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Mitochondrial permeability transition pore

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https://www.readbyqxmd.com/read/29332286/analysis-of-mitochondrial-markers-of-programmed-cell-death
#1
Dong Xiao, Huyi He, Wenjing Huang, Thet Lwin Oo, Aiqin Wang, Long-Fei He
Mitochondria play a crucial role in programmed cell death (PCD) in plants. In most cases of mitochondria-dependent PCD, cytochrome c (Cyt c) released from mitochondria due to the opening of mitochondrial permeability transition pore (MPTP) and the activation of caspase-like proteases. Here we describe the analytic methods of mitochondrial markers of PCD including mitochondria isolation, mitochondrial membrane permeability, mitochondrial inner membrane potential, Cytc release, ATP, and mitochondrial reactive oxygen species (ROS)...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29331741/extracellular-acidification-induces-ros-and-mptp-mediated-death-in-hek293-cells
#2
José Teixeira, Farhan Basit, Herman G Swarts, Marleen Forkink, Paulo J Oliveira, Peter H G M Willems, Werner J H Koopman
The extracellular pH (pHe) is a key determinant of the cellular (micro)environment and needs to be maintained within strict boundaries to allow normal cell function. Here we used HEK293 cells to study the effects of pHe acidification (24h), induced by mitochondrial inhibitors (rotenone, antimycin A) and/or extracellular HCl addition. Lowering pHe from 7.2 to 5.8 reduced cell viability by 70% and was paralleled by a decrease in cytosolic pH (pHc), hyperpolarization of the mitochondrial membrane potential (Δψ), increased levels of hydroethidine-oxidizing ROS and stimulation of protein carbonylation...
December 30, 2017: Redox Biology
https://www.readbyqxmd.com/read/29323705/the-protective-effects-of-distal-ischemic-treatment-on-apoptosis-and-mitochondrial-permeability-in-the-hippocampus-after-cardiopulmonary-resuscitation
#3
Xiang Zhou, Liu Yong, Yang Huang, ShuiBo Zhu, XiaoYang Song, BiXi Li, Jian Zhu, HaiBo Wang
BACKGROUND: Apoptosis and mitochondrial dysfunction are the main cause of neurological injury after cardiopulmonary resuscitation (CPR). However, the effects of distal ischemic treatments on ischemia-induced apoptosis are rarely studied, and the mechanism by which mitochondrial dysfunction contributes to CPR still unclear. METHODS: A rat model of distal ischemia was established by clipping the right femoral artery. Rats were divided into blank, model, pre-distal ischemic treatment, per-treatment, and post-treatment groups...
January 11, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29317705/pneumolysin-induced-mitochondrial-dysfunction-leads-to-release-of-mitochondrial-dna
#4
Andreas Nerlich, Maren Mieth, Eleftheria Letsiou, Diana Fatykhova, Katja Zscheppang, Aki Imai-Matsushima, Thomas F Meyer, Lisa Paasch, Timothy J Mitchell, Mario Tönnies, Torsten T Bauer, Paul Schneider, Jens Neudecker, Jens C Rückert, Stephan Eggeling, Maria Schimek, Martin Witzenrath, Norbert Suttorp, Stefan Hippenstiel, Andreas C Hocke
Streptococcus pneumoniae (S.pn.) is the most common bacterial pathogen causing community acquired pneumonia. The pore-forming toxin pneumolysin (PLY) is the major virulence factor of S.pn. and supposed to affect alveolar epithelial cells thereby activating the immune system by liberation of danger-associated molecular patterns (DAMP). To test this hypothesis, we established a novel live-cell imaging based assay to analyse mitochondrial function and associated release of mitochondrial DNA (mtDNA) as DAMP in real-time...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29313986/protein-kinase-d-activation-induces-mitochondrial-fragmentation-and-dysfunction-in-cardiomyocytes
#5
Bong Sook Jhun, Jin O-Uchi, Stephanie M Adaniya, Tomas J Mancini, Jessica L Cao, Michelle E King, Amy K Landi, Hanley Ma, Milla Shin, Donqin Yang, Xiaole Xu, Yisang Yoon, Gaurav Choudhary, Richard T Clements, Ulrike Mende, Shey-Shing Sheu
Regulation of mitochondrial morphology is crucial for the maintenance of physiological functions in many cell types including cardiomyocytes. Small and fragmented mitochondria are frequently observed in pathological condition, but it is still unclear which cardiac signalling pathway is responsible for regulating the abnormal mitochondrial morphology in cardiomyocytes. Here we demonstrate that a downstream kinase of Gq -protein coupled receptor (Gq PCR) signalling, protein kinase D (PKD), mediates pathophysiological modifications in mitochondrial morphology and function, which consequently contribute to the activation of apoptotic signalling...
January 5, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29305524/-hete-ing-up-mitochondria-in-human-heart-failure
#6
Matthew J Wolf
A decade of research has established the phospholipase iPLA2γ as being involved in cardiomyocyte dysfunction and necrosis leading to heart failure, but the mechanisms by which iPLA2γ acts and its interaction with the mitochondrial permeability transition pore (mPTP) that is critical for cardiac homeostasis are unclear. New investigations by Moon et al. demonstrate that mitochondria in failing hearts undergo dynamic shifts in PLA2 isoform expression, leading to a redistribution of eicosanoid composition that contributes to pathologic mPTP opening...
January 5, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29302888/overexpression-of-aryl-hydrocarbon-receptor-ahr-signalling-pathway-in-human-meningioma
#7
Noble Kumar Talari, Manas K Panigrahi, Sailaja Madigubba, Prakash Babu Phanithi
Aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor and involved in tumorigenesis of many cancers. However there are no reports on AHR in human meningioma. Therefore we examined the status of the AHR and its signalling molecules in human meningioma by using tumor biopsy samples and autopsy control meninges. We report the up regulation of AHR pathway genes like aryl hydrocarbon receptor nuclear translocator (ARNT), aldehyde dehydrogenase1family memberA3 (ALDH1A3), cytochrome P450, family1, subfamily A polypeptide1 (CYP1A1) and TCCD induced poly ADP ribose polymerase (TIPARP) gene expression in human meningioma...
January 4, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29299124/fty-720-induces-apoptosis-in-neuroblastoma-via-multiple-signaling-pathways
#8
Ingo Lange, Italo Espinoza-Fuenzalida, Mourad Wagdy Ali, Laura Espana Serrano, Dana-Lynn T Koomoa
Neuroblastoma (NB) is the most common extra-cranial pediatric solid tumor. High-risk NB is difficult to treat due to the lack of response to current therapies and aggressive disease progression. Despite novel drugs, alternative treatments and multi-modal treatments, finding an effective treatment strategy for these patients continues to be a major challenge. The current study focuses on examining the effects of FTY-720 or fingolimod, a drug that is FDA-approved for refractory multiple sclerosis, in NB. The results showed that FTY-720 regulates multiple pathways that result in various effects on calcium signaling, ion channel activation and cell survival/death pathways...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29295576/intracellular-renin-inhibits-mitochondrial-permeability-transition-pore-via-activated-mitochondrial-extracellular-signal-regulated-kinase-erk-1-2-during-ischemia-in-diabetic-hearts
#9
Terumori Satoh, Masao Saotome, Hideki Katoh, Daishi Nonaka, Prottoy Hasan, Hideharu Hayashi, Yuichiro Maekawa
Although beneficial effects of non-secreting intracellular renin (ns-renin) against ischemia have been reported, the precise mechanism remains unclear. In this study, we investigated the roles of ns-renin and mitochondrial extracellular signal-related kinase (ERK) 1/2 on mitochondrial permeability transition pore (mPTP) opening during ischemia in diabetes mellitus (DM) hearts. When isolated hearts from Wistar rats (non-DM hearts) and Goto-Kakizaki rats (DM hearts) were subjected to ischemia for 70 min by left anterior descending coronary artery ligation, DM hearts exhibited higher left ventricular (LV) developed pressure and lower LV end-diastolic pressure than non-DM hearts, suggesting ischemic resistance...
December 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29288949/synthesis-and-evaluation-of-2-3-arylureido-pyridines-and-2-3-arylureido-pyrazines-as-potential-modulators-of-a%C3%AE-induced-mitochondrial-dysfunction-in-alzheimer-s-disease
#10
Ahmed Elkamhawy, Jung-Eun Park, Ahmed H E Hassan, Ae Nim Pae, Jiyoun Lee, Beoung-Geon Park, Eun Joo Roh
A series of 2-(3-arylureido)pyridines and 2-(3-benzylureido)pyridines were synthesized and evaluated as potential modulators for amyloid beta (Aβ)-induced mitochondrial dysfunction in Alzheimer's disease (AD). The blocking activities of forty one small molecules against Aβ-induced mitochondrial permeability transition pore (mPTP) opening were evaluated by JC-1 assay which measures the change of mitochondrial membrane potential (ΔΨm). The inhibitory activity of twenty five compounds against Aβ-induced mPTP opening was superior to that of the standard cyclosporin A (CsA)...
December 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29288688/neuroprotective-activity-of-macamides-on-manganese-induced-mitochondrial-disruption-in-u-87-mg-glioblastoma-cells
#11
Kuljeet S Gugnani, Nguyen Vu, Alejandro N Rondón-Ortiz, Mark Böhlke, Timothy J Maher, Alejandro J Pino-Figueroa
Macamides are a distinct class of secondary metabolites, benzylamides of long chain fatty acids, which were isolated from the Peruvian plant Lepidium meyenii (Maca). As structural analogues of the endocannabinoid anandamide (AEA), they have demonstrated neuroprotective effects in vitro and in vivo. The purpose of this study was to demonstrate the neuroprotective activity of the macamides: N-(3-methoxybenzyl)oleamide (MAC 18:1), N-(3-methoxybenzyl)linoleamide (MAC 18:2) and N-(3-methoxybenzyl)linolenamide (MAC 18:3) in a neurotoxic environment caused by exposure of U-87 MG glioblastoma cells to manganese chloride (MnCl2)...
December 27, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29286061/cardioprotection-by-exenatide-a-novel-mechanism-via-improving-mitochondrial-function-involving-the-glp-1-receptor-camp-pka-pathway
#12
Guanglei Chang, Jian Liu, Shu Qin, Youqin Jiang, Peng Zhang, Hui Yu, Kai Lu, Nan Zhang, Li Cao, Ying Wang, Yong Li, Dongying Zhang
Accumulating evidence suggests that glucagon-like peptide-1 (GLP-1) and its analogues exert cardioprotective effects via modulating cardiomyocyte metabolism. Mitochondria play a pivotal role in the regulation of cell metabolism. It was hypothesized that treatment with exenatide, a GLP-1 analogue, may exert cardioprotective effects by improving mitochondrial function in an in vitro model of hypoxia/reoxygenation (H/R). H9c2 cells were employed to establish an in vitro model of H/R. Exenatide was added to the cells for 30 min prior to exposure to hypoxia...
December 12, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29285102/protective-effects-of-carnosic-acid-against-mitochondria-mediated-injury-in-h9c2-cardiomyocytes-induced-by-hypoxia-reoxygenation
#13
Ping Liu, Jing Dong
Myocardial ischemia and reperfusion occurs in myocardial infarction. Timely reperfusion will exacerbate the injury through the mitochondria-mediated apoptosis in cardiomyocytes due to the accumulation of excessive reactive oxygen species (ROS). In order to identify novel therapeutic approaches, the cardioprotective effects of carnosic acid and the underlying mechanisms were investigated in the present study in H9c2 cardiomyocytes injured by hypoxia/reoxygenation in vitro. The viability of H9c2 cardiomyocytes was detected by MTT assay and further confirmed by the detection of intracellular lactate dehydrogenase (LDH) release...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29282302/acid-sphingomyelinase-promotes-mitochondrial-dysfunction-due-to-glutamate-induced-regulated-necrosis
#14
Sergei A Novgorodov, Joshua R Voltin, Monika A Gooz, Li Li, John J Lemasters, Tatyana I Gudz
Inhibiting the glutamate/cystine antiporter system xc-, a key antioxidant defense machinery in the CNS, could trigger a novel form of regulated necrotic cell death, ferroptosis. The underlying mechanisms of system xc--dependent cell demise were elucidated using primary oligodendrocytes (OLs) treated with glutamate to block system xc- function. Pharmacological analysis revealed ferroptosis as a major contributing factor to glutamate-initiated OL death. Sphingolipid profile showed elevations of ceramide species and sphingosine that were preventable by inhibiting of an acid sphingomyelinase (ASM) activity...
December 27, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/29282063/effect-of-atp-and-bax-on-the-apoptosis-of-eimeria-tenella-host-cells
#15
Zhiyong Xu, Mingxue Zheng, Li Zhang, Xuesong Zhang, Yan Zhang, Xiaozhen Cui, Xin Gong, Rou Xi, Rui Bai
BACKGROUND: Eimeria tenella (E. tenella) is a species of Eimeria that causes haemorrhagic caecal coccidiosis, resulting in major economic losses in the global poultry industry. After E. tenella infection, the amount of ATP and Bax in host cells showed highly significant changes. Therefore, it is necessary to investigate the effects of ATP and Bax on the apoptosis of E. tenella host cells. RESULTS: The ATP-treated group and the V5-treated group had higher E. tenella infection rates than the untreated group at 24, 48, 72, 96, and 120 h after infection with E...
December 28, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/29250127/cardioprotective-effect-of-danshensu-against-ischemic-reperfusion-injury-via-c-subunit-of-atp-synthase-inhibition
#16
Qing Gao, JingYi Zhao, Zixuan Fan, Jiadi Bao, Dawei Sun, Huhu Li, Chun Sun, Xijuan Jiang
Mitochondrial permeability transition pore (MPTP) opening is the main culprit of ischemic/reperfusion (IR) injury. It is reported that c-subunit of ATP synthase is the core component of MPTP. Danshensu (DSS), a monomer isolated from the traditional Chinese herb Danshen, has showed cardioprotective effect against IR injury through unknown mechanism. In this study, rat hearts were suspended in Langendorff instrument and perfused with Krebs-Henseleit (KH) buffer containing DSS for 60 minutes, followed by 30 minutes of global ischemia...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29246646/the-dialkyl-resorcinol-stemphol-disrupts-calcium-homeostasis-to-trigger-programmed-immunogenic-necrosis-in-cancer
#17
Seungwon Ji, Jin-Young Lee, Jan Schrör, Aloran Mazumder, Dong Man Jang, Sébastien Chateauvieux, Michael Schnekenburger, Che Ry Hong, Christo Christov, Hyoung Jin Kang, Youngjo Lee, Byung Woo Han, Kyu-Won Kim, Hee-Young Shin, Mario Dicato, Claudia Cerella, Gabriele M König, Barbora Orlikova, Marc Diederich
Stemphol (STP) is a novel druggable phytotoxin triggering mixed apoptotic and non-apoptotic necrotic-like cell death in human acute myeloid leukemia (AML). Use of several chemical inhibitors highlighted that STP-induced non-canonical programmed cell death was Ca2+-dependent but independent of caspases, poly (ADP-ribose) polymerase-1, cathepsin, or calpains. Similar to thapsigargin, STP led to increased cytosolic Ca2+ levels and computational docking confirmed binding of STP within the thapsigargin binding pocket of the sarco/endoplasmic reticulum (ER) Ca2+-ATPase (SERCA)...
December 12, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29238517/exogenous-h2s-restores-ischemic-post-conditioning-induced-cardioprotection-through-inhibiting-endoplasmic-reticulum-stress-in-the-aged-cardiomyocytes
#18
Weiming Sun, Jinxia Yang, Yuanzhou Zhang, Yuxin Xi, Xin Wen, Di Yuan, Yuehong Wang, Can Wei, Rui Wang, Lingyun Wu, Hongzhu Li, Changqing Xu
Background: A gasotransmitter hydrogen sulfide (H2S) plays an important physiological and pathological role in cardiovascular system. Ischemic post-conditioning (PC) provides cardioprotection in the young hearts but not in the aged hearts. Exogenous H2S restores PC-induced cardioprotection by inhibition of mitochondrial permeability transition pore opening and oxidative stress and increase of autophagy in the aged hearts. However, whether H2S contributes to the recovery of PC-induced cardioprotection via down-regulation of endoplasmic reticulum stress (ERS) in the aged hearts is unclear...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/29233966/from-atp-synthase-dimers-to-c-ring-conformational-changes-unified-model-of-the-mitochondrial-permeability-transition-pore
#19
Giuseppe Federico Amodeo, Maria de la Encarnacion Solesio Torregrosa, Evgeny V Pavlov
No abstract text is available yet for this article.
December 4, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29223733/mitochondrial-pore-opening-and-loss-of-ca2-exchanger-nclx-levels-occur-after-frataxin-depletion
#20
R Purroy, E Britti, F Delaspre, J Tamarit, J Ros
Frataxin-deficient neonatal rat cardiomyocytes and dorsal root ganglia neurons have been used as cell models of Friedreich ataxia. In previous work we show that frataxin depletion resulted in mitochondrial swelling and lipid droplet accumulation in cardiomyocytes, and compromised DRG neurons survival. Now, we show that these cells display reduced levels of the mitochondrial calcium transporter NCLX that can be restored by calcium-chelating agents and by external addition of frataxin fused to TAT peptide. Also, the transcription factor NFAT3, involved in cardiac hypertrophy and apoptosis, becomes activated by dephosphorylation in both cardiomyocytes and DRG neurons...
December 6, 2017: Biochimica et Biophysica Acta
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