treatments and exhibited a lower capacity to accumulate NBD-PE in 4 of 5 phospholipogenic test conditions...
2013: Journal of Toxicology
Alexander V Zhdanov, Ruslan I Dmitriev, Dmitri B Papkovsky
Mitochondrial uncoupling is implicated in many patho(physiological) states. Using confocal live cell imaging and an optical O2 sensing technique, we show that moderate uncoupling of the mitochondria with plecomacrolide Baf (bafilomycin A1) causes partial depolarization of the mitochondria and deep sustained deoxygenation of human colon cancer HCT116 cells subjected to 6% atmospheric O2. A decrease in iO2 (intracellular O2) to 0-10 μM, induced by Baf, is sufficient for stabilization of HIFs (hypoxia inducible factors) HIF-1α and HIF-2α, coupled with an increased expression of target genes including GLUT1 (glucose transporter 1), HIF PHD2 (prolyl hydroxylase domain 2) and CAIX (carbonic anhydrase IX)...
December 2012: Bioscience Reports
Lisa M Greene, Niamh M O'Boyle, Derek P Nolan, Mary J Meegan, Daniela M Zisterer
Recent clinical data demonstrated that the vascular targeting agent Combretastatin-A4 phosphate (CA-4P) prolonged survival of patients with advanced anaplastic thyroid cancer without any adverse side effects. However, as a single agent CA-4 failed to reduce tumour growth in the murine CT-26 adenocarcinoma colon cancer model. Furthermore, the molecular mechanism of the innate resistance of HT-29 human adenocarcinoma cells to CA-4 is largely unknown. In this report, we demonstrate for the first time that prolonged exposure to CA-4 and an azetidinone cis-restricted analogue, CA-432 (chemical name; 4-(3-Hydroxy-4-methoxyphenyl)-3-phenyl-1-(3,4,5-trimethoxyphenyl)-azetidin-2-one) induced autophagy in adenocarcinoma-derived CT-26, Caco-2 and HT-29 cells but not in fibrosarcoma-derived HT-1080 cells...
September 1, 2012: Biochemical Pharmacology
Alexander V Zhdanov, Ruslan I Dmitriev, Dmitri B Papkovsky
Bafilomycin A1 (Baf) induces an elevation of cytosolic Ca(2+) and acidification in neuronal cells via inhibition of the V-ATPase. Also, Baf uncouples mitochondria in differentiated PC12 ((d)PC12), (d)SH-SY5Y cells and cerebellar granule neurons, and markedly elevates their respiration. This respiratory response in (d)PC12 is accompanied by morphological changes in the mitochondria and decreases the mitochondrial pH, Ca(2+) and ΔΨm. The response to Baf is regulated by cytosolic Ca(2+) fluxes from the endoplasmic reticulum...
March 2011: Cellular and Molecular Life Sciences: CMLS
Tuliana O Brunes, Fernando Sequeira, Célio F B Haddad, João Alexandrino
The Neotropical Phyllomedusa burmeisteri treefrog group includes four diploid (P. bahiana, P. burmeisteri, P. distincta and P. iheringii) and one tetraploid (P. tetraploidea) forms. Here we use mitochondrial and nuclear sequence variation from across its range to verify if recognized morphospecies correspond to phylogenetic clades, examine the origin of the polyploid P. tetraploidea, and compare range wide patterns of diversification to those of other BAF organisms. We compared single gene trees with one Bayesian multi-gene tree, and one Bayesian species tree inferred under a coalescent framework...
December 2010: Molecular Phylogenetics and Evolution
Saeid Ghavami, Mehdi Eshragi, Sudharsana R Ande, Walter J Chazin, Thomas Klonisch, Andrew J Halayko, Karol D McNeill, Mohammad Hashemi, Claus Kerkhoff, Marek Los
The complex formed by two members of the S100 calcium-binding protein family, S100A8/A9, exerts apoptosis-inducing activity in various cells of different origins. Here, we present evidence that the underlying molecular mechanisms involve both programmed cell death I (PCD I, apoptosis) and PCD II (autophagy)-like death. Treatment of cells with S100A8/A9 caused the increase of Beclin-1 expression as well as Atg12-Atg5 formation. S100A8/A9-induced cell death was partially inhibited by the specific PI3-kinase class III inhibitor, 3-methyladenine (3-MA), and by the vacuole H(+)-ATPase inhibitor, bafilomycin-A1 (Baf-A1)...
March 2010: Cell Research
T A Mejía-García, R Paes-de-Carvalho
Nitric oxide (NO) is an important signaling molecule in the CNS, regulating neuronal survival, proliferation and differentiation. Here, we explored the mechanism by which NO, produced from the NO donor S-nitroso-acetyl-d-l-penicillamine (SNAP), exerts its neuroprotective effect in purified cultures of chick retinal neurons. Cultures prepared from 8-day-old chick embryo retinas and incubated for 24 h (1 day in culture, C1) were treated or not with SNAP, incubated for a further 72 h (up to 4 days in culture, C4), fixed, and the number of cells estimated, or processed for cell death estimation, by measuring the reduction of the metabolic dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)...
January 2007: Journal of Neurochemistry
Robert S B Clark, Paula D Nathaniel, Xiaopeng Zhang, C Edward Dixon, Sean M Alber, Simon C Watkins, John A Melick, Patrick M Kochanek, Steven H Graham
The pathobiology of traumatic brain injury (TBI) includes activation of multiple caspases followed by cell death with a spectrum of apoptotic phenotypes. There are initiator (e.g. caspase-2, -8, and -9) and effector (e.g. caspase-3 and -7) caspases. Recently, caspase-2 and -8 have been shown to regulate cell death via provoking cytochrome c release from the mitochondria upstream of caspase-9. Here, we show that an intracerebral injection of the pan-caspase inhibitor boc-Aspartyl(OMe)-fluoromethylketone (BAF; 1 micromol) 1 min after TBI in rats reduces caspase-3-like activity, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and tissue damage, and cytochrome c release in ipsilateral cortex at 24 h versus vehicle...
February 2007: Journal of Cerebral Blood Flow and Metabolism
Vanessa Desplat, Francis Belloc, Valérie Lagarde, Catherine Boyer, Junia V Melo, Josy Reiffers, Vincent Praloran, François-Xavier Mahon
BACKGROUND: Imatinib mesylate, a BCR-ABL tyrosine kinase inhibitor, induces apoptosis in chronic myeloid leukemia cells. Resistance to imatinib is currently the most important concern of this treatment. One of the main mechanisms of this resistance is overexpression of BCR-ABL. METHODS: In the current study, the authors investigated the correlation between BCR-ABL overexpression and apoptosis in BaF/BCR-ABL and LAMA84 cell lines resistant to imatinib suddenly deprived of the inhibitor, and compared with their sensitive counterpart...
January 1, 2005: Cancer
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