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1دورية أكاديمية
المصدر: BMC Research Notes, Vol 14, Iss 1, Pp 1-7 (2021)
مصطلحات موضوعية: BAX, Intrinsic apoptosis, Mitochondrial dysfunction, Mitochondrial outer membrane permeabilization, Mitochondrial fragmentation, Elamipretide (SS31), Medicine, Biology (General), QH301-705.5, Science (General), Q1-390
الوصف: Abstract Objective Elamipretide (SS31) is a mitochondria-targeted peptide that has reported functions of stabilizing mitochondrial cristae structure and improving mitochondrial bioenergetics. Several studies have documented cell protective features of this peptide, including impairment of intrinsic apoptosis by inhibiting the recruitment and activation of the pro-apoptotic BAX protein. We used live-cell imaging of ARPE-19 cells expressing fluorescently labeled BAX, cytochrome c, and a mitochondrial marker to investigate the effect of elamipretide on the kinetics of BAX recruitment, mitochondrial outer membrane permeabilization (as a function of cytochrome c release), and mitochondrial fragmentation, respectively. Result In nucleofected and plated ARPE-19 cells, elamipretide accelerated the formation of larger mitochondria. In the presence of the apoptotic stimulator, staurosporine, cells treated with elamipretide exhibited moderately slower rates of BAX recruitment. Peptide treatment, however, did not significantly delay the onset of BAX recruitment or the final total amount of BAX that was recruited. Additionally, elamipretide showed no impairment or delay of cytochrome c release or mitochondrial fragmentation, two events associated with normal BAX activation during cell death. These results indicate that the protective effect of elamipretide is not at the level of BAX activity to induce pro-apoptotic mitochondrial dysfunction after the initiation of staurosporine-induced apoptosis.
وصف الملف: electronic resource
العلاقة: https://doaj.org/toc/1756-0500Test
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2دورية أكاديمية
المؤلفون: Joshua A. Grosser (10853724), Rachel L. Fehrman (10853727), Dennis Keefe (8190210), Martin Redmon (10853730), Robert W. Nickells (10853733)
مصطلحات موضوعية: Biophysics, Biochemistry, Cell Biology, Immunology, Cancer, Environmental Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, BAX, Intrinsic apoptosis, Mitochondrial dysfunction, Mitochondrial outer membrane permeabilization, Mitochondrial fragmentation, Elamipretide (SS31)
الوصف: Additional file 4: Table S1. Elamipretide does not delay the onset of BAX recruitment.
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3
المصدر: BMC Research Notes
BMC Research Notes, Vol 14, Iss 1, Pp 1-7 (2021)مصطلحات موضوعية: 0301 basic medicine, Programmed cell death, Science (General), QH301-705.5, Mitochondrial outer membrane permeabilization, Cell, Apoptosis, Mitochondrion, Elamipretide (SS31), General Biochemistry, Genetics and Molecular Biology, Q1-390, 03 medical and health sciences, 0302 clinical medicine, medicine, Staurosporine, Biology (General), bcl-2-Associated X Protein, biology, Chemistry, Cytochrome c, Intrinsic apoptosis, General Medicine, Elamipretide, Mitochondria, Cell biology, Research Note, 030104 developmental biology, medicine.anatomical_structure, BAX, biology.protein, Medicine, Mitochondrial fragmentation, Mitochondrial dysfunction, Oligopeptides, 030217 neurology & neurosurgery, medicine.drug
الوصف: Objective Elamipretide (SS31) is a mitochondria-targeted peptide that has reported functions of stabilizing mitochondrial cristae structure and improving mitochondrial bioenergetics. Several studies have documented cell protective features of this peptide, including impairment of intrinsic apoptosis by inhibiting the recruitment and activation of the pro-apoptotic BAX protein. We used live-cell imaging of ARPE-19 cells expressing fluorescently labeled BAX, cytochrome c, and a mitochondrial marker to investigate the effect of elamipretide on the kinetics of BAX recruitment, mitochondrial outer membrane permeabilization (as a function of cytochrome c release), and mitochondrial fragmentation, respectively. Result In nucleofected and plated ARPE-19 cells, elamipretide accelerated the formation of larger mitochondria. In the presence of the apoptotic stimulator, staurosporine, cells treated with elamipretide exhibited moderately slower rates of BAX recruitment. Peptide treatment, however, did not significantly delay the onset of BAX recruitment or the final total amount of BAX that was recruited. Additionally, elamipretide showed no impairment or delay of cytochrome c release or mitochondrial fragmentation, two events associated with normal BAX activation during cell death. These results indicate that the protective effect of elamipretide is not at the level of BAX activity to induce pro-apoptotic mitochondrial dysfunction after the initiation of staurosporine-induced apoptosis.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6b4af6c2b33b3bbc0d549b091141f275Test
https://doi.org/10.1186/s13104-021-05613-9Test -
4صورة
المؤلفون: Joshua A. Grosser (10853724), Rachel L. Fehrman (10853727), Dennis Keefe (8190210), Martin Redmon (10853730), Robert W. Nickells (10853733)
مصطلحات موضوعية: Biophysics, Biochemistry, Cell Biology, Immunology, Cancer, Environmental Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, BAX, Intrinsic apoptosis, Mitochondrial dysfunction, Mitochondrial outer membrane permeabilization, Mitochondrial fragmentation, Elamipretide (SS31)
الوصف: Additional file 1: Figure S1. Elamipretide stimulates a more rapid increase in mitochondrial volume. Mitochondria were identified in ARPE-19 cells nucleofected with a plasmid carrying a mitoBFP fusion protein. Nucelofected cells were plated in chamber slides, allowed to incubate for 24 h and then imaged for another 20 h. (A) Confocal image of a cell imaged at 1 h and then again at 7 h (B) after exposure to 1 µM elamipretide. Only the BFP channel is shown. Over time, mitochondria appear more filamentous and elongated. Size bar = 10 µm. (C) Quantification of average mitochondrial volumes of cells taken from both time-lapse and static images. The scatterplot shows data collected from individual cells at each time point (mean ± SD also indicated). Mitochondrial volume was measured in 3D reconstructions of confocal images using Imaris 9.2 imaging software. Elamipretide treated cells exhibit significantly greater mitochondrial volumes at 4 and 7 h after exposure to the peptide (*P = 0.005 and **P = 0.002, respectively). By 20 h, both treatment groups exhibit similarly larger mitochondria (P = 0.207)
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5صورة
المؤلفون: Joshua A. Grosser (10853724), Rachel L. Fehrman (10853727), Dennis Keefe (8190210), Martin Redmon (10853730), Robert W. Nickells (10853733)
مصطلحات موضوعية: Biophysics, Biochemistry, Cell Biology, Immunology, Cancer, Environmental Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, BAX, Intrinsic apoptosis, Mitochondrial dysfunction, Mitochondrial outer membrane permeabilization, Mitochondrial fragmentation, Elamipretide (SS31)
الوصف: Additional file 2: Figure S2. Time lapse images of a vehicle-treated ARPE-19 cell undergoing apoptosis. In this example, SMAC-GFP was used to show mitochondrial outer membrane permeabilization. Size bar = 7 µm.
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6صورة
المؤلفون: Joshua A. Grosser (10853724), Rachel L. Fehrman (10853727), Dennis Keefe (8190210), Martin Redmon (10853730), Robert W. Nickells (10853733)
مصطلحات موضوعية: Biophysics, Biochemistry, Cell Biology, Immunology, Cancer, Environmental Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, BAX, Intrinsic apoptosis, Mitochondrial dysfunction, Mitochondrial outer membrane permeabilization, Mitochondrial fragmentation, Elamipretide (SS31)
الوصف: Additional file 3: Figure S3. Temporal assessment of cells undergoing mCherry-BAX recruitment during live-cell imaging experiments. Data collected from 13 imaging experiments are graphed. Each point represents a single cell. The horizontal lines indicate the duration of the imaging session and the points on each line indicate cells that underwent BAX recruitment during that session. Points represented in the column labeled “Other” represent cells that were set up for imaging but did not convert cytosolic BAX to punctate BAX.
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المؤلفون: Joerg Stetefeld, Joanna Rzeszowska-Wolny, Mayur V. Jain, Artur Cieślar-Pobuda, Wiem Chaabane, Saeid Ghavami, Marek J. Łos, Mohamed El-Gazzah, Mehrdad Rafat
المصدر: Neoplasia: An International Journal for Oncology Research, Vol 16, Iss 9, Pp 679-693 (2014)
Neoplasia (New York, N.Y.)مصطلحات موضوعية: Cytoplasm, Cancer Research, TMRM, Tetramethylrhodamine methyl ester perchlorate0, HGV-Apoptin, Human gyrovirus apoptin, Apoptosis, MOMP, Mitochondrial outer membrane permeabilization, Mitochondrial apoptosis-induced channel, AIF, Nur77, Annan medicinsk grundvetenskap, AIF, Apoptosis inducing factor, Nuclear Receptor Subfamily 4, Group A, Member 1, Gyrovirus, BCL-XL, B-cell lymphoma extra-large, DISC, Death-inducing signal complex, FADD, Other Basic Medicine, Membrane Potential, Mitochondrial, biology, Apoptosis Inducing Factor, Cytochromes c, virus diseases, Receptors, Death Domain, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, mitochondrial pathway, Mitochondria, Cell biology, Protein Transport, Proto-Oncogene Proteins c-bcl-2, Caspases, Apoptosis-inducing factor, Signal Transduction, CAV-Apoptin, Chicken anemia virus apoptin, Programmed cell death, cyt c, cytochrome c, caspase, Bcl-xL, Models, Biological, lcsh:RC254-282, Article, Cell Line, Viral Proteins, death receptors, Humans, 7AAD, 7-amino-actinomycin D, FADD, Fas-associated death domain, Death domain, Intrinsic apoptosis, MEF, Mouse embryonic fibroblast, cytc, digestive system diseases, Apoptin, biology.protein, Apoptosome
الوصف: The human gyrovirus derived protein Apoptin (HGV-Apoptin) a homologue of the chicken anemia virus Apoptin (CAV-Apoptin), a protein with high cancer cells selective toxicity, triggers apoptosis selectively in cancer cells. In this paper, we show that HGV-Apoptin acts independently from the death receptor pathway as it induces apoptosis in similar rates in Jurkat cells deficient in either FADD (fas-associated death domain) function or caspase-8 (key players of the extrinsic pathway) and their parental clones. HGV-Apoptin induces apoptosis via the activation of the mitochondrial intrinsic pathway. It induces both mitochondrial inner and outer membrane permebilization, characterized by the loss of the mitochondrial potential and the release into cytoplasm of the pro-apoptotic molecules including apoptosis inducing factor and cytochrome c. HGV-Apoptin acts via the apoptosome, as lack of expression of apoptotic protease-activating factor 1 in murine embryonic fibroblast strongly protected the cells from HGV-Apoptin–induced apoptosis. Moreover, QVD-oph a broad-spectrum caspase inhibitor delayed HGV-Apoptin–induced death. On the other hand, overexpression of the anti-apoptotic BCL-XL confers resistance to HGV-Apoptin–induced cell death. In contrast, cells that lack the expression of the pro-apoptotic BAX and BAK are protected from HGV-Apoptin induced apoptosis. Furthermore, HGV-Apoptin acts independently from p53 signal but triggers the cytoplasmic translocation of Nur77. Taking together these data indicate that HGV-Apoptin acts through the mitochondrial pathway, in a caspase-dependent manner but independently from the death receptor pathway.
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4ff91e1764b6bc1727600d6c646b3f55Test
https://doi.org/10.1016/j.neo.2014.08.001Test -
8
المؤلفون: Lorenzo Galluzzi, Sharad Kumar, Alejandro López-Soto, Guido Kroemer
المساهمون: Galluzzi, Lorenzo, López-Soto, Alejandro, Kumar, Sharad, Kroemer, Guido
مصطلحات موضوعية: 0301 basic medicine, Programmed cell death, Necroptosis, Immunology, necroptosis, Caspase 8, damage-associated molecular pattern, 03 medical and health sciences, inflammasome, Immunology and Allergy, Animals, Homeostasis, Humans, Caspase, biology, Cell Death, pyroptosis, Intrinsic apoptosis, Pyroptosis, apoptosome, Cell biology, 030104 developmental biology, Infectious Diseases, Apoptosis, Caspases, biology.protein, Apoptosome, mitochondrial outer-membrane permeabilization, Signal Transduction
الوصف: Some forms of regulated cell death, such as apoptosis, are precipitated by the activation of cysteine proteases of the caspase family, including caspase 8, 9, and 3. Other caspases, such as caspase 1 and 4, are well known for their pro-inflammatory functions but regulate cell death in a limited number of pathophysiological settings. Accumulating evidence suggests that the most conserved function of mammalian caspases is not to control cell death sensu stricto, but to regulate inflammatory and immune reactions to dying cells and infectious challenges. Here, we review the molecular and cellular mechanisms though which mammalian caspases connect cell-death signaling to the maintenance of organismal homeostasis. Refereed/Peer-reviewed
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ea5c1b8615d2cbe0b63375f526741511Test
https://hdl.handle.net/11541.2/117531Test -
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المؤلفون: Peter K. Sorger, Sabrina L. Spencer
المصدر: Cell. 144(6):926-939
مصطلحات موضوعية: Programmed cell death, Mitochondrial outer membrane permeabilization, Effector Caspases, Biochemistry, Genetics and Molecular Biology(all), Cell, Intrinsic apoptosis, Apoptosis, Disease, Biology, Models, Biological, General Biochemistry, Genetics and Molecular Biology, Article, Cell biology, medicine.anatomical_structure, Caspases, Mitochondrial Membranes, medicine, Animals, Humans, Single-Cell Analysis, Systems pharmacology
الوصف: Cell death plays an essential role in the development of tissues and organisms, the etiology of disease, and the responses of cells to therapeutic drugs. Here we review progress made over the last decade in using mathematical models and quantitative, often single-cell, data to study apoptosis. We discuss the delay that follows exposure of cells to prodeath stimuli, control of mitochondrial outer membrane permeabilization, switch-like activation of effector caspases, and variability in the timing and probability of death from one cell to the next. Finally, we discuss challenges facing the fields of biochemical modeling and systems pharmacology.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::08ce9be8349bfaa5944b05d447810f39Test
النص الكامل