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Articles 31 - 60 of 129
Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
The Evolution Of Our Thinking About Micrornas, Victor Ambros
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.
Victor Ambros: The Broad Scope Of Micrornas. Interview By Caitlin Sedwick, Victor R. Ambros
Victor Ambros: The Broad Scope Of Micrornas. Interview By Caitlin Sedwick, Victor R. Ambros
Victor R. Ambros
Interview with Victor Ambros, who studies how microRNAs impact development.
Mutations In Conserved Residues Of The C. Elegans Microrna Argonaute Alg-1 Identify Separable Functions In Alg-1 Mirisc Loading And Target Repression, Anna Y. Zinovyeva, Samir Bouasker, Martin J. Simard, Christopher M. Hammell, Victor R. Ambros
Mutations In Conserved Residues Of The C. Elegans Microrna Argonaute Alg-1 Identify Separable Functions In Alg-1 Mirisc Loading And Target Repression, Anna Y. Zinovyeva, Samir Bouasker, Martin J. Simard, Christopher M. Hammell, Victor R. Ambros
Victor R. Ambros
microRNAs function in diverse developmental and physiological processes by regulating target gene expression at the post-transcriptional level. ALG-1 is one of two Caenorhabditis elegans Argonautes (ALG-1 and ALG-2) that together are essential for microRNA biogenesis and function. Here, we report the identification of novel antimorphic (anti) alleles of ALG-1 as suppressors of lin-28(lf) precocious developmental phenotypes. The alg-1(anti) mutations broadly impair the function of many microRNAs and cause dosage-dependent phenotypes that are more severe than the complete loss of ALG-1. ALG-1(anti) mutant proteins are competent for promoting Dicer cleavage of microRNA precursors and for associating with and stabilizing microRNAs. However, …
The Developmental Timing Regulator Hbl-1 Modulates The Dauer Formation Decision In Caenorhabditis Elegans, Xantha Karp, Victor Ambros
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
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
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
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
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 …
Circulating Micrornas Are Associated With Paroxysmal Or Persistent Atrial Fibrillation, David D. Mcmanus, Jeanine Ward, Amir Y. Shaikh, Khushleen Jaggi, Victor R. Ambros, Jane Freedman, John F. Keaney Jr.
Circulating Micrornas Are Associated With Paroxysmal Or Persistent Atrial Fibrillation, David D. Mcmanus, Jeanine Ward, Amir Y. Shaikh, Khushleen Jaggi, Victor R. Ambros, Jane Freedman, John F. Keaney Jr.
Victor R. Ambros
Introduction: Novel methods of identifying individuals at risk for atrial fibrillation (AF) are needed. MicroRNAs (MiRNAs) regulate gene expression in a number of cardiovascular diseases, including AF. It is unknown, however, if key circulating, cardiac-specific miRNAs differ between individuals with paroxysmal or persistent AF and those in sinus rhythm. Methods: 17 individuals with a history of AF were recruited prior to catheter ablation. 24 hospitalized patients in normal sinus rhythm and no history of AF comprised the control group. 94 plasma miRNAs were selected based on a priori associations with processes implicated in AF for evaluation using the TaqMan miRNA …
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
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 method, …
Circulating Cell And Plasma Microrna Profiles Differ Between Non-St-Segment And St-Segment-Elevation Myocardial Infarction, Jeanine Ward, Nada Esa, Rahul Pidikiti, Jane E. Freedman, John F. Keaney, Kahraman Tanriverdi, Olga Vitseva, Victor R. Ambros, Rosalind Lee, David D. Mcmanus
Circulating Cell And Plasma Microrna Profiles Differ Between Non-St-Segment And St-Segment-Elevation Myocardial Infarction, Jeanine Ward, Nada Esa, Rahul Pidikiti, Jane E. Freedman, John F. Keaney, Kahraman Tanriverdi, Olga Vitseva, Victor R. Ambros, Rosalind Lee, David D. Mcmanus
Victor R. Ambros
BACKGROUND: Differences in plasma and whole blood expression microRNAs (miRNAs) in patients with an acute coronary syndrome (ACS) have been determined in both in vitro and in vivo studies. Although most circulating miRNAs are located in the cellular components of whole blood, little is known about the miRNA profiles of whole blood subcomponents, including plasma, platelets and leukocytes in patients with myocardial ischemia. METHODS: Thirteen patients with a ST-segment-elevation (STEMI) or non-ST-segment elevation (NSTEMI) myocardial infarction were identified in the University of Massachusetts Medical Center Emergency Department (ED) or cardiac catheterization laboratory between February and June of 2012. Whole blood …
The Embryonic Mir-35 Family Of Micrornas Promotes Multiple Aspects Of Fecundity In Caenorhabditis Elegans, Katherine Mcjunkin, Victor R. Ambros
The Embryonic Mir-35 Family Of Micrornas Promotes Multiple Aspects Of Fecundity In Caenorhabditis Elegans, Katherine Mcjunkin, Victor R. Ambros
Victor R. Ambros
MicroRNAs guide many aspects of development in all metazoan species. Frequently, microRNAs are expressed during a specific developmental stage to perform a temporally defined function. The C. elegans mir-35-42 microRNAs are expressed abundantly in oocytes and early embryos and are essential for embryonic development. Here, we show that these embryonic microRNAs surprisingly also function to control the number of progeny produced by adult hermaphrodites. Using a temperature-sensitive mir-35-42 family mutant (a deletion of the mir-35-41 cluster), we demonstrate three distinct defects in hermaphrodite fecundity. At permissive temperatures, a mild sperm defect partially reduces hermaphrodite fecundity. At restrictive temperatures, somatic gonad …
An Efficient And Sensitive Method For Preparing Cdna Libraries From Scarce Biological Samples, Catherine H. Sterling, Isana Veksler-Lublinsky, Victor R. Ambros
An Efficient And Sensitive Method For Preparing Cdna Libraries From Scarce Biological Samples, Catherine H. Sterling, Isana Veksler-Lublinsky, Victor R. Ambros
Victor R. Ambros
The preparation and high-throughput sequencing of cDNA libraries from samples of small RNA is a powerful tool to quantify known small RNAs (such as microRNAs) and to discover novel RNA species. Interest in identifying the small RNA repertoire present in tissues and in biofluids has grown substantially with the findings that small RNAs can serve as indicators of biological conditions and disease states. Here we describe a novel and straightforward method to clone cDNA libraries from small quantities of input RNA. This method permits the generation of cDNA libraries from sub-picogram quantities of RNA robustly, efficiently and reproducibly. We demonstrate …
Systematic Analysis Of Dynamic Mirna-Target Interactions During C. Elegans Development, Liang Zhang, Molly Hammell, Brian Kudlow, Victor Ambros, Min Han
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 family-mRNA pairs with temporally …
Immunopurification Of Ago1 Mirnps Selects For A Distinct Class Of Microrna Targets, Xin Hong, Molly Hammell, Victor Ambros, Stephen Cohen
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 …
Drosophila Let-7 Microrna Is Required For Remodeling Of The Neuromusculature During Metamorphosis, Nicholas S. Sokol, Peizhang Xu, Yuh-Nung Jan, Victor R. Ambros
Drosophila Let-7 Microrna Is Required For Remodeling Of The Neuromusculature During Metamorphosis, Nicholas S. Sokol, Peizhang Xu, Yuh-Nung Jan, Victor R. Ambros
Victor R. Ambros
The Drosophila let-7-Complex (let-7-C) is a polycistronic locus encoding three ancient microRNAs: let-7, miR-100, and fly lin-4 (miR-125). We find that the let-7-C locus is principally expressed in the pupal and adult neuromusculature. let-7-C knockout flies appear normal externally but display defects in adult behaviors (e.g., flight, motility, and fertility) as well as clear juvenile features in their neuromusculature. We find that the function of let-7-C to ensure the appropriate remodeling of the abdominal neuromusculature during the larval-to-adult transition is carried out predominantly by let-7 alone. This heterochronic role of let-7 is likely just one of the ways in which …
Effect Of Life History On Microrna Expression During C. Elegans Development, Xantha Karp, Molly Hammell, Maria C. Ow, Victor R. Ambros
Effect Of Life History On Microrna Expression During C. Elegans Development, Xantha Karp, Molly Hammell, Maria C. Ow, Victor R. Ambros
Victor R. Ambros
Animals have evolved mechanisms to ensure the robustness of developmental outcomes to changing environments. MicroRNA expression may contribute to developmental robustness because microRNAs are key post-transcriptional regulators of developmental gene expression and can affect the expression of multiple target genes. Caenorhabditis elegans provides an excellent model to study developmental responses to environmental conditions. In favorable environments, C. elegans larvae develop rapidly and continuously through four larval stages. In contrast, in unfavorable conditions, larval development may be interrupted at either of two diapause stages: The L1 diapause occurs when embryos hatch in the absence of food, and the dauer diapause occurs …
Micrornas: Genetically Sensitized Worms Reveal New Secrets, Victor Ambros
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.
In The Tradition Of Science: An Interview With Victor Ambros, Victor R. Ambros
In The Tradition Of Science: An Interview With Victor Ambros, Victor R. Ambros
Victor R. Ambros
No abstract provided.
Prb/Cki Pathways At The Interface Of Cell Cycle And Development, Victor Ambros
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
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
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
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
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
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.
Crosstalk Between Brca-Fanconi Anemia And Mismatch Repair Pathways Prevents Msh2-Dependent Aberrant Dna Damage Responses, Min Peng, Jenny X. Xie, Anna J. Ucher, Janet Stavnezer, Sharon B. Cantor
Crosstalk Between Brca-Fanconi Anemia And Mismatch Repair Pathways Prevents Msh2-Dependent Aberrant Dna Damage Responses, Min Peng, Jenny X. Xie, Anna J. Ucher, Janet Stavnezer, Sharon B. Cantor
Janet M. Stavnezer
Several proteins in the BRCA-Fanconi anemia (FA) pathway, such as FANCJ, BRCA1, and FANCD2, interact with mismatch repair (MMR) pathway factors, but the significance of this link remains unknown. Unlike the BRCA-FA pathway, the MMR pathway is not essential for cells to survive toxic DNA interstrand crosslinks (ICLs), although MMR proteins bind ICLs and other DNA structures that form at stalled replication forks. We hypothesized that MMR proteins corrupt ICL repair in cells that lack crosstalk between BRCA-FA and MMR pathways. Here, we show that ICL sensitivity of cells lacking the interaction between FANCJ and the MMR protein MLH1 is …
A Study On Garments Dyeing With Direct Dyes And Pigments In Bangladesh, Tanushree Saha, Rasheda Begum Dina
A Study On Garments Dyeing With Direct Dyes And Pigments In Bangladesh, Tanushree Saha, Rasheda Begum Dina
Innovative Research Publications IRP India
Garment dyeing has been practiced for many years, both commercially and as a home procedure. Recently, interest in this technique has increased since it makes possible to give rapidest response to consumer demand, reduces lead times and inventory. To establish a profitable garment dyeing plant, all manufacturing steps must be carefully controlled. In this paper, we have tried to give an idea about the process of using different types of dyes in garments dyeing and their fastness properties.
Alkylphenol Contamination In Homarus Americanus, Jennifer Renee Urban
Alkylphenol Contamination In Homarus Americanus, Jennifer Renee Urban
Jennifer M. Urban
Alkylphenols are pollutants that are present in marine sediments and fishes. In earlier work it has been discovered that alkylphenols are present in the Homarus americanus, or the American lobster. Research suggests that alkylphenols could behave as endocrine disruptors as they have been found to affect juvenile hormone activity. It has been hypothesized that lobsters may be able to rid themselves of alkylphenol contamination through secreting these compounds into the environment or sequestering them in their tissues. In this study, I address the question of how lobsters may rid themselves of alkylphenols by analyzing hemolymph, muscle, gill, and shell samples …
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
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 recruitment …
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
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 recruitment …