Lipids Commons^™

Dynamic Cycling Of T-Snare Acylation Regulates Platelet Exocytosis, Jinchao Zhang, Yunjie Huang, Jing Chen, Haining Zhu, Sidney W. Whiteheart

Molecular and Cellular Biochemistry Faculty Publications

Platelets regulate vascular integrity by secreting a host of molecules that promote hemostasis and its sequelae. Given the importance of platelet exocytosis, it is critical to understand how it is controlled. The t-SNAREs, SNAP-23 and syntaxin-11, lack classical transmembrane domains (TMDs), yet both are associated with platelet membranes and redistributed into cholesterol-dependent lipid rafts when platelets are activated. Using metabolic labeling and hydroxylamine (HA)/HCl treatment, we showed that both contain thioester-linked acyl groups. Mass spectrometry mapping further showed that syntaxin-11 was modified on cysteine 275, 279, 280, 282, 283, and 285, and SNAP-23 was modified on cysteine 79, 80, 83, …

Novel Function Of Ceramide For Regulation Of Mitochondrial Atp Release In Astrocytes, Ji-Na Kong, Zhihui Zhu, Yutaka Itokazu, Guanghu Wang, Michael B. Dinkins, Liansheng Zhong, Hsuan-Pei Lin, Ahmed Elsherbini, Silvia Leanhart, Xue Jiang, Haiyan Qin, Wenbo Zhi, Stefka D. Spassieva, Erhard Bieberich

Physiology Faculty Publications

We reported that amyloid β peptide (Aβ₄₂) activated neutral SMase 2 (nSMase2), thereby increasing the concentration of the sphingolipid ceramide in astrocytes. Here, we show that Aβ₄₂ induced mitochondrial fragmentation in wild-type astrocytes, but not in nSMase2-deficient cells or astrocytes treated with fumonisin B1 (FB1), an inhibitor of ceramide synthases. Unexpectedly, ceramide depletion was concurrent with rapid movements of mitochondria, indicating an unknown function of ceramide for mitochondria. Using immunocytochemistry and super-resolution microscopy, we detected ceramide-enriched and mitochondria-associated membranes (CEMAMs) that were codistributed with microtubules. Interaction of ceramide with tubulin was confirmed by cross-linking to N-[9-(3-pent-4-ynyl-3-H-diazirine-3-yl)-nonanoyl]-D-erythro-sphingosine …

Naturally Occurring 3rs, 7r, 11r-Phytanic Acid Suppresses In Vitro T-Cell Production Of Interferon-Gamma, Tomonori Nakanishi, Ibuki Motoba, Mayuko Anraku, Ryoji Suzuki, Yuto Yamaguchi, Laurie Erickson, Satoshi Kawahara

Hebrew Theological College Publications and Research

Background: Among the eight stereoisomers of phytanic acid (PA), the 3RS, 7R, 11R-isomer is naturally occurring and is present in foods and the human body. PA is considered to have possible health benefits in the immune system. However, it remains undetermined whether these effects are elicited by the 3RS, 7R, 11R-PA isomer, because previous studies used a commercially available PA whose isomer configuration is unknown. In this study, we synthesized a preparation of 3RS, 7R, 11R-PA, and investigated its in vitro immunomodulatory effects, especially the T-cell production of interferon (IFN)-γ, which is associated with various autoimmune diseases. This study …

The Role Of Ceramide In Neutrophil Elastase Induced Inflammation In The Lungs, Sophia Karandashova

Theses and Dissertations

Alterations to sphingolipid metabolism are associated with increased pulmonary inflammation, but the impact of inflammatory mediators, such as neutrophil elastase (NE), on airway sphingolipid homeostasis remains unknown. NE is a protease associated CF lung disease progression, and can be found in up to micromolar concentrations in patient airways. While sphingolipids have been investigated in the context of CF, the focus has been on loss of cystic fibrosis transmembrane conductance regulator (CFTR) function. Here, we present a novel observation: oropharyngeal aspiration of NE increases airway ceramides in mice. Using a previously characterized mouse model of NE-induced inflammation, we demonstrate that NE …

The Forensic Characterization Of Bacterial And Fungal Organisms In Traditional Chinese Medicine, Julia Grzymkowski, Christopher J. Ehrhardt, Justin L. Poklis, Michelle R. Peace

Undergraduate Research Posters

There has been an increase in use of Traditional Chinese Medicine (TCM) in the United States because they are less expensive and believed to be more effective with less adverse effects in comparison to traditional pharmaceutics. Therefore, sales have increased in the US, despite articles and case studies demonstrating the dangers, such as injury and death, related to TCM, stemming from improper labelling, toxic contaminants, and, in some cases, the presence of pathogenic bacteria. The aim of this study was to perform a survival experiment to demonstrate the importance of proper herbal brewing technique and to conduct a molecular and …

Pde8 Is Expressed In Human Airway Smooth Muscle And Selectively Regulates Camp Signaling By Β 2 Ar-Ac6, Timothy B. Johnstone, Kaitlyn H. Smith, Cynthia J. Koziol-White, Fengying Li, Austin G. Kazarian, Maia L. Corpuz, Maya Shumyachter, Frederick J. Ehlert, Bianca E. Himes, Reynold A. Pannettieri Jr., Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

Two cAMP signaling compartments centering around adenylyl cyclase (AC) exist in human airway smooth muscle (HASM) cells, one containing ß2AR-AC6 and another containing E prostanoid receptors (EPR)-AC2. We hypothesized that different phosphodiesterase (PDE) isozymes selectively regulate cAMP signaling in each compartment. According to RNA-seq data, 18 of 24 PDE genes were expressed in primary HASM cells derived from age- and gender-matched donors with and without asthma. PDE8A was the third most abundant of the cAMP-degrading PDE genes, after PDE4A and PDE1A. Knockdown of PDE8A using shRNA evoked 2-fold greater cAMP responses to 1 DM forskolin in the presence of IBMX. …

Modification Of The Ribosome As Part Of The Adaptive Response To Oxidative Stress In Yeast, Jessica A Zinskie, Daniel Shedlovskiy, Ethan Gardner, Dimitri G Pestov, Natalia Shcherbik

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Living organisms are constantly exposed to a variety of environmental and internal stressors tha tare detrimental to their cellular physiology and viability. One such condition, oxidativestress, is caused by abnormal amounts of Reactive Oxygen Species (ROS) that can lead to damage to proteins, nucleic acids, and lipids. Although the mechanisms to neutralize ROS have been widely studied, the understanding of ROS‐mediated signaling for these mechanisms is rather incomplete and sparse. We have uncovered a previously undescribed phenomenon of yeast ribosomes to respond to elevated levels of ROS through a specific endonucleolytic cleavage of the 25S rRNA in the c‐loop of …

Serum Amyloid A3 Is A High Density Lipoprotein-Associated Acute-Phase Protein, Lisa R. Tannock, Maria C. De Beer, Ailing Ji, Preetha Shridas, Victoria P. Noffsinger, Laura Den Hartigh, Alan Chait, Frederick C. De Beer, Nancy R. Webb

Internal Medicine Faculty Publications

Serum amyloid A (SAA) is a family of acute-phase reactants. Plasma levels of human SAA1/SAA2 (mouse SAA1.1/2.1) can increase ≥ 1,000-fold during an acute-phase response. Mice, but not humans, express a third relatively understudied SAA isoform, SAA3. We investigated whether mouse SAA3 is an HDL-associated acute-phase SAA. Quantitative RT-PCR with isoform-specific primers indicated that SAA3 and SAA1.1/2.1 are induced similarly in livers (∼2,500-fold vs. ∼6,000-fold, respectively) and fat (∼400-fold vs. ∼100-fold, respectively) of lipopolysaccharide (LPS)-injected mice. In situ hybridization demonstrated that all three SAAs are produced by hepatocytes. All three SAA isoforms were detected in plasma of LPS-injected mice, although …

Prevention Of Renal Apob Retention Is Protective Against Diabetic Nephropathy: Role Of Tgf-Β Inhibition, Patricia G. Wilson, Joel C. Thompson, Meghan S. Yoder, Richard Charnigo, Lisa R. Tannock

Internal Medicine Faculty Publications

Animal studies demonstrate that hyperlipidemia and renal lipid accumulation contribute to the pathogenesis of diabetic nephropathy (DN). We previously demonstrated that renal lipoproteins colocalize with biglycan, a renal proteoglycan. The purpose of this study was to determine whether prevention of renal lipid (apoB) accumulation attenuates DN. Biglycan-deficient and biglycan wild-type Ldlr^−/− mice were made diabetic via streptozotocin and fed a high cholesterol diet. As biglycan deficiency is associated with elevated transforming growth factor-β (TGF-β), in some experiments mice were injected with either the TGF-β-neutralizing antibody, 1D11, or with 13C4, an irrelevant control antibody. Biglycan deficiency had no significant effect …

Roles Of Gabab, Muscarinic And Nicotinic Receptor Signaling In The Acquisition And Expression Of Fructose And Fat-Conditioned Flavor Preferences And Acquisition Of Quinine-Conditioned Flavor Avoidances In Rats, Francis M. Rotella

Dissertations, Theses, and Capstone Projects

In addition to increased intake of sweet solutions by mammals, learning, particularly classically-conditioned “Pavlovian-like” learning, also plays an important role. An orosensory conditioned flavor preference (CFP) can be elicited by pairing one novel flavor (conditioned stimulus, CS+) with a fructose solution and a second novel flavor (CS-) with a saccharin solution. Rats will prefer the CS+ flavor in a subsequent 2-bottle choice test with both flavors mixed in saccharin. Previous pharmacological analyses revealed that systemic administration of dopamine (DA) D1 and D2 as well as NMDA, but not opioid, receptor antagonists eliminated the acquisition (learning) of fructose-CFP. Further, expression of …

Naturally-Derived Molecular Ensembles In Medicine, Materials Science And Evolutionary Biology: An Interdisciplinary Study, Silvio Panettieri

Dissertations, Theses, and Capstone Projects

The first chapter will introduce the work carried out in collaboration with the Govind laboratory at CCNY. Our quest was set forth to investigate the intimate relationship lying between chronic inflammation and tumor development. For at least the last fifteen years much research has been conducted on this topic; yet, the level of complexity arising from exceedingly interwoven biochemical pathways in mammals has resulted in slow advancements in this field. This is why we resorted to a simple yet powerful immunogenetic model organism, the fruit fly Drosophila melanogaster, in combination with the administration of the most common anti-inflammatory drug, …

Diversity Oriented Synthesis, Characterization And Anti-Cancer Activity Of Killer Peptide Nucleolipid Bioconjugates, Niki K. Rana

Seton Hall University Dissertations and Theses (ETDs)

The killer peptide sequence D-(KLAKLAK)₂ has been originally designed and developed as an antibacterial agent. Despite having excellent cytotoxicity towards bacteria, this sequence maintains low cell cytotoxity in malignant mammalian cell types such as cancer. The chemical basis for its selectivity has been attributed to its poly(cationic) amphiphilic nature, which facilitates cell permeability across the negatively charged bacterial membrane, but with limited permeability across the zwitterionic membrane of mammalian cells. The positively charged D-(KLAKLAK)₂ sequence has been found to accumulate on the surface of the mitochondria causing dissipation of the negatively charged mitochondrial membrane potential. This charge disruption …

Role Of Inflammation In 20-Hete Regulation Of Ischemia-Induced Angiogenesis, Elizabeth Berry, Rachel John, Samantha Tang, Austin M. Guo

NYMC Faculty Posters

Objective: 20-Hydroxyeicosatetraenoic acid (20-HETE), an important bioactive lipid metabolite, has recently been identified to be a novel contributor of angiogenesis secondary to ischemia. Moreover, an inflammatory response is required for the initiation of ischemic angiogenesis, in response to ischemic tissue injury. The goal of this study is to investigate the role of inflammation in 20-HETE regulation of ischemia-induced angiogenesis.

Methods: We first established a mouse hind limb ischemia model for immunocompetent Balb/C mice and immunodeficient NOD-SCID mice by femoral artery ligation. Groups of Balb/C and NOD-SCID mice were administered a 20-HETE synthesis inhibitor, DDMS, or saline as a solvent control. …

Discovering A Novel Antifungal Target In Downstream Sterol Biosynthesis Using A Squalene Synthase Functional Motif, Kristin Brooke Linscott

Theses and Dissertations--Molecular and Cellular Biochemistry

The sterol biosynthetic pathway is essential for growth of all eukaryotic cells and the main target of antifungal agents. The emergence of resistance to these antifungals in an already ill patient population indicates a need to develop drugs that have a broad spectrum of activity among pathogenic fungi and have minimal patient toxicity. Squalene synthase is the first committed step in the sterol pathway and has been studied intensively for development of antifungal agents. While the overall architecture of this enzyme is identical throughout eukaryotes, it was shown that plant and animal genes cannot complement a squalene synthase knockout mutation …

Similar Adverse Events From Two Disparate Agents Implicate Lipid Inflammatory Mediators For A Role In Anxiety States, Gordon Mccarter, Lauren B. Blanchard

Faculty Publications & Research of the TUC College of Pharmacy

We recently reported a case in which a 54-year-old male experienced maintenance insomnia, generalized anxiety and panic symptoms associated with consumption of a fish oil supplement enriched in eicosapentaenoic acid (EPA). We report here that the same patient has experienced identical but more severe symptoms in response to the use of the leukotriene receptor antagonist montelukast, in accordance with other cases reported to the Food and Drug Administration. Since omega-3 fatty acids like EPA are precursors for the biosynthesis of eicosanoids including leukotrienes, a common factor to these psychiatric adverse events may be perturbations in this highly complex system of …

Lack Of Cross-Reactivity Allergy Following A Switch From Alirocumab To Evolocumab, Matthew D. Stryker, Michael Kane, Robert Busch

Excerpts in Pharmacy Research Journal

The proprotein convertase subtilisin/kexin type 9 (PCSK9) gene and gain-of-function mutations were first described in 2003. The gain-of-function mutations observed were associated with low-density lipoprotein-cholesterol (LDL-C) levels in the 400’s, in addition to premature cardiovascular disease. Subsequent loss-of-function experiments conducted in mice demonstrated marked reductions in plasma cholesterol levels in the absence of PCSK9. Physiologically, PCSK9 serves as a chaperone protein and functions to reduce low-density lipoprotein (LDL) receptor recycling; consequently, less LDL-C is removed from circulation and serum lipid concentrations become elevated. Inhibition of PCSK9 prevents LDL receptor degradation and preserves receptor recycling to the hepatocyte surface; this in …

Epigenetics Of Lipid Phenotypes, Sergi Sayols-Baixeras, Marguerite R. Irvin, Donna K. Arnett, Roberto Elosua, Stella W. Aslibekyan

Epidemiology and Environmental Health Faculty Publications

Dyslipidemia is a well-established risk factor for cardiovascular disease, the main cause of death worldwide. Blood lipid profiles are patterned by both genetic and environmental factors. In recent years, epigenetics has emerged as a paradigm that unifies these influences. In this review, we have summarized the latest evidence implicating epigenetic mechanisms—DNA methylation, histone modification, and regulation by RNAs—in lipid homeostasis. Key findings have emerged in a number of novel epigenetic loci located in biologically plausible genes (eg, CPT1A, ABCG1, SREBF1, and others), as well as microRNA-33a/b. Evidence from animal and cell culture models suggests a complex interplay …

The Impact Of Polybrominated Diphenyl Ether (Bde-47) Administration In Mice And Its Implications In Non-Alcoholic Fatty Liver Disease, Kristen Ciampi

Senior Honors Projects

Non-alcoholic fatty liver disease (NAFLD) is a disease characterized by the accumulation of fat in liver cells that is not due to alcohol consumption. Steatosis results when more than 5-10% of the liver’s weight consists of fat. People who are overweight, or who have diabetes or high cholesterol are more likely to develop NAFLD. Over time, NAFLD can advance to cause cirrhosis, and eventually, liver cancer or failure.

Polybrominated diphenyl ethers (PBDEs, BDEs) are brominated flame- retardants, and are found in many plastics and household products such as cars, textiles, televisions, and computers. BDEs are released into the environment and …

Micellular Electrokinetic Chromatography For Studying Amyloid Beta Oligomer Membrane Affinity, Andrew Bryson

Biomedical Engineering Undergraduate Honors Theses

Amyloid Beta (Aβ) was the major focus of this study. It is a peptide that is present in the brain with a high tendency to self-aggregate. When this protein aggregates, it forms oligomers and protofibrils which in turn are deposited as senile plaques in the brain. The reason for the concern with these plaques is their association with the neurological disorder Alzheimer’s disease. It has been found that the most dangerous oligomers are formed in a portion of the plasma membrane known as lipid rafts. The purpose of this study was to understand how micelles affect the aggregation properties of …

Anti-Cancer Diets: Revolution Or Ruse?, Lauren Hogan

First Year Inquiry: Student Scholarship & Creative Works

This paper discusses how the foods we consume can play a role in the diagnosis of cancer.