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https://www.readbyqxmd.com/read/28628894/small-molecule-probes-for-cellular-death-machines
#1
REVIEW
Ying Li, Lihui Qian, Junying Yuan
The past decade has witnessed a significant expansion of our understanding about the regulated cell death mechanisms beyond apoptosis. The application of chemical biological approaches had played a major role in driving these exciting discoveries. The discovery and use of small molecule probes in cell death research has not only revealed significant insights into the regulatory mechanism of cell death but also provided new drug targets and lead drug candidates for developing therapeutics of human diseases with huge unmet need...
June 16, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28627418/alterations-in-neuronal-control-of-body-weight-and-anxiety-behavior-by-glutathione-peroxidase-4-deficiency
#2
Sonja C Schriever, Annemarie Zimprich, Katrin Pfuhlmann, Peter Baumann, Florian Giesert, Valentina Klaus, Dhiraj G Kabra, Ulrich Hafen, Artem Romanov, Matthias H Tschöp, Wolfgang Wurst, Marcus Conrad, Sabine M Hölter, Daniela Vogt Weisenhorn, Paul T Pfluger
Elevated levels of oxidative stress and neuronal inflammation in the hypothalamus or ventral midbrain, respectively, represent common denominators for obesity and Parkinson's Disease (PD). However, little is known about defense mechanisms that protect neurons in these regions from oxidative damage. Here, we aimed to assess whether murine Gpx4, a crucial antioxidant enzyme that protects neurons from membrane damage and ferroptosis, is critical for the protection from neuronal inflammation in two distinct pathophysiologic diseases, namely metabolic dysfunction in diet-induced obesity or PD...
June 13, 2017: Neuroscience
https://www.readbyqxmd.com/read/28616580/ferroptosis-like-death-in-plant-cells
#3
Megan Conlon, Scott J Dixon
Ferroptosis is an iron-dependent, oxidative, non-apoptotic form of cell death initially described in mammalian cells. We recently reported that a ferroptosis-like cell death process can be triggered by heat shock in Arabidopsis thaliana. Thus, ferroptosis may be a form of cell death conserved between animals and plants.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28613094/an-iron-hand-over-cancer-stem-cells
#4
Ahmed Hamaï, Tatiana Cañeque, Sebastian Müller, Trang Thi Mai, Antje Hienzsch, Christophe Ginestier, Emmanuelle Charafe-Jauffret, Patrice Codogno, Maryam Mehrpour, Raphaël Rodriguez
The paradigm of cancer stem cells (CSCs) defines the existence of cells exhibiting self-renewal and tumor-seeding capacity. These cells have been associated with tumor relapse and are typically resistant to conventional chemotherapeutic agents. Over the past decade, chemical biology studies have revealed a significant number of small molecules able to alter the proliferation of these cells in various settings. The natural product salinomycin has emerged as the most promising anti-CSC agent. However, an explicit mechanism of action has not yet been characterized, in particular due to the pleiotropic responses salinomycin is known for...
June 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28595877/lipoxygenase-inhibitors-protect-acute-lymphoblastic-leukemia-cells-from-ferroptotic-cell-death
#5
Lukas Probst, Jasmin Dächert, Barbara Schenk, Simone Fulda
Ferroptosis has recently been identified as a mode of programmed cell death. However, little is yet known about the signaling mechanisms. Here, we report that lipoxygenases (LOX) contribute to the regulation of RSL3-induced ferroptosis in acute lymphoblastic leukemia (ALL) cells. We show that the glutathione (GSH) peroxidase 4 (GPX4) inhibitor RSL3 triggers lipid peroxidation, production of reactive oxygen species (ROS) and cell death in ALL cells. All these events are impeded in the presence of Ferrostatin-1 (Fer-1), a small-molecule inhibitor of lipid peroxidation...
June 5, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28566503/heavy-metal-suicide
#6
Andreas Linkermann, Brent R Stockwell, Tom Vanden Berghe
In acute kidney injury (AKI), the majority of dying tubular cells succumbs to an iron-dependent form of regulated necrosis, referred to as ferroptosis. Ferroptosis is essentially mediated by iron-catalyzed lipid peroxidation upon GPX4 dysfunction. Heme oxygenase 1 (HO-1) is a master regulator of intracellular free iron due to the conversion of heme to iron, carbon monoxide, and biliverdin(12), and therefore represents a potential regulator of ferroptotic cell death. In this issue of AJP - Renal Physiology, Adedoyin et al...
May 31, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28553953/atf4-promotes-angiogenesis-and-neuronal-cell-death-and-confers-ferroptosis-in-a-xct-dependent-manner
#7
D Chen, Z Fan, M Rauh, M Buchfelder, I Y Eyupoglu, N Savaskan
Activating transcription factor 4 (ATF4) is a critical mediator of metabolic and oxidative homeostasis and cell survival. ATF4 is elevated in response to diverse microenvironmental stresses, including starvation, ER stress damages and exposure to toxic factors. Here we show that ATF4 expression fosters the malignancy of primary brain tumors (WHO grade III and IV gliomas) and increases proliferation and tumor angiogenesis. Hence, ATF4 expression promotes cell migration and anchorage-independent cell growth, whereas siRNA-mediated knockdown of ATF4 attenuates these features of malignancy in human gliomas...
May 29, 2017: Oncogene
https://www.readbyqxmd.com/read/28552631/ferroptosis-role-of-lipid-peroxidation-iron-and-ferritinophagy
#8
REVIEW
Gladys O Latunde-Dada
Ferroptosis is a form of regulated cell death that is dependent on iron and reactive oxygen species (ROS) and is characterized by lipid peroxidation. It is morphologically and biochemically distinct and disparate from other processes of cell death. As ferroptosis is induced by inhibition of cysteine uptake or inactivation of the lipid repair enzyme glutathione peroxidase 4 (GPX4), the process is favored by chemical or mutational inhibition of the cystine/glutamate antiporter and culminates in the accumulation of reactive oxygen species (ROS) in the form of lipid hydroperoxides...
August 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28551825/necroptosis-and-ferroptosis-are-alternative-cell-death-pathways-that-operate-in-acute-kidney-failure
#9
Tammo Müller, Christin Dewitz, Jessica Schmitz, Anna Sophia Schröder, Jan Hinrich Bräsen, Brent R Stockwell, James M Murphy, Ulrich Kunzendorf, Stefan Krautwald
Ferroptosis is a recently recognized caspase-independent form of regulated cell death that is characterized by the accumulation of lethal lipid ROS produced through iron-dependent lipid peroxidation. Considering that regulation of fatty acid metabolism is responsible for the membrane-resident pool of oxidizable fatty acids that undergo lipid peroxidation in ferroptotic processes, we examined the contribution of the key fatty acid metabolism enzyme, acyl-CoA synthetase long-chain family member 4 (ACSL4), in regulating ferroptosis...
May 27, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28545724/the-role-of-ca-2-in-cell-death-caused-by-oxidative-glutamate-toxicity-and-ferroptosis
#10
REVIEW
Pamela Maher, Klaus van Leyen, Partha Narayan Dey, Birgit Honrath, Amalia Dolga, Axel Methner
Ca(2+) ions play a fundamental role in cell death mediated by oxidative glutamate toxicity or oxytosis, a form of programmed cell death similar and possibly identical to other forms of cell death like ferroptosis. Ca(2+) influx from the extracellular space occurs late in a cascade characterized by depletion of the intracellular antioxidant glutathione, increases in cytosolic reactive oxygen species and mitochondrial dysfunction. Here, we aim to compare oxidative glutamate toxicity with ferroptosis, address the signaling pathways that culminate in Ca(2+) influx and cell death and discuss the proteins that mediate this...
May 12, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28525763/principles-of-chemical-biology-from-antibiotic-resistance-to-rna-targeted-therapy-via-autoxidation-and-lipid-droplets
#11
(no author information available yet)
This month: Ribosome mutations and multi-antibiotic resistance, role of autoxidation in ferroptosis, ceramide metabolism, and finding RNA drug targets.
May 18, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28515173/heme-oxygenase-1-mitigates-ferroptosis-in-renal-proximal-tubule-cells
#12
Oreoluwa Adedoyin, Ravindra Boddu, Amie M Traylor, Jeremie M Lever, Subhashini Bolisetty, James George, Anupam Agarwal
Ferroptosis is an iron-dependent form of regulated, non-apoptotic cell death, which contributes to damage in models of acute kidney injury (AKI). Heme oxygenase-1 (HO-1) is a cytoprotective enzyme induced in response to cellular stress, and is protective against AKI due to its anti-apoptotic and anti-inflammatory properties. However, the role of HO-1 in regulating ferroptosis is unclear. The purpose of this study was to elucidate the role of HO-1 in regulating ferroptotic cell death in renal proximal tubule cells (PTCs)...
May 17, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28494534/ferroptosis-a-novel-anti-tumor-action-for-cisplatin
#13
Jipeng Guo, Bingfei Xu, Qi Han, Hongxia Zhou, Yun Xia, Chongwen Gong, Xiaofang Dai, Zhenyu Li, Gang Wu
Purpose: Ferroptosis is a new mode of regulated cell death, which is completely distinct from other cell death modes based on morphological, biochemical, and genetic criteria. This study evaluated the therapeutic role of ferroptosis in classic chemotherapy drugs, including the underlying mechanism. Materials and Methods: Cell viability was detected by using the Methylthiazoltetrazlium dye uptake method. RNAi was used to knockout iron-responsive element binding protein 2, and PCR, western blot was used to evaluate the efficiency...
May 10, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28489094/theoretical-insights-into-the-mechanism-of-ferroptosis-suppression-via-inactivation-of-a-lipid-peroxide-radical-by-liproxstatin-1
#14
Xiehuang Sheng, Chao Shan, Jianbiao Liu, Jintong Yang, Bin Sun, Dezhan Chen
Ferroptosis is a recently discovered iron-dependent form of non-apoptotic cell death caused by the accumulation of membrane lipid peroxidation products, which is involved in various pathological conditions of the brain, kidney, liver and heart. A potent spiroquinoxalinamine derivative named liproxstatin-1 is discovered by high-throughput screening, which is able to suppress ferroptosis via lipid peroxide scavenging in vivo. Thus, molecular simulations, density functional theory (DFT) and variational transition-state theory with a small-curvature tunneling (SCT) coefficient are utilized to elucidate the detailed mechanisms of inactivation of a lipid peroxide radical by liproxstatin-1...
May 24, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28470518/ferroptosis-and-cell-death-analysis-by-flow-cytometry
#15
Daishi Chen, Ilker Y Eyupoglu, Nicolai Savaskan
Cell death and its recently discovered regulated form ferroptosis are characterized by distinct morphological, electrophysiological, and pharmacological features. In particular ferroptosis can be induced by experimental compounds and clinical drugs (i.e., erastin, sulfasalazine, sorafenib, and artesunate) in various cell types and cancer cells. Pharmacologically, this cell death process can be inhibited by iron chelators and lipid peroxidation inhibitors. Relevance of this specific cell death form has been found in different pathological conditions such as cancer, neurotoxicity, neurodegeneration, and ischemia...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28462584/gpx4-lipid-peroxidation-and-cell-death-discoveries-rediscoveries-and-open-issues
#16
Matilde Maiorino, Marcus Conrad, Fulvio Ursini
SIGNIFICANCE: Iron-dependent lipid peroxidation is a complex oxidative process where phospholipid hydroperoxides (PLOOH) are produced in membranes and finally transformed into a series of decomposition products, some of which are endowed with biological activity. It is specifically prevented by glutathione peroxidase 4 (GPx4), the selenoenzyme that reduces PLOOH by glutathione (GSH). PLOOH is both a product and the major initiator of peroxidative chain reactions, as well as an activator of lipoxygenases...
May 30, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28462529/ferroptosis-bug-or-feature
#17
REVIEW
Scott J Dixon
Ferroptosis is an iron-dependent, oxidative form of non-apoptotic cell death. This form of cell death does not share morphological, biochemical, or genetic similarities with classic necrosis, necroptosis, parthanatos, or other forms of non-apoptotic cell death. Ferroptosis can be triggered by depleting the cell of the amino acid cysteine, or by inhibiting the phospholipid hydroperoxidase glutathione peroxidase 4 (GPX4). Why certain stimuli trigger ferroptosis instead of another form of cell death, and whether this process could be adaptive in vivo, are two major unanswered questions concerning this process...
May 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28462528/the-in-vivo-evidence-for-regulated-necrosis
#18
REVIEW
Wulf Tonnus, Andreas Linkermann
Necrosis is a hallmark of several widespread diseases or their direct complications. In the past decade, we learned that necrosis can be a regulated process that is potentially druggable. RIPK3- and MLKL-mediated necroptosis represents by far the best studied pathway of regulated necrosis. During necroptosis, the release of damage-associated molecular patterns (DAMPs) drives a phenomenon referred to as necroinflammation, a common consequence of necrosis. However, most studies of regulated necrosis investigated cell lines in vitro in a cell autonomous manner, which represents a non-physiological situation...
May 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28434137/cholesterol-hydroperoxide-generation-translocation-and-reductive-turnover-in-biological-systems
#19
Albert W Girotti, Witold Korytowski
Cholesterol is like other unsaturated lipids in being susceptible to peroxidative degradation upon exposure to strong oxidants like hydroxyl radical or peroxynitrite generated under conditions of oxidative stress. In the eukaryotic cell plasma membrane, where most of the cellular cholesterol resides, peroxidation leads to membrane structural and functional damage from which pathological states may arise. In low density lipoprotein, cholesterol and phospholipid peroxidation have long been associated with atherogenesis...
April 22, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28433662/iron-and-thiol-redox-signaling-in-cancer-an-exquisite-balance-to-escape-ferroptosis
#20
REVIEW
Shinya Toyokuni, Fumiya Ito, Kyoko Yamashita, Yasumasa Okazaki, Shinya Akatsuka
Epidemiological data indicate a constant worldwide increase in cancer mortality, although the age of onset is increasing. Recent accumulation of genomic data on human cancer via next-generation sequencing confirmed that cancer is a disease of genome alteration. In many cancers, the Nrf2 transcription system is activated via mutations either in Nrf2 or Keap1 ubiquitin ligase, leading to persistent activation of the genes with antioxidative functions. Furthermore, deep sequencing of passenger mutations is clarifying responsible cancer causative agent(s) in each case, including aging, APOBEC activation, smoking and UV...
April 19, 2017: Free Radical Biology & Medicine
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