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Ceramide autophagy

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https://www.readbyqxmd.com/read/30081476/lipid-droplets-in-cancer-guardians-of-fat-in-a-stressful-world
#1
REVIEW
Toni Petan, Eva Jarc, Maida Jusović
Cancer cells possess remarkable abilities to adapt to adverse environmental conditions. Their survival during severe nutrient and oxidative stress depends on their capacity to acquire extracellular lipids and the plasticity of their mechanisms for intracellular lipid synthesis, mobilisation, and recycling. Lipid droplets, cytosolic fat storage organelles present in most cells from yeast to men, are emerging as major regulators of lipid metabolism, trafficking, and signalling in various cells and tissues exposed to stress...
August 3, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/30060813/sphingolipids-as-regulators-of-autophagy-and-endocytic-trafficking
#2
Megan M Young, Hong-Gang Wang
Macroautophagy (herein referred to as autophagy) is a highly conserved stress response that engulfs damaged proteins, lipids, and/or organelles within double-membrane vesicles called autophagosomes for lysosomal degradation. Dysregulated autophagy is a hallmark of cancer; and thus, there is great interest in modulating autophagy for cancer therapy. Sphingolipids regulate each step of autophagosome biogenesis with roles for sphingolipid metabolites and enzymes spanning from the initial step of de novo ceramide synthesis to the sphingosine-1-phosphate lyase 1-mediated exit from the sphingolipid pathway...
2018: Advances in Cancer Research
https://www.readbyqxmd.com/read/30060809/ceramide-signaling-and-p53-pathways
#3
Kristen A Jeffries, Natalia I Krupenko
Ceramides, important players in signal transduction, interact with multiple cellular pathways, including p53 pathways. However, the relationship between ceramide and p53 is very complex, and mechanisms underlying their coregulation are diverse and not fully characterized. The role of p53, an important cellular regulator and a transcription factor, is linked to its tumor suppressor function. Ceramides are involved in the regulation of fundamental processes in cancer cells including cell death, proliferation, autophagy, and drug resistance...
2018: Advances in Cancer Research
https://www.readbyqxmd.com/read/30059758/chemosensitivity-of-human-colon-cancer-cells-is-influenced-by-a-p53-dependent-enhancement-of-ceramide-synthase-5-and-induction-of-autophagy
#4
Sebastian Brachtendorf, Ruth Anna Wanger, Kerstin Birod, Dominique Thomas, Sandra Trautmann, Marthe-Susanna Wegner, Dominik C Fuhrmann, Bernhard Brüne, Gerd Geisslinger, Sabine Grösch
Resistance against chemotherapy is a life-threatening complication in colon cancer therapy. To increase response rate, new additional targets that contribute to chemoresistance are still needed to be explored. Ceramides, which belong to the group of sphingolipids, are well-known regulators of cell death and survival, respectively. Here, we show that in human wild-type (wt ) p53 HCT-116 colon cancer cells treatment with oxaliplatin or 5-fluorouracil (5-FU) leads to a strong increase in ceramide synthase 5 (CerS5) expression and C16:0 -ceramide levels, which was not shown in HCT-116 lacking p53 expression (HCT-116 p53-/- )...
July 27, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/30054909/cers6-regulates-cisplatin-resistance-in-oral-squamous-cell-carcinoma-by-altering-mitochondrial-fission-and-autophagy
#5
Shengjiao Li, Yangou Wu, Yunpeng Ding, Miao Yu, Zexin Ai
Chemoresistance remains a challenge in the effective treatment of solid tumors, including oral squamous cell carcinoma (OSCC). Mitochondrial dynamics and autophagy have recently been implicated in the chemoresistance of cancer cells. The neutralization of ceramide is also associated with multidrug resistance, and ceramide synthase 6 (CerS6) is known to induce apoptosis. However, whether CerS6 regulates chemoresistance in OSCC is not clearly understood. Therefore, we investigated the role of CerS6 in the susceptibility of OSCC cells to cisplatin...
July 27, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/30040861/novel-oxazolinoanthracyclines-as-tumor-cell-growth-inhibitors-contribution-of-autophagy-and-apoptosis-in-solid-tumor-cells-death
#6
Aneta Rogalska, Arkadiusz Gajek, Małgorzata Łukawska, Irena Oszczapowicz, Agnieszka Marczak
Chemical modification of known, effective drugs are one method to improve the chemotherapy of tumors. We reported ability of oxazoline analogs of doxorubicin (O-DOX) and daunorubicin (O-DAU) to induce apoptosis and autophagy in ovarian and liver cancer cells. Reactive oxygen and nitrogen species (ROS and RNS, respectively), together with intracellular calcium-mediated downstream signaling, are essential for the anticancer effect of these new anthracycline analogs. The changes of mitochondrial membrane potential and induction of the ceramide pathway suggests that these compounds induce cell death by apoptosis...
2018: PloS One
https://www.readbyqxmd.com/read/30038230/antidepressants-act-by-inducing-autophagy-controlled-by-sphingomyelin-ceramide
#7
Anne Gulbins, Fabian Schumacher, Katrin Anne Becker, Barbara Wilker, Matthias Soddemann, Francesco Boldrin, Christian P Müller, Michael J Edwards, Michael Goodman, Charles C Caldwell, Burkhard Kleuser, Johannes Kornhuber, Ildiko Szabo, Erich Gulbins
Major depressive disorder (MDD) is a common and severe disease characterized by mood changes, somatic alterations, and often suicide. MDD is treated with antidepressants, but the molecular mechanism of their action is unknown. We found that widely used antidepressants such as amitriptyline and fluoxetine induce autophagy in hippocampal neurons via the slow accumulation of sphingomyelin in lysosomes and Golgi membranes and of ceramide in the endoplasmic reticulum (ER). ER ceramide stimulates phosphatase 2A and thereby the autophagy proteins Ulk, Beclin, Vps34/Phosphatidylinositol 3-kinase, p62, and Lc3B...
July 23, 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/30031388/%C3%AE-tocotrienol-feeding-modulates-gene-expression-of-eif2-mtor-protein-ubiquitination-through-multiple-signaling-pathways-in-chronic-hepatitis-c-patients
#8
Asaf A Qureshi, Dilshad A Khan, Shahida Mushtaq, Shui Qing Ye, Min Xiong, Nilofer Qureshi
BACKGROUND: δ-Tocotrienol is a naturally occurring proteasome inhibitor, which has the capacity to inhibit proliferation and induce apoptosis in several cancer cells obtained from several organs of humans, and other cancer cell lines. Moreover, results of plasma total mRNAs after δ-tocotrienol feeding to hepatitis C patients revealed significant inhibition in the expression of pro-inflammatory cytokines (TNF-α, VCAM1, proteasome subunits) and induction in the expression of ICAM1 and IFN-γ after post-treatment...
July 21, 2018: Lipids in Health and Disease
https://www.readbyqxmd.com/read/30017509/phenotypic-and-lipidomic-characterization-of-primary-human-epidermal-keratinocytes-exposed-to-simulated-solar-uv-radiation
#9
Núria Dalmau, Nathalie Andrieu-Abadie, Romà Tauler, Carmen Bedia
BACKGROUND: Ultraviolet (UV) radiation is known to be one of the most important environmental hazards acting on the skin. The most part of UV radiation is absorbed in the epidermis, where keratinocytes are the most abundant and exposed cell type. Lipids have an important role in skin biology, not only for their important contribution to the maintenance of the permeability barrier but also for the production and storage of energy, membrane organization and cell signalling functions. However, the effects on the lipid composition of keratinocytes under UV radiation are little explored...
July 10, 2018: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29956204/pathogenesis-of-nash-how-metabolic-complications-of-overnutrition-favour-lipotoxicity-and-pro-inflammatory-fatty-liver-disease
#10
Geoffrey C Farrell, Fahrettin Haczeyni, Shivakumar Chitturi
Overnutrition, usually with obesity and genetic predisposition, lead to insulin resistance, which is an invariable accompaniment of nonalcoholic fatty liver disease (NAFLD). The associated metabolic abnormalities, pre- or established diabetes, hypertension and atherogenic dyslipidemia (clustered as metabolic syndrome) tend to be worse for nonalcoholic steatohepatitis (NASH), revealing it as part of a continuum of metabolic pathogenesis. The origins of hepatocellular injury and lobular inflammation which distinguish NASH from simple steatosis have intrigued investigators, but it is now widely accepted that NASH results from liver lipotoxicity...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29867196/activation-of-neutral-sphingomyelinase-2-by-starvation-induces-cell-protective-autophagy-via-an-increase-in-golgi-localized-ceramide
#11
Moon Jung Back, Hae Chan Ha, Zhicheng Fu, Jong Min Choi, Yongwei Piao, Jong Hoon Won, Ji Min Jang, In Chul Shin, Dae Kyong Kim
Autophagy is essential for optimal cell function and survival, and the entire process accompanies membrane dynamics. Ceramides are produced by different enzymes at different cellular membrane sites and mediate differential signaling. However, it remains unclear which ceramide-producing pathways/enzymes participate in autophagy regulation under physiological conditions such as nutrient starvation, and what the underlying mechanisms are. In this study, we demonstrate that among ceramide-producing enzymes, neutral sphingomyelinase 2 (nSMase2) plays a key role in autophagy during nutrient starvation...
June 4, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29806001/a-ceramide-regulated-element-in-the-late-endosomal-protein-laptm4b-controls-amino-acid-transporter-interaction
#12
Kecheng Zhou, Andrea Dichlberger, Hector Martinez-Seara, Thomas K M Nyholm, Shiqian Li, Young Ah Kim, Ilpo Vattulainen, Elina Ikonen, Tomas Blom
Membrane proteins are functionally regulated by the composition of the surrounding lipid bilayer. The late endosomal compartment is a central site for the generation of ceramide, a bioactive sphingolipid, which regulates responses to cell stress. The molecular interactions between ceramide and late endosomal transmembrane proteins are unknown. Here, we uncover in atomistic detail the ceramide interaction of Lysosome Associated Protein Transmembrane 4B (LAPTM4B), implicated in ceramide-dependent cell death and autophagy, and its functional relevance in lysosomal nutrient signaling...
May 23, 2018: ACS Central Science
https://www.readbyqxmd.com/read/29785744/fumonisin-b1-actuates-oxidative-stress-associated-colonic-damage-via-apoptosis-and-autophagy-activation-in-murine-model
#13
Sang Ho Kim, Mahendra Pal Singh, Chanchal Sharma, Sun Chul Kang
In the present study, we investigated the cytotoxic mechanism of Fumonisin B1 (FB1) in mice colonic region in a time course manner. Herein, after consecutive 4 days of exposure to FBI (2.5 mg/kg body weight), we observed disintegration of mice colon, as evidenced by histopathological analysis. FB1 significantly increased alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase activities in serum and plasma, decreased ceramide level, increased sphinganine level, and increased lipid peroxidase level along with the breakdown of the antioxidant system...
May 22, 2018: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/29746165/a-lysosome-plasma-membrane-sphingolipid-axis-linking-lysosomal-storage-to-cell-growth-arrest
#14
Maura Samarani, Nicoletta Loberto, Giulia Soldà, Letizia Straniero, Rosanna Asselta, Stefano Duga, Giulia Lunghi, Fabio A Zucca, Laura Mauri, Maria Grazia Ciampa, Domitilla Schiumarini, Rosaria Bassi, Paola Giussani, Elena Chiricozzi, Alessandro Prinetti, Massimo Aureli, Sandro Sonnino
Lysosomal accumulation of undegraded materials is a common feature of lysosomal storage diseases, neurodegenerative disorders, and the aging process. To better understand the role of lysosomal storage in the onset of cell damage, we used human fibroblasts loaded with sucrose as a model of lysosomal accumulation. Sucrose-loaded fibroblasts displayed increased lysosomal biogenesis followed by arrested cell proliferation. Notably, we found that reduced lysosomal catabolism and autophagy impairment led to an increase in sphingolipids ( i...
May 10, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29579237/acid-ceramidase-inhibition-ameliorates-%C3%AE-synuclein-accumulation-upon-loss-of-gba1-function
#15
Myung Jong Kim, Sohee Jeon, Lena F Burbulla, Dimitri Krainc
GBA1 encodes the lysosomal enzyme β-glucocerebrosidase (GCase) which converts glucosylceramide into ceramide and glucose. Mutations in GBA1 lead to Gaucher's disease and are a major risk factor for Parkinson's disease (PD) and Dementia with Lewy bodies (DLB), synucleinopathies characterized by accumulation of intracellular α-synuclein. In this study, we examined whether decreased ceramide that is observed in GCase-deficient cells contributes to α-synuclein accumulation. We demonstrated that deficiency of GCase leads to a reduction of C18-ceramide species and altered intracellular localization of Rab8a, a small GTPase implicated in secretory autophagy, that contributed to impaired secretion of α-synuclein and accumulation of intracellular α-synuclein...
June 1, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29463805/ceramide-induced-bok-promotes-mitochondrial-fission-in-preeclampsia
#16
Jonathan Ausman, Joelcio Abbade, Leonardo Ermini, Abby Farrell, Andrea Tagliaferro, Martin Post, Isabella Caniggia
Mitochondria are in a constant balance of fusing and dividing in response to cellular cues. Fusion creates healthy mitochondria, whereas fission results in removal of non-functional organelles. Changes in mitochondrial dynamics typify several human diseases. However, the contribution of mitochondrial dynamics to preeclampsia, a hypertensive disorder of pregnancy characterized by placental cell autophagy and death, remains unknown. Herein, we show that the mitochondrial dynamic balance in preeclamptic placentae is tilted toward fission (increased DRP1 expression/activation and decreased OPA1 expression)...
February 20, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29411122/dihydroceramide-desaturase-1-inhibitors-reduce-amyloid-%C3%AE-levels-in-primary-neurons-from-an-alzheimer-s-disease-transgenic-model
#17
Lara Ordóñez-Gutiérrez, Irene Benito-Cuesta, José Luis Abad, Josefina Casas, Gemma Fábrias, Francisco Wandosell
PURPOSE: The induction of autophagy has recently been explored as a promising therapeutic strategy to combat Alzheimer's disease. Among many other factors, there is evidence that ceramides/dihydroceramides act as mediators of autophagy, although the exact mechanisms underlying such effects are poorly understood. Here, we describe how two dihydroceramide desaturase inhibitors (XM461 and XM462) trigger autophagy and reduce amyloid secretion by neurons. METHODS: Neurons isolated from wild-type and APP/PS1 transgenic mice were exposed to the two dihydroceramide desaturase inhibitors to assess their effect on these cell's protein and lipid profiles...
February 6, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29378782/inhibition-of-acid-sphingomyelinase-disrupts-lynus-signaling-and-triggers-autophagy
#18
Matthew J Justice, Irina Bronova, Kelly S Schweitzer, Christophe Poirier, Janice S Blum, Evgeny V Berdyshev, Irina Petrache
Activation of the lysosomal ceramide-producing enzyme, acid sphingomyelinase (ASM), by various stresses is centrally involved in cell death and has been implicated in autophagy. We set out to investigate the role of the baseline ASM activity in maintaining physiological functions of lysosomes, focusing on the lysosomal nutrient-sensing complex (LYNUS), a lysosomal membrane-anchored multiprotein complex that includes mammalian target of rapamycin (mTOR) and transcription factor EB (TFEB). ASM inhibition with imipramine or sphingomyelin phosphodiesterase 1 ( SMPD1 ) siRNA in human lung cells, or by transgenic Smpd1 +/- haploinsufficiency of mouse lungs, markedly reduced mTOR- and P70-S6 kinase (Thr 389)-phosphorylation and modified TFEB in a pattern consistent with its activation...
April 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29341143/loss-of-alkaline-ceramidase-inhibits-autophagy-in-arabidopsis-and-plays-an-important-role-during-environmental-stress-response
#19
Ping Zheng, Jian-Xin Wu, Sunil Kumar Sahu, Hong-Yun Zeng, Li-Qun Huang, Zhe Liu, Shi Xiao, Nan Yao
Sphingolipids, a class of bioactive lipids found in cell membranes, can modulate the biophysical properties of the membranes and play a critical role in signal transduction. Sphingolipids are involved in autophagy in humans and yeast, but their role in autophagy in plants is not well understood. In this study, we reported that the AtACER, an alkaline ceramidase that hydrolyzes ceramide to LCB, functions in autophagy process in Arabidopsis. Our empirical data showed that the loss of AtACER inhibited autophagy, while its overexpression promoted autophagy under nutrient, salinity, and oxidative stresses...
January 17, 2018: Plant, Cell & Environment
https://www.readbyqxmd.com/read/29331057/manifestations-and-mechanisms-of-myocardial-lipotoxicity-in-obesity
#20
A C Sletten, L R Peterson, J E Schaffer
Environmental and socioeconomic changes over the past thirty years have contributed to a dramatic rise in the worldwide prevalence of obesity. Heart disease is amongst the most serious health risks of obesity, with increases in both atherosclerotic coronary heart disease and heart failure among obese individuals. In this review, we focus on primary myocardial alterations in obesity that include hypertrophic remodelling and diastolic dysfunction. Obesity-associated perturbations in myocardial and systemic lipid metabolism are important contributors to cardiovascular complications of obesity...
January 13, 2018: Journal of Internal Medicine
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