-
International Journal of Molecular... Dec 2021ATP-binding cassette (ABC) transporters are conserved in all kingdoms of life, where they transport substrates against a concentration gradient across membranes. Some...
ATP-binding cassette (ABC) transporters are conserved in all kingdoms of life, where they transport substrates against a concentration gradient across membranes. Some ABC transporters are known to cause multidrug resistances in humans and are able to transport chemotherapeutics across cellular membranes. Similarly, BmrA, the ABC transporter of is involved in excretion of certain antibiotics out of bacterial cells. Screening of extract libraries isolated from fungi revealed that the C14 fatty acid myristic acid has an inhibitory effect on the BmrA ATPase as well as the transport activity. Thus, a natural membrane constituent inhibits the BmrA activity, a finding with physiological consequences as to the activity and regulation of ABC transporter activities in biological membranes.
Topics: ATP-Binding Cassette Transporters; Adenosine Triphosphatases; Bacillus subtilis; Bacterial Proteins; Drug Discovery; Myristic Acid
PubMed: 34948362
DOI: 10.3390/ijms222413565 -
Journal of Oleo Science Sep 2021Fatty acids and their derivatives are interesting cosmetic ingredients because they show the selective antibacterial activity against Staphylococcus aureus (S. aureus)....
Fatty acids and their derivatives are interesting cosmetic ingredients because they show the selective antibacterial activity against Staphylococcus aureus (S. aureus). However, the antibacterial activity in mixed systems containing several active ingredients is unclear because previous studies focused antibacterial systems containing one kind of fatty acid. In the present study, the minimal inhibitory concentration (MIC) and the fractional inhibitory concentration (FIC) were evaluated for myristic acid/lauric acid, myristic acid/palmitoleic acid, and myristic acid/lactic acid mixed systems to show the effect of the coexisting components on the selective antibacterial activity of myristic acid. In the myristic acid/palmitoleic acid mixed system, the antibacterial activity against S. aureus was enhanced by additive effect, whereas the antibacterial activity was not observed against S. epidermidis. On the other hand, the myristic acid/lauric acid mixed system showed antibacterial activity against S. epidermidis: Lauric acid impaired the selectivity of antibacterial activity of myristic acid. These results suggest that the selective activity of myristic acid varies with the additives. The present findings are useful for designing formulations of cosmetics and body cleansers containing myristic acid.
Topics: Cosmetics; Drug Interactions; Drug Resistance, Bacterial; Fatty Acids, Monounsaturated; Lauric Acids; Myristic Acid; Staphylococcus aureus; Staphylococcus epidermidis
PubMed: 34373405
DOI: 10.5650/jos.ess21090 -
The Journal of Biological Chemistry Aug 2005Dietary free fatty acids have been reported to have various effects on the endothelium including the generation of nitric oxide. The goal of the current study was to...
Dietary free fatty acids have been reported to have various effects on the endothelium including the generation of nitric oxide. The goal of the current study was to determine the mechanism whereby free fatty acid causes an increase in nitric oxide synthesis. The specific hypothesis tested was that free fatty acid association with CD36, a class B scavenger receptor, induces the activation of endothelial nitric-oxide synthase (eNOS). A human microvascular endothelial cell line and a transfected Chinese hamster ovary cell system were used to determine which free fatty acids stimulate eNOS. Surprisingly, only myristic acid, and to a lesser extent palmitic acid, stimulated eNOS. The stimulation of eNOS was dose- and time-dependent. Competition experiments with other free fatty acids and with a CD36-blocking antibody demonstrated that the effects of myristic acid on eNOS required association with CD36. Further mechanistic studies demonstrated that the effects of myristic acid on eNOS function were not dependent on PI 3-kinase, Akt kinase, or calcium. Pharmacological studies and dominant negative constructs were used to demonstrate that myristic acid/CD36 stimulation of eNOS activity was dependent on the activation of AMP kinase. These data demonstrate an unexpected link among myristic acid, CD36, AMP kinase, and eNOS activity.
Topics: Adenylate Kinase; Animals; CD36 Antigens; CHO Cells; Cells, Cultured; Cricetinae; Humans; Myristic Acid; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Phosphorylation
PubMed: 15970594
DOI: 10.1074/jbc.M501238200 -
BMC Complementary and Alternative... Jun 2019Embryonic neural stem cells (eNSCs) are immature precursors of the central nervous system (CNS), with self-renewal and multipotential differentiation capacities. These...
Alyssum homolocarpum seed oil (AHSO), containing natural alpha linolenic acid, stearic acid, myristic acid and β-sitosterol, increases proliferation and differentiation of neural stem cells in vitro.
BACKGROUND
Embryonic neural stem cells (eNSCs) are immature precursors of the central nervous system (CNS), with self-renewal and multipotential differentiation capacities. These are regulated by endogenous and exogenous factors such as alpha-linolenic acid (ALA), a plant-based essential omega-3 polyunsaturated fatty acid.
METHODS
In this study, we investigated the effects of various concentrations of Alyssum homolocarpum seed oil (AHSO), containing natural ALA, stearic acid (SA), myristic acid (MA), and β-sitosterol, on proliferation and differentiation of eNSCs, in comparison to controls and to synthetic pure ALA.
RESULTS
Treatment with natural AHSO (25 to 75 μM), similar to synthetic ALA, caused a significant ~ 2-fold increase in eNCSs viability, in comparison to controls. To confirm this proliferative activity, treatment of NSCs with 50 or 75 μM AHSO resulted in a significant increase in mRNA levels of notch1, hes-1 and Ki-67and NICD protein expression, in comparison to controls. Moreover, AHSO administration significantly increased the differentiation of eNSCs toward astrocytes (GFAP+) and oligodendrocytes (MBP+) in a dose dependent manner and was more potent than ALA, at similar concentrations, in comparison to controls. Indeed, only high concentrations of 100 μM AHSO, but not ALA, caused a significant increase in the frequency of neurons (β-III Tubulin+).
CONCLUSION
Our data demonstrated that AHSO, a rich source of ALA containing also other beneficial fatty acids, increased the proliferation and stimulated the differentiation of eNSCs. We suggest that AHSO's effects are caused by β-sitosterol, SA and MA, present within this oil. AHSO could be used in diet to prevent neurodevelopmental syndromes, cognitive decline during aging, and various psychiatric disorders.
Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Brassicaceae; Cell Differentiation; Cell Proliferation; Drug Evaluation, Preclinical; Ki-67 Antigen; Mice; Myristic Acid; Neural Stem Cells; Neurogenesis; Plant Oils; Seeds; Sitosterols; Stearic Acids; alpha-Linolenic Acid
PubMed: 31159797
DOI: 10.1186/s12906-019-2518-4 -
The American Journal of Clinical... Feb 2010The use of serum fatty acid biomarkers in nutritional epidemiology is increasingly common; however, there is an absence of scientific evidence to substantiate whether...
The serum fatty acids myristic acid and linoleic acid are better predictors of serum cholesterol concentrations when measured as molecular percentages rather than as absolute concentrations.
BACKGROUND
The use of serum fatty acid biomarkers in nutritional epidemiology is increasingly common; however, there is an absence of scientific evidence to substantiate whether the measurement of fatty acids as molecular percentages (which is the conventional approach) or as absolute concentrations is more informative.
OBJECTIVE
To advance understanding about this fundamental concept, we examined the ability of serum myristic acid and linoleic acid, expressed as molecular percentages or as concentrations, to predict dietary fat and serum cholesterol concentrations.
DESIGN
A cross-sectional analysis of a population-based survey of New Zealand adults (n = 2732) was undertaken. The association of myristic and linoleic acids in serum cholesterol ester and phospholipid with dietary fat or serum cholesterol was assessed.
RESULTS
Intake of saturated fat, dairy fat, and polyunsaturated fat was predicted similarly with the use of both units of measurement. After adjustment for confounders, mean total cholesterol decreased by 0.18 mmol/L from the lowest to the highest quintile of serum cholesteryl-linoleate as a molecular percentage (P = 0.027). In contrast, mean total cholesterol increased by 1.09 mmol/L from the lowest to the highest quintile of serum cholesteryl-linoleate concentration (P < 0.001). The molecular percentage and concentration of serum cholesteryl-myristate were positively associated with total cholesterol (P < 0.001). Results for serum phospholipid fatty acids were similar.
CONCLUSION
Serum myristic acid and linoleic acid measured as molecular percentages, but not as concentrations, predict serum total cholesterol in a manner that distinguishes between the differential cholesterolemic effects of dietary saturated and polyunsaturated fats.
Topics: Adolescent; Adult; Aged; Cholesterol; Cross-Sectional Studies; Dietary Fats; Humans; Linear Models; Linoleic Acid; Middle Aged; Myristic Acid; New Zealand; Young Adult
PubMed: 19955401
DOI: 10.3945/ajcn.2009.28159 -
The Journal of Nutrition Oct 2020
Topics: Apolipoprotein C-III; Humans; Myristic Acid; Triglycerides
PubMed: 32805056
DOI: 10.1093/jn/nxaa228 -
Methods in Molecular Biology (Clifton,... 2019The use of synthetically synthesized azide and alkyne fatty acid analogs coupled with bioorthogonal Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction-based...
The use of synthetically synthesized azide and alkyne fatty acid analogs coupled with bioorthogonal Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction-based detection methods to study protein S-acylation reactions has replaced the traditional method of using in vivo metabolic radiolabeling with tritiated palmitic acid and has greatly facilitated our understanding of this essential cellular process. Here, we describe the chemical synthesis of myristic (C:14), palmitic (C16:0), and stearic (C18:0) acid-azide probes and detail how they may be utilized as chemical reporters for the analysis of S-acylation of exogenously expressed proteins in cells.
Topics: Acylation; Cycloaddition Reaction; HEK293 Cells; Humans; Myristic Acid; Palmitic Acid; Protein S; Stearic Acids
PubMed: 31152392
DOI: 10.1007/978-1-4939-9532-5_2 -
Nature Communications Feb 2018Potent antiretroviral activities and a barrier to viral resistance characterize the human immunodeficiency virus type one (HIV-1) integrase strand transfer inhibitor...
Potent antiretroviral activities and a barrier to viral resistance characterize the human immunodeficiency virus type one (HIV-1) integrase strand transfer inhibitor dolutegravir (DTG). Herein, a long-acting parenteral DTG was created through chemical modification to improve treatment outcomes. A hydrophobic and lipophilic modified DTG prodrug is encapsulated into poloxamer nanoformulations (NMDTG) and characterized by size, shape, polydispersity, and stability. Retained intracytoplasmic NMDTG particles release drug from macrophages and attenuate viral replication and spread of virus to CD4+ T cells. Pharmacokinetic tests in Balb/cJ mice show blood DTG levels at, or above, its inhibitory concentration of 64 ng/mL for 56 days, and tissue DTG levels for 28 days. NMDTG protects humanized mice from parenteral challenge of the HIV-1 strain for two weeks. These results are a first step towards producing a long-acting DTG for human use by affecting drug apparent half-life, cell and tissue drug penetration, and antiretroviral potency.
Topics: Animals; Drug Delivery Systems; Drug Evaluation, Preclinical; HIV Infections; HIV Integrase Inhibitors; Heterocyclic Compounds, 3-Ring; Humans; Male; Mice, Inbred BALB C; Myristic Acid; Nanoparticles; Oxazines; Piperazines; Pyridones
PubMed: 29402886
DOI: 10.1038/s41467-018-02885-x -
Parasitology Jan 2014Infections caused by protozoan parasites are among the most widespread and intractable transmissible diseases affecting the developing world, with malaria and... (Review)
Review
Infections caused by protozoan parasites are among the most widespread and intractable transmissible diseases affecting the developing world, with malaria and leishmaniasis being the most costly in terms of morbidity and mortality. Although new drugs are urgently required against both diseases in the face of ever-rising resistance to frontline therapies, very few candidates passing through development pipelines possess a known and novel mode of action. Set in the context of drugs currently in use and under development, we present the evidence for N-myristoyltransferase (NMT), an enzyme that N-terminally lipidates a wide range of specific target proteins through post-translational modification, as a potential drug target in malaria and the leishmaniases. We discuss the limitations of current knowledge regarding the downstream targets of this enzyme in protozoa, and our recent progress towards potent cell-active NMT inhibitors against the most clinically-relevant species of parasite. Finally, we outline the next steps required in terms of both tools to understand N-myristoylation in protozoan parasites, and the generation of potential development candidates based on the output of our recently-reported high-throughput screens.
Topics: Acyltransferases; Antiprotozoal Agents; Drug Discovery; Enzyme Inhibitors; High-Throughput Screening Assays; Humans; Leishmaniasis; Malaria; Models, Molecular; Molecular Targeted Therapy; Myristic Acid; Protein Processing, Post-Translational; Protozoan Proteins; Structure-Activity Relationship; Substrate Specificity
PubMed: 23611109
DOI: 10.1017/S0031182013000450 -
Molecules (Basel, Switzerland) Aug 2022This work developd nanomaterials formulated from annatto seed oily extract (ASE), myristic acid (tetradecanoic acid), and their fatty acid esters. The annatto seed oily...
This work developd nanomaterials formulated from annatto seed oily extract (ASE), myristic acid (tetradecanoic acid), and their fatty acid esters. The annatto seed oily extract was obtained using only soybean oil (ASE + SO) and Brazil nut oil (ASE + BNO). The UV/VIS analysis of the oily extracts showed three characteristic peaks of the bixin molecule at 430, 456 and 486 nm. The lipid nanoparticles obtained using myristic acid and ASE + BNO or only BNO showed better results than the oil soybean extract, i.e., the particle size was <200 nm, PDI value was in the range of 0.2−0.3, and had no visual physical instability as they kept stable for 28 days at 4 °C. Lipid nanoemulsions were also produced with esters of myristic acid and ASE + BNO. These fatty acid esters significantly influenced the particle size of nanoemulsions. For instance, methyl tetradecanoate led to the smallest particle size nanoemulsions (124 nm), homogeneous size distribution, and high physical stability under 4 and 32 °C for 28 days. This work demonstrates that the chemical composition of vegetable oils and myristic acid esters, the storage temperature, the chain length of fatty acid esters (FAE), and their use as co-lipids improve the physical stability of lipid nanoemulsions and nanoparticles from annatto seed oily extract.
Topics: Bixaceae; Carotenoids; Fatty Acids; Liposomes; Myristic Acid; Nanoparticles; Plant Extracts; Seeds
PubMed: 36014427
DOI: 10.3390/molecules27165187