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Mitochondrial permeability transition pore

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https://www.readbyqxmd.com/read/28324237/cyclosporine-a-induces-endoplasmic-reticulum-stress-and-influences-pro-apoptotic-factors-in-human-gingival-fibroblasts
#1
Suresh Ranga Rao, Shiyamali Sundararajan, Rajasekaran Subbarayan, Dinesh Murugan Girija
Cyclosporine-A (CsA) induces gingival overgrowth. Cyclosporine's anti-apoptotic activity in human gingival fibroblast is due to desensitization of mitochondrial permeability transition pore (MPTP) and augmentation of anti-apoptotic, Bcl2. Alternative mechanisms of apoptosis exist involving enzymes like calcium-dependent Calpain and signaling events related to apoptosis, like Glycogen synthase kinase 3β (GSK3β) and protein kinase A (PKA). Cyclosporine-A in renal tubular cells induces endoplasmic reticulum stress (ER stress) which has not been explored in gingival overgrowth...
March 21, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28317877/transcription-factor-nf-kappa-b-represses-ant1-transcription-and-leads-to-mitochondrial-dysfunctions
#2
Chen Zhang, Hui Jiang, Pin Wang, Heng Liu, Xiulian Sun
Mitochondria are intracellular organelles involved in cell survival and death, and dysfunctions of mitochondria are related to neurodegenerative diseases. As the most abundant protein in the mitochondrial inner membrane, adenine nucleotide translocator 1 (ANT1) plays a critical role in mitochondrial function, including the exchange of adenosine triphosphate/adenosine diphosphate (ATP/ADP) in mitochondria, basal proton leak and mitochondrial permeability transition pore (mPTP). Here, we show that ANT1 transcription is regulated by transcription factor NF-kappa B (NF-κB)...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28292971/selective-replacement-of-mitochondrial-dna-increases-cardioprotective-effect-of-chronic-continuous-hypoxia-in-spontaneously-hypertensive-rats
#3
Jan Neckar, Anna Svatonova, Romana Weissova, Zdenek Drahota, Pavlina Zajickova, Iveta Brabcova, David Kolar, Petra Alanova, Jana Vasinova, Jan Silhavy, Marketa Hlavackova, Katerina Tauchmannova, Marie Milerova, Bohuslav Ostadal, Ludek Cervenka, Jitka Zurmanova, Martin Kalous, Olga Novakova, Jiri Novotny, Michal Pravenec, Frantisek Kolar
Mitochondria play an essential role in improved cardiac ischemic tolerance conferred by adaptation to chronic hypoxia. In the present study, we analyzed effects of continuous normobaric hypoxia (CNH) on mitochondrial functions, including the sensitivity of mitochondrial permeability transition pore (MPTP) to opening, and infarct size in hearts of spontaneously hypertensive rats (SHR) and in conplastic SHR-mtBN strain characterized by the selective replacement of the mitochondrial genome of SHR with that of more ischemia-resistant Brown Norway (BN) strain...
March 14, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28289229/persistence-of-the-mitochondrial-permeability-transition-in-the-absence-of-subunit-c-of-human-atp-synthase
#4
Jiuya He, Holly C Ford, Joe Carroll, Shujing Ding, Ian M Fearnley, John E Walker
The permeability transition in human mitochondria refers to the opening of a nonspecific channel, known as the permeability transition pore (PTP), in the inner membrane. Opening can be triggered by calcium ions, leading to swelling of the organelle, disruption of the inner membrane, and ATP synthesis, followed by cell death. Recent proposals suggest that the pore is associated with the ATP synthase complex and specifically with the ring of c-subunits that constitute the membrane domain of the enzyme's rotor...
March 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28288978/mff-dependent-mitochondrial-fission-contributes-to-the-pathogenesis-of-cardiac-microvasculature-ischemia-reperfusion-injury-via-induction-of-mros-mediated-cardiolipin-oxidation-and-hk2-vdac1-disassociation-involved-mptp-opening
#5
Hao Zhou, Shunying Hu, Qinhua Jin, Chen Shi, Ying Zhang, Pingjun Zhu, Qiang Ma, Feng Tian, Yundai Chen
BACKGROUND: The cardiac microvascular system ischemia/reperfusion injury following percutaneous coronary intervention is a clinical thorny problem. This study explores the mechanisms by which ischemia/reperfusion injury induces cardiac microcirculation collapse. METHODS AND RESULTS: In wild-type mice, mitochondrial fission factor (Mff) expression increased in response to acute microvascular ischemia/reperfusion injury. Compared with wild-type mice, homozygous Mff-deficient (Mff(gt)) mice exhibited a smaller infarcted area, restored cardiac function, improved blood flow, and reduced microcirculation perfusion defects...
March 13, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28284974/mevalonolactone-disrupts-mitochondrial-functions-and-induces-permeability-transition-pore-opening-in-rat-brain-mitochondria-implications-for-the-pathogenesis-of-mevalonic-aciduria
#6
Cristiane Cecatto, Alexandre Umpierrez Amaral, Janaína Camacho da Silva, Alessandro Wajner, Kálita Dos Santos Godoy, Rafael Teixeira Ribeiro, Aline de Mello Gonçalves, Carmen Regla Vargas, Moacir Wajner
Mevalonic aciduria (MVA) is caused by severe deficiency of mevalonic kinase activity leading to tissue accumulation and high urinary excretion of mevalonic acid (MA) and mevalonolactone (ML). Patients usually present severe neurologic symptoms whose pathophysiology is poorly known. Here, we tested the hypothesis that the major accumulating metabolites are toxic by investigating the in vitro effects of MA and ML on important mitochondrial functions in rat brain and liver mitochondria. ML, but not MA, markedly decreased mitochondrial membrane potential (ΔΨm), NAD(P)H content and the capacity to retain Ca(2+) in the brain, besides inducing mitochondrial swelling...
March 8, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28281894/in-vitro-cytotoxicity-assessment-of-roundup-glyphosate-in-l-02-hepatocytes
#7
Lei Luo, Fei Wang, Yiyuan Zhang, Ming Zeng, Caigao Zhong, Fang Xiao
The goal of the present study was to elucidate the in vitro cytotoxicity of Roundup and to reveal the possible related mechanisms in L-02 hepatocytes. By detecting reactive oxygen species (ROS) production, glutathione (GSH)/superoxide dismutase (SOD) levels, mitochondrial permeability transition pore (PTP) open rate, apoptosis-inducing factor (AIF) release, intracellular Ca(2+) concentration, and alanine aminotransferease (ALT)/aspartate aminotransferase (AST) leakage, we determined that Roundup induced anti-oxidant system inhibition, mitochondria damage, DNA damage, membrane integrity and permeability changes, and apoptosis in L-02 hepatocytes...
March 10, 2017: Journal of Environmental Science and Health. Part. B, Pesticides, Food Contaminants, and Agricultural Wastes
https://www.readbyqxmd.com/read/28279675/synchronism-in-mitochondrial-ros-flashes-membrane-depolarization-and-calcium-sparks-in-human-carcinoma-cells
#8
Andrey V Kuznetsov, Sabzali Javadov, Valdur Saks, Raimund Margreiter, Michael Grimm
Mitochondria are major producers of reactive oxygen species (ROS) in many cells including cancer cells. However, complex interrelationships between mitochondrial ROS (mitoROS), mitochondrial membrane potential (ΔΨm) and Ca(2+) are not completely understood. Using human carcinoma cells, we further highlight biphasic ROS dynamics: - gradual mitoROS increase followed by mitoROS flash. Also, we demonstrate heterogeneity in rates of mitoROS generation and flash initiation time. Comparing mitochondrial and near-extra-mitochondrial signals, we show that mechanisms of mitoROS flashes in single mitochondria, linked to mitochondrial permeability transition pore opening (ΔΨm collapse) and calcium sparks, may involve flash triggering by certain levels of external ROS released from the same mitochondria...
March 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28273124/blockade-of-cyclophilin-d-rescues-dexamethasone-induced-oxidative-stress-in-gingival-tissue
#9
Yuting He, Ling Zhang, Zhuoli Zhu, Anqi Xiao, Haiyang Yu, Xueqi Gan
Glucocorticoids (GCs) are frequently used for the suppression of inflammation in chronic inflammatory diseases. Excessive GCs usage is greatly associated with several side effects, including gingival ulceration, the downward migration of the epithelium, attachment loss and disruption of transeptal fibers. The mechanisms underlying GCs-induced impairments in gingival tissue remains poorly understood. Mitochondrial dysfunction is associated with various oral diseases, such as chronic periodontitis, age-related alveolar bone loss and hydrogen peroxide-induced cell injury in gingival...
2017: PloS One
https://www.readbyqxmd.com/read/28266127/mitochondrial-pkc-%C3%AE%C2%B5-deficiency-promotes-i-r-mediated-myocardial-injury-via-gsk3%C3%AE-dependent-mitochondrial-permeability-transition-pore-opening
#10
Shijun Wang, Feng Zhang, Gang Zhao, Yong Cheng, Ting Wu, Bing Wu, You-En Zhang
Mitochondrial fission is critically involved in cardiomyocyte apoptosis, which has been considered as one of the leading causes of ischaemia/reperfusion (I/R)-induced myocardial injury. In our previous works, we demonstrate that aldehyde dehydrogenase-2 (ALDH2) deficiency aggravates cardiomyocyte apoptosis and cardiac dysfunction. The aim of this study was to elucidate whether ALDH2 deficiency promotes mitochondrial injury and cardiomyocyte death in response to I/R stress and the underlying mechanism. I/R injury was induced by aortic cross-clamping for 45 min...
March 7, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28261564/legionella-pneumophila-strain-130b-evades-macrophage-cell-death-independent-of-the-effector-sidf-in-the-absence-of-flagellin
#11
Mary Speir, Adam Vogrin, Azadeh Seidi, Gilu Abraham, Stéphane Hunot, Qingqing Han, Gerald W Dorn, Seth L Masters, Richard A Flavell, James E Vince, Thomas Naderer
The human pathogen Legionella pneumophila must evade host cell death signaling to enable replication in lung macrophages and to cause disease. After bacterial growth, however, L. pneumophila is thought to induce apoptosis during egress from macrophages. The bacterial effector protein, SidF, has been shown to control host cell survival and death by inhibiting pro-apoptotic BNIP3 and BCL-RAMBO signaling. Using live-cell imaging to follow the L. pneumophila-macrophage interaction, we now demonstrate that L. pneumophila evades host cell apoptosis independent of SidF...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28251264/calcium-induced-mitochondrial-permeability-transitions-parameters-of-ca-2-ion-interactions-with-mitochondria-and-effects-of-oxidative-agents
#12
Nina G Golovach, Vitali T Cheshchevik, Elena A Lapshina, Tatsiana V Ilyich, Ilya B Zavodnik
We evaluated the parameters of Ca(2+)-induced mitochondrial permeability transition (MPT) pore formations, Ca(2+) binding constants, stoichiometry, energy of activation, and the effect of oxidative agents, tert-butyl hydroperoxide (tBHP), and hypochlorous acid (HOCl), on Ca(2+) -mediated process in rat liver mitochondria. From the Hill plot of the dependence of MPT rate on Ca(2+) concentration, we determined the order of interaction of Ca(2+) ions with the mitochondrial sites, n = 3, and the apparent Kd = 60 ± 12 µM...
March 1, 2017: Journal of Membrane Biology
https://www.readbyqxmd.com/read/28247434/melatonin-protects-against-lipid-induced-mitochondrial-dysfunction-in-hepatocytes-and-inhibits-stellate-cell-activation-during-hepatic-fibrosis-in-mice
#13
Nabanita Das, Ashok Mandala, Shamreen Naaz, Suresh Giri, Mukul Jain, Debasish Bandyopadhyay, Russel J Reiter, Sib Sankar Roy
Lipid generates reactive oxygen species (ROS) in consequence to mitochondrial fission followed by inflammation in propagating hepatic fibrosis. The interaction of SIRT1/Mitofusin2 is critical for maintaining mitochondrial integrity and functioning, which is disrupted upon excess lipid infiltration during the progression of steatohepatitis. The complex interplay between hepatic stellate cells and steatotic hepatocytes is critically regulated by extracellular factors including increased circulating free fatty acids during fibrogenesis...
March 1, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28245918/mitochondrial-calcium-sparkles-light-up-astrocytes
#14
Brian A MacVicar, Rebecca W Y Ko
Discrete calcium signals in the fine processes of astrocytes are a recent discovery and a new mystery. In a recent issue of Neuron, Agarwal et al. (2017) report that calcium efflux from mitochondria during brief openings of the mitochondrial permeability transition pore (mPTP) contribute to calcium microdomains.
February 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28236057/regulation-of-sirtuin-3-mediated-deacetylation-of-cyclophilin-d-attenuated-cognitive-dysfunction-induced-by-sepsis-associated-encephalopathy-in-mice
#15
Fan Sun, Yanna Si, Hongguang Bao, Yajie Xu, XiaoXiao Pan, Lingqing Zeng, Ling Jing
The present study aimed to investigate cognitive dysfunction in the hippocampus induced by sepsis-associated encephalopathy (SAE) via acetylation of cyclophilin D (CypD) and opening of mitochondrial permeability transition pore. It also explored whether activating sirtuin 3 (SIRT3) can mediate deacetylation of CypD and prevent the development of SAE. Male mice were randomly assigned to six groups: sham group, cecal ligation puncture group, CypD siRNA transfection (CypD-si) group, CypD control siRNA transfection (CypD-c) group, SIRT3 overexpression vector pcDNA3...
February 25, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28230856/ginsenoside-rg5-increases-cardiomyocyte-resistance-to-ischemic-injury-through-regulation-of-mitochondrial-hexokinase-ii-and-dynamin-related-protein-1
#16
Yi-Lin Yang, Jia Li, Kang Liu, Lei Zhang, Qun Liu, Baolin Liu, Lian-Wen Qi
Hexokinase-II (HK-II) and dynamin-related protein 1 (Drp1) regulate mitochondrial function differently. This study was designed to investigate the cardioprotective effect of ginsenoside Rg5 (Rg5) with emphasis on the regulation of mitochondrial HK-II and Drp1. Saturated acid palmitate (PA) stimulation increased lactate accumulation and induced cellular acidification by impairing the activity of pyruvate dehydrogenase (PDH) in cardiomyocytes, leading to HK-II dissociation from mitochondria. Rg5 improved PDH activity and prevented cellular acidification by combating fatty-acid oxidation, contributing to protecting mitochondrial HK-II...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230282/ablation-of-cyclophilin-d-results-in-an-activation-of-fak-akt-and-erk-pathways-in-the-mouse-heart
#17
Jelena Klawitter, Tamas Seres, Alexander Pennington, Jonathan-Thomas Beatty, Jost Klawitter, Uwe Christians
Cyclophilin D (CypD) is a mitochondrial chaperone that regulates the mitochondrial permeability transition pore. Metabolically, deletion of Ppif (the gene encoding CypD) in mice is associated with elevated levels of mitochondrial matrix Ca(2+) that leads to increased glucose as relative to fatty acid oxidation. Here, we characterized the adaptive mechanisms involved in the regulation of glucose metabolism including the regulation of Akt and ERK kinases that we evaluated by Western blot analysis of Ppif-/-in comparison to wild type (WT) mouse hearts...
February 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28224704/advanced-glycation-end-products-regulate-anabolic-and-catabolic-activities-via-nlrp3-inflammasome-activation-in-human-nucleus-pulposus-cells
#18
Yu Song, Yan Wang, Yukun Zhang, Wen Geng, Wei Liu, Yong Gao, Shuai Li, Kun Wang, Xinghuo Wu, Liang Kang, Cao Yang
Intervertebral disc degeneration is widely recognized as a cause of lower back pain, neurological dysfunction and other musculoskeletal disorders. The major inflammatory cytokine IL-1β is associated with intervertebral disc degeneration; however, the molecular mechanisms that drive IL-1β production in the intervertebral disc, especially in nucleus pulposus (NP) cells, are unknown. In some tissues, advanced glycation end products (AGEs), which accumulate in NP tissues and promote its degeneration, increase oxidative stress and IL-1β secretion, resulting in disorders, such as obesity, diabetes mellitus and ageing...
February 22, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28224174/spectroscopic-polarographic-and-microcalorimetric-studies-on-mitochondrial-dysfunction-induced-by-ethanol
#19
Long Ma, Jia-Xin Dong, Can Wu, Xue-Yi Li, Jing Chen, Hong Zhang, Yi Liu
Liver mitochondria are involved in several important life processes; mitochondrial dysfunction and disorders are implicated in several human diseases. Alcohol permeates all tissues of the body and exerts some intrinsic hepatotoxicity. In this work, our results demonstrated that ethanol caused a series of mitochondria permeability transition pore (MPTP) opening factors such as mitochondrial swelling, increased permeability of H(+) and K(+), collapsed membrane potential, and increased membrane fluidity. Furthermore, mitochondrial ultrastructure alternation observed clearly by transmission electron microscopy and the release of Cytochrome c could explain the MPTP opening from another aspect...
February 21, 2017: Journal of Membrane Biology
https://www.readbyqxmd.com/read/28197936/salvianolic-acid-a-protects-neonatal-cardiomyocytes-against-hypoxia-reoxygenation-induced-injury-by-preserving-mitochondrial-function-and-activating-akt-gsk-3%C3%AE-signals
#20
Xue-Li Li, Ji-Ping Fan, Jian-Xun Liu, Li-Na Liang
OBJECTIVE: To investigate the effects of salvianolic acid A (SAA) on cardiomyocyte apoptosis and mitochondrial dysfunction in response to hypoxia/reoxygenation (H/R) injury and to determine whether the Akt signaling pathway might play a role. METHODS: An in vitro model of H/R injury was used to study outcomes on primary cultured neonatal rat cardiomyocytes. The cardiomyocytes were treated with 12.5, 25, 50 μg/mL SAA at the beginning of hypoxia and reoxygenation, respectively...
February 15, 2017: Chinese Journal of Integrative Medicine
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