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Full-Text Articles in Medicine and Health Sciences
Observing Ceramide Pathway With Ferroptosis Via Mia Paca-2 Cell Treatment With Rsl3, Tazrin Rahman
Observing Ceramide Pathway With Ferroptosis Via Mia Paca-2 Cell Treatment With Rsl3, Tazrin Rahman
AUCTUS: The Journal of Undergraduate Research and Creative Scholarship
Composed of sphingosine and a fatty acid, ceramides are lipid molecules that serve as key metabolic signaling molecules of a sphingolipid pathway. While it acts as a precursor of complex sphingolipids, inducing ceramide generation can cause cell stress leading to subsequent cell death via apoptosis, necrosis, and even mitophagy. With regards to cell death specifically, a novel form of regulated cell death, ferroptosis, has recently been recognized of necrotic nature. Its unique morphological features and distinct properties have been observed over the last several decades; however, the molecular features were not identifiable as pure evidence of cell death, until recently …
Increased Liver Tumor Formation In Neutral Sphingomyelinase-2-Deficient Mice, Liansheng Zhong, Ji Na Kong, Michael B. Dinkins, Silvia Leanhart, Zhihui Zhu, Stefka D. Spassieva, Haiyan Qin, Hsuan-Pei Lin, Ahmed Elsherbini, Rebecca Wang, Xue Jiang, Mariana N. Nikolova‑Karakashian, Guanghu Wang, Erhard Bieberich
Increased Liver Tumor Formation In Neutral Sphingomyelinase-2-Deficient Mice, Liansheng Zhong, Ji Na Kong, Michael B. Dinkins, Silvia Leanhart, Zhihui Zhu, Stefka D. Spassieva, Haiyan Qin, Hsuan-Pei Lin, Ahmed Elsherbini, Rebecca Wang, Xue Jiang, Mariana N. Nikolova‑Karakashian, Guanghu Wang, Erhard Bieberich
Physiology Faculty Publications
Sphingolipids are key signaling lipids in cancer. Genome-wide studies have identified neutral SMase-2 (nSMase2), an enzyme generating ceramide from SM, as a potential repressor for hepatocellular carcinoma. However, little is known about the sphingolipids regulated by nSMase2 and their roles in liver tumor development. We discovered growth of spontaneous liver tumors in 27.3% (9 of 33) of aged male nSMase2-deficient (fro/fro) mice. Lipidomics analysis showed a marked increase of SM in the tumor. Unexpectedly, tumor tissues presented with more than a 7-fold increase of C16-ceramide, concurrent with upregulation of ceramide synthase 5. The fro/fro liver tumor, …
Sphingolipids In Models Of Kidney Disease And Injury., Tess V. Dupre
Sphingolipids In Models Of Kidney Disease And Injury., Tess V. Dupre
Electronic Theses and Dissertations
Acute kidney injury (AKI), resulting from cisplatin, remains an obstacle in the treatment of cancer. Cisplatin-induced AKI involves cell death pathways regulated by sphingolipids such as ceramide and glucosylceramide. Results indicate that cisplatin-treated mice had increased levels of ceramide and hexosylceramide. Pre-treatment of mice with inhibitors of ceramide synthesis prevented accumulation of ceramide and hexosylceramide in the renal cortex and attenuated cisplatin-induced AKI. To determine the role of ceramide metabolism to hexosylceramides in kidney injury, we treated mice with an inhibitor of glycosphingolipid synthesis. Inhibition of glycosphingolipid synthesis attenuated the accumulation of the hexosylceramide and exacerbated ceramide accumulation in the …
Novel Interconnections In Lipid Metabolism Revealed By Overexpression Of Sphingomyelin Synthase-1, Gergana M. Deevska, Patrick P. Dotson Ii, Alexander A. Karakashian, Giorgis Isaac, Mark Wrona, Samuel B. Kelly, Alfred H. Merrill Jr., Mariana N. Nikolova‑Karakashian
Novel Interconnections In Lipid Metabolism Revealed By Overexpression Of Sphingomyelin Synthase-1, Gergana M. Deevska, Patrick P. Dotson Ii, Alexander A. Karakashian, Giorgis Isaac, Mark Wrona, Samuel B. Kelly, Alfred H. Merrill Jr., Mariana N. Nikolova‑Karakashian
Physiology Faculty Publications
This study investigates the consequences of elevating sphingomyelin synthase 1 (SMS1) activity, which generates the main mammalian sphingolipid, sphingomyelin. HepG2 cells stably transfected with SMS1 (HepG2-SMS1) exhibit elevated enzyme activity in vitro and increased sphingomyelin content (mainly C22:0- and C24:0-sphingomyelin) but lower hexosylceramide (Hex-Cer) levels. HepG2-SMS1 cells have fewer triacylglycerols than controls but similar diacylglycerol acyltransferase activity, triacylglycerol secretion, and mitochondrial function. Treatment with 1 mm palmitate increases de novo ceramide synthesis in both cell lines to a similar degree, causing accumulation of C16:0-ceramide (and some C18:0-, C20:0-, and C22:0-ceramides) as well as C16:0- and C18:0-Hex-Cers. In these experiments, the …
Efficacy Of Nutritional Interventions To Lower Circulating Ceramides In Young Adults: Fruvedomic Pilot Study, Alice T. Matthews, Oluremi A. Famodu, Melissa D. Olfert, Pamela J. Murray, Christopher F. Cuff, Marianne T. Downes, Norman J. Haughey, Sarah E. Colby, Paul D. Chantler, I. Mark Olfert, Joseph W. Mcfadden
Efficacy Of Nutritional Interventions To Lower Circulating Ceramides In Young Adults: Fruvedomic Pilot Study, Alice T. Matthews, Oluremi A. Famodu, Melissa D. Olfert, Pamela J. Murray, Christopher F. Cuff, Marianne T. Downes, Norman J. Haughey, Sarah E. Colby, Paul D. Chantler, I. Mark Olfert, Joseph W. Mcfadden
Faculty & Staff Scholarship
The 2010 USDA Dietary Guidelines for Americans (DGA) recommends a diet largely composed of fruit and vegetables. Consuming a diet high in fruit and vegetables and low in refined carbohydrates and saturated fat may reduce an individual’s risk for type 2 diabetes, nonalcoholic fatty liver disease, low-grade chronic inflammation, and metabolic syndrome (MetS). Several recent studies have implicated the bioactive sphingolipid ceramide as an associative and causative biomarker for the development of these conditions. Considering that the intake of fruit and vegetables is frequently inadequate in young adults, we performed a pilot investigation to assess the efficacy of a free-living …
Genotoxic Effects Of Magnesium Deficiency In The Cardiovascular System And Their Relationships To Cardiovascular Diseases And Atherogenesis, Burton M. Altura, Nilank C. Shah, Gatha J. Shah, Bella T. Altura
Genotoxic Effects Of Magnesium Deficiency In The Cardiovascular System And Their Relationships To Cardiovascular Diseases And Atherogenesis, Burton M. Altura, Nilank C. Shah, Gatha J. Shah, Bella T. Altura
The School of Health Sciences Publications and Research
The authors present evidence for a novel, new hypothesis whereby magnesium deficiency (MgD) acts as a genotoxic agent which probably causes numerous, hertofore, unrecognized consequences, even over a short-term, on the physiological, molecular and biochemical machinery of cardiovascular tissues and cells. The end result of these genotoxic effects of MgD probably plays important roles in the etiology and generation of diverse cardiovascular diseases, atherosclerosis, inflammation, and strokes via alterations in the epigenome of cardiovascular tissues and cells. The importance of adequate water-borne and dietary levels of Mg is emphasized.
Magnesium Deficiency Results In Oxidation And Fragmentation Of Dna, Down Regulation Of Telomerase Activity, And Ceramide Release In Cardiovascular Tissues And Cells: Potential Relationship To Atherogenesis, Cardiovascular Diseases And Aging, Burton M. Altura, Nilank C. Shah, Gatha J. Shah, Jose Luis Perez-Albela, Bella T. Altura
Magnesium Deficiency Results In Oxidation And Fragmentation Of Dna, Down Regulation Of Telomerase Activity, And Ceramide Release In Cardiovascular Tissues And Cells: Potential Relationship To Atherogenesis, Cardiovascular Diseases And Aging, Burton M. Altura, Nilank C. Shah, Gatha J. Shah, Jose Luis Perez-Albela, Bella T. Altura
The School of Health Sciences Publications and Research
The authors discuss the potential relationship between magnesium, cardiovascular diseases, and aging.
Insights Into The Possible Mechanisms By Which Platelet-Activating Factor And Paf-Receptors Function In Vascular Smooth Muscle In Magnesium Deficiency And Vascular Remodeling: Possible Links To Atherogenesis, Hypertension And Cardiac Failure, Burton M. Altura, Nilank C. Shah, Gatha J. Shah, Jose Luis Perez-Albela, Bella T. Altura
Insights Into The Possible Mechanisms By Which Platelet-Activating Factor And Paf-Receptors Function In Vascular Smooth Muscle In Magnesium Deficiency And Vascular Remodeling: Possible Links To Atherogenesis, Hypertension And Cardiac Failure, Burton M. Altura, Nilank C. Shah, Gatha J. Shah, Jose Luis Perez-Albela, Bella T. Altura
The School of Health Sciences Publications and Research
The authors discuss different studies concerning the relationship between platelet-activating factor (PAF) and PAF-receptors with atherosclerosis and hypertension.
The Role Of Sirtuin 1 And Ceramide In T10C12 Conjugated Linoleic Acid Induced Delipidation In 3t3-L1 Adipocytes, Wei Wang
Department of Animal Science: Dissertations, Theses, and Student Research
Project 1: Trans-10, cis-12 conjugated linoleic acid (t10c12 CLA) reduces triglyceride (TG) levels in adipocytes through multiple pathways, with AMP-activated protein kinase (AMPK) generally facilitating, and peroxisome proliferator-activated receptor γ (PPARγ) generally opposing these reductions. Sirtuin 1 (SIRT1), a histone/protein deacetylase that affects energy homeostasis, often functions coordinately with AMPK, and is capable of binding to PPARγ, thereby inhibiting its activity. This study investigated the role of SIRT1 in the response of 3T3-L1 adipocytes to t10c12 CLA by testing the following hypotheses: 1) SIRT1 is functionally required for robust TG reduction; …
Characterization Of Secretory Sphingomyelinase Activity, Lipoprotein Sphingolipid Content And Ldl Aggregation In Ldlr-/- Mice Fed On A High-Fat Diet, Gergana M. Deevska, Manjula Sunkara, Andrew J. Morris, Mariana N. Nikolova‑Karakashian
Characterization Of Secretory Sphingomyelinase Activity, Lipoprotein Sphingolipid Content And Ldl Aggregation In Ldlr-/- Mice Fed On A High-Fat Diet, Gergana M. Deevska, Manjula Sunkara, Andrew J. Morris, Mariana N. Nikolova‑Karakashian
Physiology Faculty Publications
The propensity of LDLs (low-density lipoproteins) for aggregation and/or oxidation has been linked to their sphingolipid content, specifically the levels of SM (sphingomyelin) and ceramide. To investigate this association in vivo, ldlr (LDL receptor)-null mice (ldlr-/-) were fed on a modified (atherogenic) diet containing saturated fats and cholesterol. The diet led to significantly elevated SM content in all serum lipoproteins. In contrast, ceramide increased only in the LDL particles. MS-based analyses of the lipid acyl chain composition revealed a marked elevation in C16:0 fatty acid in SM and ceramide, consistent with the prevalence of palmitic acid in the modified diet. …
Saturated- And N-6 Polyunsaturated-Fat Diets Each Induce Ceramide Accumulation In Mouse Skeletal Muscle: Reversal And Improvement Of Glucose Tolerance By Lipid Metabolism Inhibitors, G Frangioudakis, J Garrard, K Raddatz, J L. Nadler, Todd W. Mitchell, Carsten Schmitz-Peiffer
Saturated- And N-6 Polyunsaturated-Fat Diets Each Induce Ceramide Accumulation In Mouse Skeletal Muscle: Reversal And Improvement Of Glucose Tolerance By Lipid Metabolism Inhibitors, G Frangioudakis, J Garrard, K Raddatz, J L. Nadler, Todd W. Mitchell, Carsten Schmitz-Peiffer
Faculty of Health and Behavioural Sciences - Papers (Archive)
Lipid-induced insulin resistance is associated with intracellular accumulation of inhibitory intermediates depending on the prevalent fatty acid (FA) species. In cultured myotubes, ceramide and phosphatidic acid (PA) mediate the effects of the saturated FA palmitate and the unsaturated FA linoleate, respectively. We hypothesized that myriocin (MYR), an inhibitor of de novo ceramide synthesis, would protect against glucose intolerance in saturated fat-fed mice, while lisofylline (LSF), a functional inhibitor of PA synthesis, would protect unsaturated fat-fed mice. Mice were fed diets enriched in saturated fat, n-6 polyunsaturated fat, or chow for 6 wk. Saline, LSF (25 mg/kg · d), or MYR …