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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Comparison Of Rna Isolation And Associated Methods For Extracellular Rna Detection By High-Throughput Quantitative Polymerase Chain Reaction, Kahraman Tanriverdi, Alper Kucukural, Ekaterina Mikhalev, Selim E. Tanriverdi, Rosalind Lee, Victor R. Ambros, Jane Freedman Apr 2016

Comparison Of Rna Isolation And Associated Methods For Extracellular Rna Detection By High-Throughput Quantitative Polymerase Chain Reaction, Kahraman Tanriverdi, Alper Kucukural, Ekaterina Mikhalev, Selim E. Tanriverdi, Rosalind Lee, Victor R. Ambros, Jane Freedman

Victor R. Ambros

MicroRNAs (miRNAs) are small noncoding RNA molecules that function in RNA silencing and posttranscriptional regulation of gene expression. miRNAs in biofluids are being used for clinical diagnosis as well as disease prediction. Efficient and reproducible isolation methods are crucial for extracellular RNA detection. To determine the best methodologies for miRNA detection from plasma, the performance of four RNA extraction kits, including an in-house kit, were determined with miScript miRNA assay technology; all were measured using a high-throughput quantitative polymerase chain reaction (qPCR) platform (BioMark System) with 90 human miRNA assays. In addition, the performances of complementary DNA (cDNA) and preamplification ...


Genetic And Acute Cpeb1 Depletion Ameliorate Fragile X Pathophysiology, Tsuyoshi Udagawa, Natalie Farny, Mira Jakovcevski, Hanoch Kaphzan, Juan Alarcon, Shobha Anilkumar, Maria Ivshina, Jessica Hurt, Kentaro Nagaoka, Vijayalaxmi Nalavadi, Lori Lorenz, Gary Bassell, Schahram Akbarian, Sumantra Chattarji, Eric Klann, Joel Richter Dec 2015

Genetic And Acute Cpeb1 Depletion Ameliorate Fragile X Pathophysiology, Tsuyoshi Udagawa, Natalie Farny, Mira Jakovcevski, Hanoch Kaphzan, Juan Alarcon, Shobha Anilkumar, Maria Ivshina, Jessica Hurt, Kentaro Nagaoka, Vijayalaxmi Nalavadi, Lori Lorenz, Gary Bassell, Schahram Akbarian, Sumantra Chattarji, Eric Klann, Joel Richter

Natalie G. Farny

Fragile X syndrome (FXS), the most common cause of inherited mental retardation and autism, is caused by transcriptional silencing of FMR1, which encodes the translational repressor fragile X mental retardation protein (FMRP). FMRP and cytoplasmic polyadenylation element-binding protein (CPEB), an activator of translation, are present in neuronal dendrites, are predicted to bind many of the same mRNAs and may mediate a translational homeostasis that, when imbalanced, results in FXS. Consistent with this possibility, Fmr1(-/y); Cpeb1(-/-) double-knockout mice displayed amelioration of biochemical, morphological, electrophysiological and behavioral phenotypes associated with FXS. Acute depletion of CPEB1 in the hippocampus of adult Fmr1 ...


Characterization And Structure Of A Zn2+ And [2fe-2s]-Containing Copper Chaperone From Archaeoglobus Fulgidus, Matthew Sazinsky, Benjamin Lemoine, Maria Orofino, Roman Davydov, Krisztina Bencze, Timothy Stemmler, Brian Hoffman, José Argüello, Amy Rosenzweig Dec 2015

Characterization And Structure Of A Zn2+ And [2fe-2s]-Containing Copper Chaperone From Archaeoglobus Fulgidus, Matthew Sazinsky, Benjamin Lemoine, Maria Orofino, Roman Davydov, Krisztina Bencze, Timothy Stemmler, Brian Hoffman, José Argüello, Amy Rosenzweig

José M. Argüello

Bacterial CopZ proteins deliver copper to P1B-type Cu+-ATPases that are homologous to the human Wilson and Menkes disease proteins. The genome of the hyperthermophile Archaeoglobus fulgidus encodes a putative CopZ copper chaperone that contains an unusual cysteine rich N-terminal domain of 130 amino acids in addition to a C-terminal copper-binding domain with a conserved CXXC motif. The N-terminal domain (CopZ-NT) is homologous to proteins found only in extremophiles and is the only such protein that is fused to a copper chaperone. Surprisingly, optical, electron paramagnetic resonance, and X-ray absorption spectroscopic data indicate the presence of a [2Fe-2S] cluster in ...


Correlations Between Oxygen Affinity And Sequence Classifications Of Plant Hemoglobins, Benoit Smagghe, Julie Hoy, Ryan Percifield, Suman Kundu, Mark Hargrove, Gautam Sarath, Jean-Louis Hilbert, Richard Watts, Elizabeth Dennis, W. James Peacock, Sylvia Dewilde, Luc Moens, George Blouin, John Olson, Cyril Appleby Dec 2015

Correlations Between Oxygen Affinity And Sequence Classifications Of Plant Hemoglobins, Benoit Smagghe, Julie Hoy, Ryan Percifield, Suman Kundu, Mark Hargrove, Gautam Sarath, Jean-Louis Hilbert, Richard Watts, Elizabeth Dennis, W. James Peacock, Sylvia Dewilde, Luc Moens, George Blouin, John Olson, Cyril Appleby

John Olson

Plants express three phylogenetic classes of hemoglobins (Hb) based on sequence analyses. Class 1 and 2 Hbs are full-length globins with the classical eight helix Mb-like fold, whereas Class 3 plant Hbs resemble the truncated globins found in bacteria. With the exception of the specialized leghemoglobins, the physiological functions of these plant hemoglobins remain unknown. We have reviewed and, in some cases, measured new oxygen binding properties of a large number of Class 1 and 2 plant nonsymbiotic Hbs and leghemoglobins. We found that sequence classification correlates with distinct extents of hexacoordination with the distal histidine and markedly different overall ...


Cytoplasmic Ph Measurement And Homeostasis In Bacteria And Archaea., Joan Slonczewski Nov 2015

Cytoplasmic Ph Measurement And Homeostasis In Bacteria And Archaea., Joan Slonczewski

Joan Slonczewski

Of all the molecular determinants for growth, the hydronium and hydroxide ions are found naturally in the widest concentration range, from acid mine drainage below pH 0 to soda lakes above pH 13. Most bacteria and archaea have mechanisms that maintain their internal, cytoplasmic pH within a narrower range than the pH outside the cell, termed "pH homeostasis." Some mechanisms of pH homeostasis are specific to particular species or groups of microorganisms while some common principles apply across the pH spectrum. The measurement of internal pH of microbes presents challenges, which are addressed by a range of techniques under varying ...


Rna Recognition By The Caenorhabditis Elegans Oocyte Maturation Determinant Oma-1, Ebru Kaymak, Sean Ryder Oct 2015

Rna Recognition By The Caenorhabditis Elegans Oocyte Maturation Determinant Oma-1, Ebru Kaymak, Sean Ryder

Sean P. Ryder

Maternally supplied mRNAs encode proteins that pattern early embryos in many species. In the nematode Caenorhabditis elegans, a suite of RNA-binding proteins regulates expression of maternal mRNAs during oogenesis, the oocyte to embryo transition, and early embryogenesis. To understand how these RNA-binding proteins contribute to development, it is necessary to determine how they select specific mRNA targets for regulation. OMA-1 and OMA-2 are redundant proteins required for oocyte maturation--an essential part of meiosis that prepares oocytes for fertilization. Both proteins have CCCH type tandem zinc finger RNA-binding domains. Here, we define the RNA binding specificity of OMA-1 and demonstrate that ...


Control Of Stem Cell Self-Renewal And Differentiation By The Heterochronic Genes And The Cellular Asymmetry Machinery In Caenorhabditis Elegans, Omid F. Harandi, Victor Ambros Oct 2015

Control Of Stem Cell Self-Renewal And Differentiation By The Heterochronic Genes And The Cellular Asymmetry Machinery In Caenorhabditis Elegans, Omid F. Harandi, Victor Ambros

Victor R. Ambros

Transitions between asymmetric (self-renewing) and symmetric (proliferative) cell divisions are robustly regulated in the context of normal development and tissue homeostasis. To genetically assess the regulation of these transitions, we used the postembryonic epithelial stem (seam) cell lineages of Caenorhabditis elegans. In these lineages, the timing of these transitions is regulated by the evolutionarily conserved heterochronic pathway, whereas cell division asymmetry is conferred by a pathway consisting of Wnt (Wingless) pathway components, including posterior pharynx defect (POP-1)/TCF, APC related/adenomatosis polyposis coli (APR-1)/APC, and LIT-1/NLK (loss of intestine/Nemo-like kinase). Here we explore the genetic regulatory mechanisms ...


The Decapping Scavenger Enzyme Dcs-1 Controls Microrna Levels In Caenorhabditis Elegans, Gabriel Bosse, Stefan Ruegger, Maria Ow, Alejandro Vasquez-Rifo, Evelyne Rondeau, Victor Ambros, Helge Grosshans, Martin Simard Oct 2015

The Decapping Scavenger Enzyme Dcs-1 Controls Microrna Levels In Caenorhabditis Elegans, Gabriel Bosse, Stefan Ruegger, Maria Ow, Alejandro Vasquez-Rifo, Evelyne Rondeau, Victor Ambros, Helge Grosshans, Martin Simard

Victor R. Ambros

In metazoans, microRNAs play a critical role in the posttranscriptional regulation of genes required for cell proliferation and differentiation. MicroRNAs themselves are regulated by a multitude of mechanisms influencing their transcription and posttranscriptional maturation. However, there is only sparse knowledge on pathways regulating the mature, functional form of microRNA. Here, we uncover the implication of the decapping scavenger protein DCS-1 in the control of microRNA turnover. In Caenorhabditis elegans, mutations in dcs-1 increase the levels of functional microRNAs. We demonstrate that DCS-1 interacts with the exonuclease XRN-1 to promote microRNA degradation in an independent manner from its known decapping scavenger ...


Developmental Decline In Neuronal Regeneration By The Progressive Change Of Two Intrinsic Timers, Yan Zou, Hui Chiu, Anna Zinovyeva, Victor Ambros, Chiou-Fen Chuang, Chieh Chang Oct 2015

Developmental Decline In Neuronal Regeneration By The Progressive Change Of Two Intrinsic Timers, Yan Zou, Hui Chiu, Anna Zinovyeva, Victor Ambros, Chiou-Fen Chuang, Chieh Chang

Victor R. Ambros

Like mammalian neurons, Caenorhabditis elegans neurons lose axon regeneration ability as they age, but it is not known why. Here, we report that let-7 contributes to a developmental decline in anterior ventral microtubule (AVM) axon regeneration. In older AVM axons, let-7 inhibits regeneration by down-regulating LIN-41, an important AVM axon regeneration-promoting factor. Whereas let-7 inhibits lin-41 expression in older neurons through the lin-41 3' untranslated region, lin-41 inhibits let-7 expression in younger neurons through Argonaute ALG-1. This reciprocal inhibition ensures that axon regeneration is inhibited only in older neurons. These findings show that a let-7-lin-41 regulatory circuit, which was previously ...


The Evolution Of Our Thinking About Micrornas, Victor Ambros Oct 2015

The Evolution Of Our Thinking About Micrornas, Victor Ambros

Victor R. Ambros

Our appreciation of the significance of microRNAs to biology at large continues to be an evolving process.


The Developmental Timing Regulator Hbl-1 Modulates The Dauer Formation Decision In Caenorhabditis Elegans, Xantha Karp, Victor Ambros Oct 2015

The Developmental Timing Regulator Hbl-1 Modulates The Dauer Formation Decision In Caenorhabditis Elegans, Xantha Karp, Victor Ambros

Victor R. Ambros

Animals developing in the wild encounter a range of environmental conditions, and so developmental mechanisms have evolved that can accommodate different environmental contingencies. Harsh environmental conditions cause Caenorhabditis elegans larvae to arrest as stress-resistant "dauer" larvae after the second larval stage (L2), thereby indefinitely postponing L3 cell fates. HBL-1 is a key transcriptional regulator of L2 vs. L3 cell fate. Through the analysis of genetic interactions between mutations of hbl-1 and of genes encoding regulators of dauer larva formation, we find that hbl-1 can also modulate the dauer formation decision in a complex manner. We propose that dynamic interactions between ...


Mir-14 Regulates Autophagy During Developmental Cell Death By Targeting Ip3-Kinase 2, Charles Nelson, Victor Ambros, Eric Baehrecke Oct 2015

Mir-14 Regulates Autophagy During Developmental Cell Death By Targeting Ip3-Kinase 2, Charles Nelson, Victor Ambros, Eric Baehrecke

Victor R. Ambros

Macroautophagy (autophagy) is a lysosome-dependent degradation process that has been implicated in age-associated diseases. Autophagy is involved in both cell survival and cell death, but little is known about the mechanisms that distinguish its use during these distinct cell fates. Here, we identify the microRNA miR-14 as being both necessary and sufficient for autophagy during developmentally regulated cell death in Drosophila. Loss of miR-14 prevented induction of autophagy during salivary gland cell death, but had no effect on starvation-induced autophagy in the fat body. Moreover, misexpression of miR-14 was sufficient to prematurely induce autophagy in salivary glands, but not in ...


Circulating Micrornas In Cardiovascular Disease, David Mcmanus, Victor Ambros Oct 2015

Circulating Micrornas In Cardiovascular Disease, David Mcmanus, Victor Ambros

Victor R. Ambros

Comment on: Transcoronary concentration gradients of circulating microRNAs. [Circulation. 2011]


Micrornas And Developmental Timing, Victor Ambros Oct 2015

Micrornas And Developmental Timing, Victor Ambros

Victor R. Ambros

MicroRNAs regulate temporal transitions in gene expression associated with cell fate progression and differentiation throughout animal development. Genetic analysis of developmental timing in the nematode Caenorhabditis elegans identified two evolutionarily conserved microRNAs, lin-4/mir-125 and let-7, that regulate cell fate progression and differentiation in C. elegans cell lineages. MicroRNAs perform analogous developmental timing functions in other animals, including mammals. By regulating cell fate choices and transitions between pluripotency and differentiation, microRNAs help to orchestrate developmental events throughout the developing animal, and to play tissue homeostasis roles important for disease, including cancer.


Dauer Larva Quiescence Alters The Circuitry Of Microrna Pathways Regulating Cell Fate Progression In C. Elegans, Xantha Karp, Victor Ambros Oct 2015

Dauer Larva Quiescence Alters The Circuitry Of Microrna Pathways Regulating Cell Fate Progression In C. Elegans, Xantha Karp, Victor Ambros

Victor R. Ambros

In C. elegans larvae, the execution of stage-specific developmental events is controlled by heterochronic genes, which include those encoding a set of transcription factors and the microRNAs that regulate the timing of their expression. Under adverse environmental conditions, developing larvae enter a stress-resistant, quiescent stage called 'dauer'. Dauer larvae are characterized by the arrest of all progenitor cell lineages at a stage equivalent to the end of the second larval stage (L2). If dauer larvae encounter conditions favorable for resumption of reproductive growth, they recover and complete development normally, indicating that post-dauer larvae possess mechanisms to accommodate an indefinite period ...


Mirwip: Microrna Target Prediction Based On Microrna-Containing Ribonucleoprotein-Enriched Transcripts, Molly Hammell, Dang Long, Liang Zhang, Andrew Lee, C. Steven Carmack, Min Han, Ye Ding, Victor Ambros Oct 2015

Mirwip: Microrna Target Prediction Based On Microrna-Containing Ribonucleoprotein-Enriched Transcripts, Molly Hammell, Dang Long, Liang Zhang, Andrew Lee, C. Steven Carmack, Min Han, Ye Ding, Victor Ambros

Victor R. Ambros

Target prediction for animal microRNAs (miRNAs) has been hindered by the small number of verified targets available to evaluate the accuracy of predicted miRNA-target interactions. Recently, a dataset of 3,404 miRNA-associated mRNA transcripts was identified by immunoprecipitation of the RNA-induced silencing complex components AIN-1 and AIN-2. Our analysis of this AIN-IP dataset revealed enrichment for defining characteristics of functional miRNA-target interactions, including structural accessibility of target sequences, total free energy of miRNA-target hybridization and topology of base-pairing to the 5' seed region of the miRNA. We used these enriched characteristics as the basis for a quantitative miRNA target prediction ...


Systematic Analysis Of Dynamic Mirna-Target Interactions During C. Elegans Development, Liang Zhang, Molly Hammell, Brian Kudlow, Victor Ambros, Min Han Oct 2015

Systematic Analysis Of Dynamic Mirna-Target Interactions During C. Elegans Development, Liang Zhang, Molly Hammell, Brian Kudlow, Victor Ambros, Min Han

Victor R. Ambros

Although microRNA (miRNA)-mediated functions have been implicated in many aspects of animal development, the majority of miRNA::mRNA regulatory interactions remain to be characterized experimentally. We used an AIN/GW182 protein immunoprecipitation approach to systematically analyze miRNA::mRNA interactions during C. elegans development. We characterized the composition of miRNAs in functional miRNA-induced silencing complexes (miRISCs) at each developmental stage and identified three sets of miRNAs with distinct stage-specificity of function. We then identified thousands of miRNA targets in each developmental stage, including a significant portion that is subject to differential miRNA regulation during development. By identifying thousands of miRNA ...


Immunopurification Of Ago1 Mirnps Selects For A Distinct Class Of Microrna Targets, Xin Hong, Molly Hammell, Victor Ambros, Stephen Cohen Oct 2015

Immunopurification Of Ago1 Mirnps Selects For A Distinct Class Of Microrna Targets, Xin Hong, Molly Hammell, Victor Ambros, Stephen Cohen

Victor R. Ambros

microRNAs comprise a few percent of animal genes and have been recognized as important regulators of a diverse range of biological processes. Understanding the biological functions of miRNAs requires effective means to identify their targets. Combined efforts from computational prediction, miRNA over-expression or depletion, and biochemical purification have identified thousands of potential miRNA-target pairs in cells and organisms. Complementarity to the miRNA seed sequence appears to be a common principle in target recognition. Other features, including miRNA-target duplex stability, binding site accessibility, and local UTR structure might affect target recognition. Yet computational approaches using such contextual features have yielded largely ...


Micrornas: Genetically Sensitized Worms Reveal New Secrets, Victor Ambros Oct 2015

Micrornas: Genetically Sensitized Worms Reveal New Secrets, Victor Ambros

Victor R. Ambros

Why do many microRNA gene mutants display no evident phenotype? Multiply mutant worms that are selectively impaired in genetic regulatory network activities have been used to uncover previously unknown functions for numerous Caenorhabditis elegans microRNAs.


Prb/Cki Pathways At The Interface Of Cell Cycle And Development, Victor Ambros Oct 2015

Prb/Cki Pathways At The Interface Of Cell Cycle And Development, Victor Ambros

Victor R. Ambros

Comment on: The cyclin-dependent kinase inhibitors, cki-1 and cki-2, act in overlapping but distinct pathways to control cell-cycle quiescence during C. elegans development. Buck SH, et al. Cell Cycle 2009; 8:2613-20.


A Single Molecular Probe For Multi-Analyte (Cr3+, Al3+ And Fe3+) Detection In Aqueous Medium And Its Biological Application, Junfeng Wang, Yingbo Li, Nikul Patel, Ge Zhang, Demin Zhou, Yi Pang Sep 2015

A Single Molecular Probe For Multi-Analyte (Cr3+, Al3+ And Fe3+) Detection In Aqueous Medium And Its Biological Application, Junfeng Wang, Yingbo Li, Nikul Patel, Ge Zhang, Demin Zhou, Yi Pang

Yi Pang

An ESIPT based fluorescent sensor 1 was developed, which could selectively detect and differentiate trivalent metal ions Cr3+, Al3+ and Fe3+ in aqueous medium. The cell imaging experiments confirmed that 1 can be used for monitoring intracellular Cr3+ and Al3+ levels in living cells.


A Conserved Three-Nucleotide Core Motif Defines Musashi Rna Binding Specificity, Nancy Zearfoss, Laura Deveau, Carina Clingman, Eric Schmidt, Emily Johnson, Francesca Massi, Sean Ryder Sep 2015

A Conserved Three-Nucleotide Core Motif Defines Musashi Rna Binding Specificity, Nancy Zearfoss, Laura Deveau, Carina Clingman, Eric Schmidt, Emily Johnson, Francesca Massi, Sean Ryder

Sean P. Ryder

Musashi (MSI) family proteins control cell proliferation and differentiation in many biological systems. They are overexpressed in tumors of several origins, and their expression level correlates with poor prognosis. MSI proteins control gene expression by binding RNA and regulating its translation. They contain two RNA recognition motif (RRM) domains, which recognize a defined sequence element. The relative contribution of each nucleotide to the binding affinity and specificity is unknown. We analyzed the binding specificity of three MSI family RRM domains using a quantitative fluorescence anisotropy assay. We found that the core element driving recognition is the sequence UAG. Nucleotides outside ...


Allosteric Inhibition Of A Stem Cell Rna-Binding Protein By An Intermediary Metabolite, Carina Clingman, Laura Deveau, Samantha Hay, Ryan Genga, Shivender Shandilya, Francesca Massi, Sean Ryder Sep 2015

Allosteric Inhibition Of A Stem Cell Rna-Binding Protein By An Intermediary Metabolite, Carina Clingman, Laura Deveau, Samantha Hay, Ryan Genga, Shivender Shandilya, Francesca Massi, Sean Ryder

Sean P. Ryder

Gene expression and metabolism are coupled at numerous levels. Cells must sense and respond to nutrients in their environment, and specialized cells must synthesize metabolic products required for their function. Pluripotent stem cells have the ability to differentiate into a wide variety of specialized cells. How metabolic state contributes to stem cell differentiation is not understood. In this study, we show that RNA-binding by the stem cell translation regulator Musashi-1 (MSI1) is allosterically inhibited by 18-22 carbon omega-9 monounsaturated fatty acids. The fatty acid binds to the N-terminal RNA Recognition Motif (RRM) and induces a conformational change that prevents RNA ...


A Single Molecular Probe For Multi-Analyte (Cr3+, Al3+ And Fe3+) Detection In Aqueous Medium And Its Biological Application, Junfeng Wang, Yingbo Li, Nikul Patel, Ge Zhang, Demin Zhou, Yi Pang Sep 2015

A Single Molecular Probe For Multi-Analyte (Cr3+, Al3+ And Fe3+) Detection In Aqueous Medium And Its Biological Application, Junfeng Wang, Yingbo Li, Nikul Patel, Ge Zhang, Demin Zhou, Yi Pang

Ge Zhang

An ESIPT based fluorescent sensor 1 was developed, which could selectively detect and differentiate trivalent metal ions Cr3+, Al3+ and Fe3+ in aqueous medium. The cell imaging experiments confirmed that 1 can be used for monitoring intracellular Cr3+ and Al3+ levels in living cells.


Three-Dimensional Confocal Microscopy Indentation Method For Hydrogel Elasticity Measurement, Donghee Lee, Md Mahmudur Rahman, You Zhou, Sangjin Ryu Aug 2015

Three-Dimensional Confocal Microscopy Indentation Method For Hydrogel Elasticity Measurement, Donghee Lee, Md Mahmudur Rahman, You Zhou, Sangjin Ryu

Md Mahmudur Rahman

No abstract provided.


Increased Ho-1 Levels Ameliorate Fatty Liver Development Through A Reduction Of Heme And Recruitment Of Fgf21, Terry Hinds, Komal Sodhi, Charles Meadows, Nader Abraham, Larisa Fedorova, Nitin Puri, Dong Kim, Stephen Peterson, Joseph Shapiro, Attallah Kappas Jul 2015

Increased Ho-1 Levels Ameliorate Fatty Liver Development Through A Reduction Of Heme And Recruitment Of Fgf21, Terry Hinds, Komal Sodhi, Charles Meadows, Nader Abraham, Larisa Fedorova, Nitin Puri, Dong Kim, Stephen Peterson, Joseph Shapiro, Attallah Kappas

Charles Meadows

Objective Obese leptin deficient (ob/ob) mice are a model of adiposity that displays increased levels of fat, glucose, and liver lipids. Our hypothesis is that HO-1 overexpression ameliorates fatty liver development. Methods Obese mice were administered cobalt protoporphyrin (CoPP) and stannic mesoporphyrin (SnMP) for 6 weeks. Heme, HO-1, HO activity, PGC1α, FGF21, glycogen content, and lipogenesis were assessed. Results CoPP administration increased hepatic HO-1 protein levels and HO activity, decreased hepatic heme, body weight gain, glucose levels, and resulted in decreased steatosis. Increased levels of HO-1 produced a decrease in lipid droplet size, Fatty acid synthase (FAS) levels involving ...


Increased Ho-1 Levels Ameliorate Fatty Liver Development Through A Reduction Of Heme And Recruitment Of Fgf21, Terry Hinds, Komal Sodhi, Charles Meadows, Nader Abraham, Larisa Fedorova, Nitin Puri, Dong Kim, Stephen Peterson, Joseph Shapiro, Attallah Kappas Jul 2015

Increased Ho-1 Levels Ameliorate Fatty Liver Development Through A Reduction Of Heme And Recruitment Of Fgf21, Terry Hinds, Komal Sodhi, Charles Meadows, Nader Abraham, Larisa Fedorova, Nitin Puri, Dong Kim, Stephen Peterson, Joseph Shapiro, Attallah Kappas

Nader G. Abraham

Objective Obese leptin deficient (ob/ob) mice are a model of adiposity that displays increased levels of fat, glucose, and liver lipids. Our hypothesis is that HO-1 overexpression ameliorates fatty liver development. Methods Obese mice were administered cobalt protoporphyrin (CoPP) and stannic mesoporphyrin (SnMP) for 6 weeks. Heme, HO-1, HO activity, PGC1α, FGF21, glycogen content, and lipogenesis were assessed. Results CoPP administration increased hepatic HO-1 protein levels and HO activity, decreased hepatic heme, body weight gain, glucose levels, and resulted in decreased steatosis. Increased levels of HO-1 produced a decrease in lipid droplet size, Fatty acid synthase (FAS) levels involving ...


Cyclooxygenase-2 Dependent Metabolism Of 20-Hete Increases Adiposity And Adipocyte Enlargement In Mesenchymal Stem Cell-Derived Adipocytes, Dong Kim, Nitin Puri, Komal Sodhi, John Falck, Nader Abraham, Joseph Shapiro, Michal Schwartzman Jul 2015

Cyclooxygenase-2 Dependent Metabolism Of 20-Hete Increases Adiposity And Adipocyte Enlargement In Mesenchymal Stem Cell-Derived Adipocytes, Dong Kim, Nitin Puri, Komal Sodhi, John Falck, Nader Abraham, Joseph Shapiro, Michal Schwartzman

Nader G. Abraham

Abstract 20-Hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE), a product of the cytochrome P450 (CYP)-catalyzed [1] -hydroxylation of arachidonic acid, induces oxidative stress and, in clinical studies, is associated with increased body mass index (BMI) and the metabolic syndrome. This study was designed to examine the effects of exogenous 20- HETE on mesenchymal stem cell (MSC)-derived adipocytes. The expression levels of CYP4A11 and CYP4F2 (major 20-HETE synthases in humans) in MSCs decreased during adipocyte differentiation; however, exogenous administration of 20-HETE (0.1–1 M) increased adipogenesis in a dose dependent manner in these cells ( P < 0.05). The inability ...


Gender Differences In The Development Of Uremic Cardiomyopathy Following Partial Nephrectomy: Role Of Progesterone, Christopher Drummond, George Buddny, Steven Haller, Jiang Liu, Yanling Yan, Zijian Xie, Deepak Malhotra, Joseph Shapiro, Jiang Tian Jul 2015

Gender Differences In The Development Of Uremic Cardiomyopathy Following Partial Nephrectomy: Role Of Progesterone, Christopher Drummond, George Buddny, Steven Haller, Jiang Liu, Yanling Yan, Zijian Xie, Deepak Malhotra, Joseph Shapiro, Jiang Tian

Zijian Xie

Gender difference has been suggested as a risk factor for developing cardiovascular and renal diseases in humans and experimental animals. As a major sex hormone, progesterone was reported to compete with cardiotonic steroid binding to Na/K-ATPase. Our previous publication demonstrated that cardiotonic steroids (e.g., marinobufagenin) play an important role in the development of experimental uremic cardiomyopathy. We also observed that the putative mineralocorticoid antagonists, spironolactone and its major metabolite canrenone, antagonize binding of cardiotonic steroids to Na/K-ATPase in a competitive manner and also ameliorate experimental uremic cardiomyopathy induced by partial nephrectomy. In the following studies, we noted ...


Pgf2Α-Associated Vascular Smooth Muscle Hypertrophy Is Ros Dependent And Involves The Activation Of Mtor, P70s6k, And Pten, Kevin Rice, Sreevani Uddemarri, Devashish Desai, Ryan Morrison, R. Harris, Eric Blough Jul 2015

Pgf2Α-Associated Vascular Smooth Muscle Hypertrophy Is Ros Dependent And Involves The Activation Of Mtor, P70s6k, And Pten, Kevin Rice, Sreevani Uddemarri, Devashish Desai, Ryan Morrison, R. Harris, Eric Blough

Kevin M Rice

Prostaglandin F2α (PGF2α) increases reactive oxygen species (ROS) and induces vascular smooth muscle cell (VSMC) hypertrophy by largely unknown mechanism(s). To investigate the signaling events governing PGF2α –induced VSMC hypertrophy we examined the ability of the PGF2α analog, fluprostenol to elicit phosphorylation of Akt, the mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6k), glycogen synthase kinase-3β (GSK-3β), phosphatase and tensin homolog (PTEN), extracellular signal-regulated kinase 1/2 (ERK1/2) and Jun N-terminal kinase (JNK) in growth arrested A7r5 VSMC. Fluprostenol-induced hypertrophy was associated with increased ROS, mTOR translocation from the nucleus to the cytoplasm, along with Akt ...