Open Access. Powered by Scholars. Published by Universities.®

Biochemistry, Biophysics, and Structural Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 30 of 34

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

Immediate-Early Genes And Delayed Primary Response Genes Regulated By Nmu In Skbr3 Her-2 Positive Breast Cancer Cell Line, Jessica Murphy, Sweta Rani Sep 2019

Immediate-Early Genes And Delayed Primary Response Genes Regulated By Nmu In Skbr3 Her-2 Positive Breast Cancer Cell Line, Jessica Murphy, Sweta Rani

Sure-J: Science Undergraduate Research Journal

Background
Breast cancer is a heterogeneous disease that consists of varying genetic, cellular and molecular subtypes with unique characteristics. Due to the multiple subtypes and molecular markers of breast cancer, successful clinical treatment is hampered by the lack of reliable biomarkers. HER2-positive breast cancer is an aggressive subtype associated with poor patient prognosis. Although survival rates have dramatically increased due to the development of Trastuzumab in 1997, many patients develop a resistance to this therapeutic treatment and relapse over time. Rani et al. (2014), have associated the acquirement of resistance to HER2-treatment with Neuromedin U, but the mechanisms by which ...


Dietary Phytochemicals As Inhibitors Of Primary Amine Oxidase, Padraig Shanahan, Jeffrey O'Sullivan, Keith F. Tipton, Gemma Kinsella, Barry J. Ryan, Gary T. Henehan Aug 2017

Dietary Phytochemicals As Inhibitors Of Primary Amine Oxidase, Padraig Shanahan, Jeffrey O'Sullivan, Keith F. Tipton, Gemma Kinsella, Barry J. Ryan, Gary T. Henehan

Articles

Phytochemicals such as methylxanthines, catechins and polyphenols show health benefits in a range of diseases although their mechanism of action is not fully understood. Primary Amine Oxidase (PrAO) is widely recognised as a therapeutic drug target for the treatment of inflammatory, vascular and neurodegenerative diseases. Previous work in our laboratories showed that caffeine inhibited bovine PrAO activity with a Ki of 1.0mM. In the present study we examined a range of methylxanthines and catechins as inhibitors of bovine PrAO. The methylxanthines tested were caffeine, paraxanthine, theophylline, theobromine and 7-methylxanthine. Of these, only theobromine was an inhibitor with an IC50 ...


Disrupted Superior Collicular Activity May Reveal Cervical Dystonia Disease Pathomechanisms, Eavan M. Mcgovern, Owen Killian, Shruti Narashimham, Brendan Quinlivan, John Butler, Rebecca Beck, Ines Beiser, Laura W. Williams, Ronan P. Killeen, Michael Farrell, Sean O'Riordan, Richard B. Reilly, Michael Hutchinson Jan 2017

Disrupted Superior Collicular Activity May Reveal Cervical Dystonia Disease Pathomechanisms, Eavan M. Mcgovern, Owen Killian, Shruti Narashimham, Brendan Quinlivan, John Butler, Rebecca Beck, Ines Beiser, Laura W. Williams, Ronan P. Killeen, Michael Farrell, Sean O'Riordan, Richard B. Reilly, Michael Hutchinson

Articles

Cervical dystonia is a common neurological movement disorder characterised by muscle contractions causing abnormal movements and postures affecting the head and neck. The neural networks underpinning this condition are incompletely understood. While animal models suggest a role for the superior colliculus in its pathophysiology, this link has yet to be established in humans. The present experiment was designed to test the hypothesis that disrupted superior collicular processing is evident in affected patients and in relatives harbouring a disease-specific endophenotype (abnormal temporal discrimination). The study participants were 16 cervical dystonia patients, 16 unaffected first-degree relatives with abnormal temporal discrimination, 16 unaffected ...


Non-Thermal Atmospheric Plasma Induces Ros-Independent Cell Death In U373mg Glioma Cells And Augments The Cytotoxicity Of Temozolomide, Gillian Conway, Alan Casey, Vladimir Milosavljevic, Yupeng Liu, Orla L. Howe, Patrick Cullen, James Curtin Feb 2016

Non-Thermal Atmospheric Plasma Induces Ros-Independent Cell Death In U373mg Glioma Cells And Augments The Cytotoxicity Of Temozolomide, Gillian Conway, Alan Casey, Vladimir Milosavljevic, Yupeng Liu, Orla L. Howe, Patrick Cullen, James Curtin

Articles

Non-thermal atmospheric plasma (NTAP) is an ionised gas produced under high voltage that can generate short-lived chemically active species and induce a cytotoxic insult in cancer cells. Cell-specific resistance to NTAP-mediated cytotoxicity has been reported in the literature. The aim of this study was to determine whether resistance against NTAP could be overcome using the human glioma cell line U373MG.

Methods:

Non-thermal atmospheric plasma was generated using a Dielectric Barrier Device (DBD) system with a maximum voltage output of 120 kV at 50 Hz. The viability of U373MG GBM cells and HeLa cervical carcinoma cells was determined using morphology, flow ...


Current Advances In The Application Of Raman Spectroscopy For Molecular Diagnosis Of Cervical Cancer, Ines Martins Ramos, Alison Malkin, Fiona Lyng Jan 2015

Current Advances In The Application Of Raman Spectroscopy For Molecular Diagnosis Of Cervical Cancer, Ines Martins Ramos, Alison Malkin, Fiona Lyng

Articles

Raman spectroscopy provides a unique biochemical fingerprint capable of identifying and characterizing the structure of molecules, cells and tissues. In cervical cancer, it is acknowledged as a promising biochemical tool due to its ability to detect pre-malignancy and early malignancy stages. This review summarizes the key research in the area and the evidence compiled is very encouraging for ongoing and further research. In addition to the diagnostic potential, promising results for HPV detection and monitoring treatment response suggest more than just a diagnosis prospective. A greater body of evidence is however necessary before Raman spectroscopy is fully validated for clinical ...


Numerical Simulations Of In Vitro Nanoparticle Toxicity – The Case Of Poly(Amido Amine) Dendrimers., Marcus Maher, Pratap Naha, Sourav Prasanna Mukherjee, Hugh Byrne Dec 2014

Numerical Simulations Of In Vitro Nanoparticle Toxicity – The Case Of Poly(Amido Amine) Dendrimers., Marcus Maher, Pratap Naha, Sourav Prasanna Mukherjee, Hugh Byrne

Articles

A phenomenological rate equation model is constructed to numerically simulate nanoparticle uptake and subsequent cellular response. Polyamidoamine dendrimers (generations 4-6) are modelled and the temporal evolution of the intracellular cascade of; increased levels of reactive oxygen species, intracellular antioxidant species, caspase activation, mitochondrial membrane potential decay, tumour necrosis factor and interleukin generation is simulated, based on experimental observations.

The dose and generation dependence of several of these response factors are seen to well represent experimental observations at a range of time points. The model indicates that variations between responses of different cell-lines, including murine macrophages, human keratinocytes and colon cells ...


Acrylamide Reduction In Potato Chips By Selection Of Potato Variety Grown In Iran And Processing Conditions, S. Shojaee-Aliabadi, Hooshang Nikoopour, Farzad Kobarfard, Mahdi Parsapour, Maryam Moslehishad, Hassan Hassanabadi, Jesus Maria Frias, Maryam Hashemi, Ezzat Dahaghin Aug 2013

Acrylamide Reduction In Potato Chips By Selection Of Potato Variety Grown In Iran And Processing Conditions, S. Shojaee-Aliabadi, Hooshang Nikoopour, Farzad Kobarfard, Mahdi Parsapour, Maryam Moslehishad, Hassan Hassanabadi, Jesus Maria Frias, Maryam Hashemi, Ezzat Dahaghin

Articles

Background

Acrylamide as a possible carcinogen is known to form in heated carbohydrate-rich food such as potato chips. In this study, the effect of three potato varieties (Agria, Sante and Savalan) and two blanching conditions ((75˚C for 9 min and 83˚C for 2.5 min) on the concentration of precursors and acrylamide reduction in potato chips was investigated.

Results

Results revealed that potato variety and blanching time-temperature ere important parameters for acrylamide formation in potato chips. Acrylamide content in Sante variety potatoes, which contained the highest amount of reducing sugars, was found to be the highest (8825μg/kg ...


Divergent Mechanisms Of Interaction Of Helicobacter Pylori And Campylobacter Jejuni With Mucus And Mucins, Julie Ann Naughton, Karina Mariño, Brendan Dolan, Colm Reid, Ronan Gough, Mary Gallagher, Michelle Kilcoyne, Jared Gerlachscience,, Lokesh Joshi, Pauline Rudd, Stephen Carrington, Billy Bourke, Marguerite Clyne Aug 2013

Divergent Mechanisms Of Interaction Of Helicobacter Pylori And Campylobacter Jejuni With Mucus And Mucins, Julie Ann Naughton, Karina Mariño, Brendan Dolan, Colm Reid, Ronan Gough, Mary Gallagher, Michelle Kilcoyne, Jared Gerlachscience,, Lokesh Joshi, Pauline Rudd, Stephen Carrington, Billy Bourke, Marguerite Clyne

Articles

Helicobacter pylori and Campylobacter jejuni colonize the stomach and intestinal mucus, respectively. Using a combination of mucus-secreting cells, purified mucins, and a novel mucin microarray platform, we examined the interactions of these two organisms with mucus and mucins. H. pylori and C. jejuni bound to distinctly different mucins. C. jejuni displayed a striking tropism for chicken gastrointestinal mucins compared to mucins from other animals and preferentially bound mucins from specific avian intestinal sites (in order of descending preference: the large intestine, proximal small intestine, and cecum). H. pylori bound to a number of animal mucins, including porcine stomach mucin, but ...


Novel Cis-Restricted Β-Lactam Combretastatin A-4 Analogues Display Anti-Vascular And Anti-Metastatic Properties In Vitro, Seema M. Nathwani, Lisa M. Greene, Linda Hughes, Miriam Carr, Niamh O'Boyle, Susan Mcdonnell, Mary J. Meegan, Daniela M. Zisterer Jan 2013

Novel Cis-Restricted Β-Lactam Combretastatin A-4 Analogues Display Anti-Vascular And Anti-Metastatic Properties In Vitro, Seema M. Nathwani, Lisa M. Greene, Linda Hughes, Miriam Carr, Niamh O'Boyle, Susan Mcdonnell, Mary J. Meegan, Daniela M. Zisterer

Articles

No abstract provided.


Bacterial Host Interactions In Cystic Fibrosis, Máire Callaghan, Siobhan Mcclean Jan 2012

Bacterial Host Interactions In Cystic Fibrosis, Máire Callaghan, Siobhan Mcclean

Articles

Chronic infection is a hallmark of cystic fibrosis (CF) and the main contributor to morbidity. Microbial infection in CF is complex, due to the number of different species that colonise the CF lung. Their colonisation is facilitated by a host response that is impaired or compromised by highly viscous mucous, zones of hypoxia and the lack of the cystic fibrosis transmembrane regulator (CFTR). Successful dominant CF pathogens combine an effective arsenal to establish infection and counter-attack the host response, together with an ability to adapt readily to an unfavourable environment. Hypermutability is common among CF pathogens facilitating adaptation and as ...


Combretazet-3 A Novel Synthetic Cis-Stable Combretastatin-A4-Azetidinone Hybrid With Enhanced Stabilityand Therapeutic Efficacy In Colon Cancer, Lisa M. Greene, Shu Wang, Niamh O'Boyle, Sandra A. Bright, Jane E. Reid, Patrick Kelly, Mary J. Meegan, Daniela M. Zisterer Jan 2012

Combretazet-3 A Novel Synthetic Cis-Stable Combretastatin-A4-Azetidinone Hybrid With Enhanced Stabilityand Therapeutic Efficacy In Colon Cancer, Lisa M. Greene, Shu Wang, Niamh O'Boyle, Sandra A. Bright, Jane E. Reid, Patrick Kelly, Mary J. Meegan, Daniela M. Zisterer

Articles

In recent years an extensive series of synthetic combretastatin A-4 (CA-4)-azetidinone (β-lactam) hybrids were designed and synthesised with a view to improve the stability, therapeutic efficacy and aqueous solubility of CA-4. Lead compounds containing a 3,4,5-trimethoxy aromatic ring at position 1 and a variety of substitution patterns at positions 3 and 4 of the β-lactam ring were screened in three adenocarcinoma-derived colon cancer cell lines (CT-26, Caco-2 and the CA-4 resistant cell line, HT-29). In both CT-26 and Caco-2 cells all β-lactam analogues analysed displayed potent therapeutic efficacy within the nanomolar range. Substitution of the ethylene bridge ...


Differential Precipitation And Solubilization Of Proteins., Barry Ryan Jan 2011

Differential Precipitation And Solubilization Of Proteins., Barry Ryan

Books/Book Chapters

Differential protein precipitation is a rapid and economical step in protein purification and is based on exploiting the inherent physico-chemical properties of the polypeptide. Precipitation of recombinant proteins, lysed from the host cell, is commonly used to concentrate the protein of choice before further polishing steps with more selective purification columns (e.g. His-Tag, Size Exclusion etc.). Recombinant proteins can also precipitate naturally as inclusion bodies due to various influences during over-expression in the host cell. Although this phenomenon permits easier initial separation from native proteins, these inclusion bodies must carefully be differentially solubilised so as to reform functional, correctly ...


Expression Of Genes Involved In A Radiation-Induced Bystander Effect, Hayley Furlong Jan 2011

Expression Of Genes Involved In A Radiation-Induced Bystander Effect, Hayley Furlong

Conference Papers

The radiation induced bystander effect is relevant to carcinogenesis, it may have significant implications for risk estimation for radiation exposure. Currently the mechanisms and cellular events are the subject of intense investigation, because little is known. It is thought that the radiation induced bystander response is due to a bystander factor secreted in the medium post irradiation. However the biological nature of this factor is currently unknown, but it is thought to be a protein of some sort that may be involved in the apoptosis cascade. Materials and Methods: HaCaT epithelial cells were used in this study and exposed to ...


Avoiding Proteolysis During Protein Chromatography., Barry Ryan Jan 2011

Avoiding Proteolysis During Protein Chromatography., Barry Ryan

Books/Book Chapters

All cells contain proteases which effect catalytic hydrolysis of the peptide bond between amino acids in the protein backbone. Typically, proteinases are prevented from non-specific proteolysis by regulation and physical separation into different sub-cellular compartments; however, this segregation is not retained during cell lysis to release a protein of interest. Prevention of proteolysis during protein purification often takes the form of a two-pronged approach; firstly inhibition of proteolysis in situ, followed by the separation of the protease from the protein of interest via chromatographical purification. Proteinase inhibitors are routinely used to limit the effect of the proteinases before they are ...


Virulence Of An Emerging Respiratory Pathogen, Genus Pandoraea, In Vivo And Its Interactions With Lung Epithelial Cells, Gillian Herbert, Anne Costello, Lydia Fabunmi, Kirsten Schaffer, Kevin Kavanagh, Emma M. Caraher, Máire Callaghan, Siobhan Mcclean Nov 2010

Virulence Of An Emerging Respiratory Pathogen, Genus Pandoraea, In Vivo And Its Interactions With Lung Epithelial Cells, Gillian Herbert, Anne Costello, Lydia Fabunmi, Kirsten Schaffer, Kevin Kavanagh, Emma M. Caraher, Máire Callaghan, Siobhan Mcclean

Articles

Pandoraea species have emerged as opportunistic pathogens among cystic fibrosis (CF) and non-CF patients. Pandoraea pulmonicola is the predominant Pandoraea species among Irish CF patients. The objective of this study was to investigate the pathogenicity and potential mechanisms of virulence of Irish P. pulmonicola isolates and strains from other Pandoraea species. Three patients from whom the P. pulmonicola isolates were isolated have since died. The in vivo virulence of these and other Pandoraea strains was examined by determining the ability to kill Galleria mellonella larvae. The P. pulmonicola strains generally were the most virulent of the species tested, with three ...


Release Of Hmgb1 In Response To Pro-Apoptotic Glioma Killing Strategies: Efficacy And Neurotoxicity, Marianela Candolfi, Kader Yagiz, David Foulad, Gabrielle Alzadeh, Matthew Tesarfreund, Akm Ghulam Muhammad, Mariana Puntel, Kurt Kroeger, Chunyan Liu, Sharon Lee, James Curtin, Gwendalyn D. King, Jonathan Lerner, Katsuaki Sato, Yohei Mineharu, Weidong Xiong, Pedro R. Lowenstein, Maria Castro Jul 2010

Release Of Hmgb1 In Response To Pro-Apoptotic Glioma Killing Strategies: Efficacy And Neurotoxicity, Marianela Candolfi, Kader Yagiz, David Foulad, Gabrielle Alzadeh, Matthew Tesarfreund, Akm Ghulam Muhammad, Mariana Puntel, Kurt Kroeger, Chunyan Liu, Sharon Lee, James Curtin, Gwendalyn D. King, Jonathan Lerner, Katsuaki Sato, Yohei Mineharu, Weidong Xiong, Pedro R. Lowenstein, Maria Castro

Articles

Purpose In preparation for a Phase I clinical trial utilizing a combined cytotoxic/immunotherapeutic strategy using adenoviruses expressing Flt3L (Ad-Flt3L) and thymidine kinase (Ad-TK) to treat glioblastoma (GBM), we tested the hypothesis that Ad-TK+GCV would be the optimal tumor killing agent in relation to efficacy and safety when compared to other pro-apoptotic approaches. Experimental Design and Results The efficacy and neurotoxicity of Ad-TK+GCV was compared with Ads encoding the pro-apoptotic cytokines (TNF-α, TRAIL, FasL), alone or in combination with Ad-Flt3L. In rats bearing small GBMs (day 4), only Ad-TK+GCV or Ad-FasL improved survival. In rats bearing large ...


Transcriptional Regulation Of Cholesterol 24-Hydroxylase By Histone Deacetylase Inhibitors., Marjan Shafaati, Riona O'Driscoll, Ingemar Bjorkhem, Steve Meaney Jan 2009

Transcriptional Regulation Of Cholesterol 24-Hydroxylase By Histone Deacetylase Inhibitors., Marjan Shafaati, Riona O'Driscoll, Ingemar Bjorkhem, Steve Meaney

Articles

The mechanistic basis for the tissue specific expression of cholesterol elimination pathways is poorly understood. To gain additional insight into this phenomenon we considered it of interest to investigate if epigenetic mechanisms are involved in the regulation of the brain-specific enzyme cholesterol 24-hydroxylase (CYP46A1), a key regulator of brain cholesterol elimination. We demonstrated a marked time-dependent derepression of the expression of CYP46A1, in response to treatment with the potent histone deacetylase (HDAC) inhibitor Trichostatin A. The pattern of expression of the genes in the genomic region surrounding CYP46A1 was found to be diametrically opposite in brain and liver. Intraperitoneal injection ...


Hmgb1 Mediates Endogenous Tlr2 Activation And Brain Tumor Regression, James Curtin, Naiyou Liu, Marianela Candolfi, Weidong Xiong, Hikmat Assi, Kader Yagiz, Matthew Edwards, Kathrin Michelsen, Kurt Kroeger, Chunyan Liu, Akm Ghulam Muhammad, Mary Clark, Moshe Arditi, Begonya Comin-Anduix, Antoni Ribas, Pedro Lowenstein, Maria Castro Jan 2009

Hmgb1 Mediates Endogenous Tlr2 Activation And Brain Tumor Regression, James Curtin, Naiyou Liu, Marianela Candolfi, Weidong Xiong, Hikmat Assi, Kader Yagiz, Matthew Edwards, Kathrin Michelsen, Kurt Kroeger, Chunyan Liu, Akm Ghulam Muhammad, Mary Clark, Moshe Arditi, Begonya Comin-Anduix, Antoni Ribas, Pedro Lowenstein, Maria Castro

Articles

BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor that carries a 5-y survival rate of 5%. Attempts at eliciting a clinically relevant anti-GBM immune response in brain tumor patients have met with limited success, which is due to brain immune privilege, tumor immune evasion, and a paucity of dendritic cells (DCs) within the central nervous system. Herein we uncovered a novel pathway for the activation of an effective anti-GBM immune response mediated by high-mobility-group box 1 (HMGB1), an alarmin protein released from dying tumor cells, which acts as an endogenous ligand for Toll-like receptor 2 (TLR2) signaling ...


Treg Depletion Inhibits Efficacy Of Cancer Immunotherapy: Implications For Clinical Trials., James Curtin, Marianela Candolfi, Tamer Fakhouri, Chunyan Liu, Anderson Alden, Matthew Edwards, Pedro Lowenstein, Maria Castro Apr 2008

Treg Depletion Inhibits Efficacy Of Cancer Immunotherapy: Implications For Clinical Trials., James Curtin, Marianela Candolfi, Tamer Fakhouri, Chunyan Liu, Anderson Alden, Matthew Edwards, Pedro Lowenstein, Maria Castro

Articles

BACKGROUND: Regulatory T lymphocytes (Treg) infiltrate human glioblastoma (GBM); are involved in tumor progression and correlate with tumor grade. Transient elimination of Tregs using CD25 depleting antibodies (PC61) has been found to mediate GBM regression in preclinical models of brain tumors. Clinical trials that combine Treg depletion with tumor vaccination are underway to determine whether transient Treg depletion can enhance anti-tumor immune responses and improve long term survival in cancer patients. FINDINGS: Using a syngeneic intracrabial glioblastoma (GBM) mouse model we show that systemic depletion of Tregs 15 days after tumor implantation using PC61 resulted in a decrease in Tregs ...


Turning The Gene Tap Off; Implications Of Regulating Gene Expression For Cancer Therapeutics, James Curtin, Marianela Candolfi, Weidong Xiong, Pedro Lowenstein, Maria Castro Mar 2008

Turning The Gene Tap Off; Implications Of Regulating Gene Expression For Cancer Therapeutics, James Curtin, Marianela Candolfi, Weidong Xiong, Pedro Lowenstein, Maria Castro

Articles

Cancer poses a tremendous therapeutic challenge worldwide, highlighting the critical need for developing novel therapeutics. A promising cancer treatment modality is gene therapy, which is a form of molecular medicine designed to introduce into target cells genetic material with therapeutic intent. Anticancer gene therapy strategies currently used in preclinical models, and in some cases in the clinic, include proapoptotic genes, oncolytic/replicative vectors, conditional cytotoxic approaches, inhibition of angiogenesis, inhibition of growth factor signaling, inactivation of oncogenes, inhibition of tumor invasion and stimulation of the immune system. The translation of these novel therapeutic modalities from the preclinical setting to the ...


Regulated Expression Of Adenoviral Vectors-Based Gene Therapies: Therapeutic Expression Of Toxins And Immune-Modulators, James Curtin, Marianela Candolfi, Mariana Puntel, Weidong Xiong, Akm Ghulam Muhammad, Kurt Kroeger, Sonali Mondkar, Chunyan Liu, Niyati Bondale, Pedro Lowenstein, Maria Castro Jan 2008

Regulated Expression Of Adenoviral Vectors-Based Gene Therapies: Therapeutic Expression Of Toxins And Immune-Modulators, James Curtin, Marianela Candolfi, Mariana Puntel, Weidong Xiong, Akm Ghulam Muhammad, Kurt Kroeger, Sonali Mondkar, Chunyan Liu, Niyati Bondale, Pedro Lowenstein, Maria Castro

Articles

Regulatable promoter systems allow gene expression to be tightly controlled in vivo. This is highly desirable for the development of safe, efficacious adenoviral vectors that can be used to treat human diseases in the clinic. Ideally, regulatable cassettes should have minimal gene expression in the "OFF" state, and expression should quickly reach therapeutic levels in the "ON" state. In addition, the components of regulatable cassettes should be non-toxic at physiological concentrations and should not be immunogenic, especially when treating chronic illness that requires long-lasting gene expression. In this chapter, we will describe in detail protocols to develop and validate first ...


Novel Functions Of Acyl-Coa Thioesterases And Acyltransferases As Auxiliary Enzymes In Peroxisomal Lipid Metabolism., Mary Hunt, Stefan Alexson Jan 2008

Novel Functions Of Acyl-Coa Thioesterases And Acyltransferases As Auxiliary Enzymes In Peroxisomal Lipid Metabolism., Mary Hunt, Stefan Alexson

Articles

Peroxisomes are single membrane bound organelles present in almost all eukaryotic cells, and to date have been shown to contain approximately 60 identified enzymes involved in various metabolic pathways, including the oxidation of a variety of lipids. These lipids include very long-chain fatty acids, methyl branched fatty acids, prostaglandins, bile acid precursors, and xenobiotics that are either β-oxidized or α-oxidized in peroxisomes. The recent identification of several acyl-CoA thioesterases and acyltransferases in peroxisomes has revealed their various functions in acting as auxiliary enzymes in α- and β-oxidation in this organelle. To date, 9 functional acyl-CoA thioesterases and acyltransferases have been ...


The Nudix Hydrolase 7 Is An Acyl-Coa Diphosphatase Involved In Regulating Peroxisomal Coenzyme A Homeostasis., Sarah-Jayne Reilly, Veronica Tillander, Rob Ofman, Stefan Alexson, Mary Hunt Jan 2008

The Nudix Hydrolase 7 Is An Acyl-Coa Diphosphatase Involved In Regulating Peroxisomal Coenzyme A Homeostasis., Sarah-Jayne Reilly, Veronica Tillander, Rob Ofman, Stefan Alexson, Mary Hunt

Articles

Coenzyme A (CoASH) is an obligate cofactor for lipids undergoing β-oxidation in peroxisomes. Although the peroxisomal membrane appears to be impermeable to CoASH, peroxisomes contain their own pool of CoASH. It is believed that CoASH enters peroxisomes as acyl-CoAs, but it is not known how this pool is regulated. The mouse nudix hydrolase 7 (NUDT7α) was previously identified in peroxisomes as a CoAdiphosphatase, and therefore suggested to be involved in regulation of peroxisomal CoASH levels. Here we show that mouse NUDT7α mainly acts as an acyl-CoA diphosphatase, with highest activity towards medium chain acyl-CoAs, and much lower activity with CoASH ...


A Peroxisomal Acyltransferase In Mouse Identifies A Novel Pathway For Taurine Conjugation Of Fatty Acids., Sarah-Jayne Reilly, Eithne O'Shea, O'Byrne James, Stefan Alexson, Mary Hunt Jan 2007

A Peroxisomal Acyltransferase In Mouse Identifies A Novel Pathway For Taurine Conjugation Of Fatty Acids., Sarah-Jayne Reilly, Eithne O'Shea, O'Byrne James, Stefan Alexson, Mary Hunt

Articles

A wide variety of endogenous carboxylic acids and xenobiotics are conjugated with amino acids, before excretion in urine or bile. The conjugation of carboxylic acids and bile acids with taurine and glycine has been widely characterized and de-novo synthesized bile acids are conjugated to either glycine or taurine in peroxisomes. Peroxisomes are also involved in the oxidation of several other lipid molecules, such as very long chain acyl-CoAs, branched chain acyl-CoAs and prostaglandins. In this study we have now identified a novel peroxisomal enzyme called acyl-CoA:amino acid N-acyltransferase (ACNAT1). Recombinantly expressed ACNAT1 acts as an acyltransferase that efficiently conjugates ...


Peroxisomes Contain A Specific Phytanoly-Coa/Pristanoyl-Coa Thioesterase Acting As A Novel Auxiliary Enzyme In Alpha-And Beta-Oxidation Of Methyl-Branched Fatty Acids In Mouse, Maria Westin, Mary Hunt, Stefan Alexson Jan 2007

Peroxisomes Contain A Specific Phytanoly-Coa/Pristanoyl-Coa Thioesterase Acting As A Novel Auxiliary Enzyme In Alpha-And Beta-Oxidation Of Methyl-Branched Fatty Acids In Mouse, Maria Westin, Mary Hunt, Stefan Alexson

Articles

Phytanic acid and pristanic acid are derived from phytol, which enter the body via the diet. Phytanic acid contains a methyl group in position three and therefore cannot undergo b-oxidation directly, but instead must first undergo a-oxidation to pristanic acid, which then enters b-oxidation. Both these pathways occur in peroxisomes, and in this study we have identified a novel peroxisomal acyl-CoA thioesterase, named ACOT6, which we show is specifically involved in phytanic acid and pristanic acid metabolism. Sequence analysis of ACOT6 revealed a putative peroxisomal targeting signal at the C-terminal end, and cellular localization experiments verified it as a peroxisomal ...


Analysis Of The Mouse And Human Acyl-Coa Thioesterase (Acot) Gene Clusters Shows That Convergent, Functional Evolution Results In A Reduced Number Of Human Peroxisomal Acots., Mary Hunt, Anna Rautanen, Maria Westin, Thomas Svensson, Stefan Alexson Jan 2006

Analysis Of The Mouse And Human Acyl-Coa Thioesterase (Acot) Gene Clusters Shows That Convergent, Functional Evolution Results In A Reduced Number Of Human Peroxisomal Acots., Mary Hunt, Anna Rautanen, Maria Westin, Thomas Svensson, Stefan Alexson

Articles

The maintenance of cellular levels of free fatty acids and acyl-CoAs, the activated form of free fatty acids, is extremely important as imbalances in lipid metabolism have serious consequences for human health. Acyl-CoA thioesterases (ACOTs) hydrolyze acyl-CoAs to the free fatty acid and CoASH, and thereby have the potential to regulate intracellular levels of these compounds. We have previously identified and characterized a mouse ACOT gene cluster, comprised of six genes that apparently arose by gene duplications, encoding acyl- CoA thioesterases with localizations in cytosol (ACOT1), mitochondria (ACOT2) and peroxisomes (ACOT3-6). However, the corresponding human gene cluster contains only three ...


Regulatable Gene Expression Systems For Gene Therapy Applications: Progress And Future Challenges, Shyam Goverdhana, Mariana Puntel, Weidong Xiong, Jeffrey Zirger, Carlos Barcia, James Curtin, Eric Soffer, Sonali Mondkar, Gwendalyn King, Jinwei Hu, Marianela Candolfi, Diane Greengold, Pedro Lowenstein, Maria Castro Aug 2005

Regulatable Gene Expression Systems For Gene Therapy Applications: Progress And Future Challenges, Shyam Goverdhana, Mariana Puntel, Weidong Xiong, Jeffrey Zirger, Carlos Barcia, James Curtin, Eric Soffer, Sonali Mondkar, Gwendalyn King, Jinwei Hu, Marianela Candolfi, Diane Greengold, Pedro Lowenstein, Maria Castro

Articles

Gene therapy aims to revert diseased phenotypes by the use of both viral and nonviral gene delivery systems. Substantial progress has been made in making gene transfer vehicles more efficient, less toxic, and nonimmunogenic and in allowing long-term transgene expression. One of the key issues in successfully implementing gene therapies in the clinical setting is to be able to regulate gene expression very tightly and consistently as and when it is needed. The regulation ought to be achievable using a compound that should be nontoxic, be able to penetrate into the desired target tissue or organ, and have a half-life ...


A Revised Nomenclature For Mammalian Acyl-Coa Thioesterases/Hydrolases, Mary Hunt, Junji Yamada, Lois Maltais, Mathew Wright, Ernesto Podesta, Stefan Alexson Jun 2005

A Revised Nomenclature For Mammalian Acyl-Coa Thioesterases/Hydrolases, Mary Hunt, Junji Yamada, Lois Maltais, Mathew Wright, Ernesto Podesta, Stefan Alexson

Articles

Acyl-CoA thioesterases, also known as acyl-CoA hydrolases, are a group of enzymes that hydrolyze CoA esters such as acyl-CoAs (saturated, unsaturated, branched chain), bile acid-CoAs, CoA esters of prostaglandins etc, to the corresponding free acid and coenzyme A. There is however significant confusion regarding the nomenclature of these genes. In agreement with the HUGO Gene Nomenclature Committee (HGNC) and the Mouse Genomic Nomenclature Committee (MGNC), a revised nomenclature for mammalian acyl-CoA thioesterases/hydrolases has been suggested for the 12 member family. The family root symbol is ACOT, with human genes named ACOT1-12, and rat and mouse named Acot1-12. Several of ...


Identification Of Fatty Acid Oxidation Disorder Patients With Lowered Acyl-Coa Thioesterase Activity In Human Skin Fibroblasts, Mary Hunt, Jos Ruiter, Petra Mooyer, Carlo W T Van Roermond, Rob Ofman, Lodewig Ijlst, Ronald J A Wanders Jan 2005

Identification Of Fatty Acid Oxidation Disorder Patients With Lowered Acyl-Coa Thioesterase Activity In Human Skin Fibroblasts, Mary Hunt, Jos Ruiter, Petra Mooyer, Carlo W T Van Roermond, Rob Ofman, Lodewig Ijlst, Ronald J A Wanders

Articles

Background: Acyl-CoA thioesterases are enzymes that hydrolyze acyl-CoAs to the free fatty acid and coenzyme A (CoASH). These enzymes have been identified in several cellular compartments and are thought to regulate intracellular levels of acyl-CoAs, free fatty acids and CoASH. However, to date no patients deficient in acyl-CoA thioesterases have been identified. Design: Acyl-CoA thioesterase activity was measured in human skin fibroblasts. Western blot analysis was used to determine Type-II acyl-CoA thioesterase protein levels in patients. Results: Activity was found in human fibroblasts with all saturated acyl-CoAs from C4:0- to C18:0-CoA, with highest activity detected with lauroyl-CoA and ...


New Insights Into Bile Acid Amidation, Mary Hunt, Eithne O'Shea, Karianne Solaas, Bengt Kase, Stefan Alexson Jan 2005

New Insights Into Bile Acid Amidation, Mary Hunt, Eithne O'Shea, Karianne Solaas, Bengt Kase, Stefan Alexson

Articles

No abstract provided.