Advances in biomembranes and lipid self-assembly, 2019
Abstract Necroptosis is a form of regulated cell death that critically depends on the function of... more Abstract Necroptosis is a form of regulated cell death that critically depends on the function of Mixed Lineage Kinase Domain-Like Pseudokinase (MLKL). MLKL activation triggers plasma membrane permeabilization and other cellular processes aimed at preparing necroptotic cells to communicate with its neighbors and stimulate inflammation and immunogenicity. Membrane repair mechanisms play a key role in delaying necroptosis, by compensating the lethal effect of MLKL. Tuning the regulation of MLKL activities and counterbalancing machineries can define cell fate and the way the immune system is activated. Beside necroptosis, other forms of cell death are also notable for their impact on the plasma membrane and their role at engaging the immune system. Understanding the principles that govern plasma membrane reorganization is crucial to regulate their diverse immunological outcomes. Here we review current knowledge about the involvement of MLKL in mediating necroptosis and compare it with other lytic types of cell death.
Reaction of 1-bromobutane was investigated using Fenton reagent. This reagent is known to be a go... more Reaction of 1-bromobutane was investigated using Fenton reagent. This reagent is known to be a good oxidant for organic pollutants, which is composed of Fe2+ and H2O2. The reaction products that were identified were: 1-bromo-2-butanol, 1-butanoyl bromide, 1,3-dibromobutane, 1,4-dibromobutane, and 1,1,1-tribromobutane. This was verified by separating and analyzing the reaction mixture by GC/MS. Mechanisms were proposed for the formation of the products of the reaction of 1-bromobutane and Fenton reagent
Chicken meat consumption remains high in the Philippines, and consequently, annual chicken produc... more Chicken meat consumption remains high in the Philippines, and consequently, annual chicken production has risen steadily over the years. Although most of the chicken meat available in the market are sourced from factory farms, there has been growing popularity of free-range chicken production, largely driven by its perceived health benefits and sanitation concerns in factory farms, among others. In this work, we aimed at comparing the trace metal (copper, iron, lead, manganese, and zinc) content of free-range and factory-farmed broiler chicken meat that are being sold in Laguna, Philippines. The samples were subjected to acid digestion and analysis was done using atomic absorption spectrometry. Results showed an average concentration between 0.17 – 0.24 mg/kg, 2.22 – 2.34 mg/kg, 0.12 – 0.15 mg/kg, 0.95 – 1.32 mg/kg, and 1.81 – 1.96 mg/kg for copper, iron, lead, manganese, and zinc, respectively. Statistical analysis using one-way ANOVA and Tukey multiple comparison test (p < 0.05...
Marine organisms are a very good source of unique bioactive secondary metabolites, although they ... more Marine organisms are a very good source of unique bioactive secondary metabolites, although they have been comparatively underexplored relative to their terrestrial counterparts. Preliminary investigation of crude extracts from the fire coral Millepora dichotoma revealed that the hemolytic potential of the MeOH extract, at a concentration of 5 mg/mL, was significantly lower at less than 5% hemolysis while DCM extract at the same concentration resulted to almost 100% hemolysis. Furthermore, antimicrobial assay revealed that the MeOH extract (5 mg/mL) mildly inhibited the fungi T. mentagrophytes and resulted in the thinning of growth of S. aureus, while DCM extracts showed no detectable activity against these organisms. These results demonstrated that MeOH extracts of M. dichotoma, without showing hemolytic side effects, could be further analysed for potential use against T. mentagrophytes and S. aureus infections.
Chemical investigation of the dichloromethane extract of the fire coral, Millepora dichotoma yiel... more Chemical investigation of the dichloromethane extract of the fire coral, Millepora dichotoma yielded β-sitosterol (1), triacylglycerols (2), and wax esters (3). The structures of 1-3 were identified by comparison of their NMR data with literature data.
Cholesterol-dependent cytolysins (CDCs) are proteinaceous toxins secreted as monomers by some Gra... more Cholesterol-dependent cytolysins (CDCs) are proteinaceous toxins secreted as monomers by some Gram-positive and Gram-negative bacteria that contribute to their pathogenicity. These toxins bind to either cholesterol or human CD59, leading to massive structural changes, toxin oligomerization, formation of very large pores, and ultimately cell death, making these proteins promising targets for inhibition. Myricetin, and its related flavonoids, have been previously identified as a candidate small molecule inhibitor of specific CDCs such as listeriolysin O (LLO) and suilysin (SLY), interfering with their oligomerization. In this work, molecular docking was performed to assess the interaction of myricetin with other CDCs whose crystal structures are already known. Results indicated that although myricetin bound to the hitherto identified cavity in domain 4 (D4), much more efficient and stable binding was obtained in sites along the interfacial regions of domains 1 – 3 (D1 – D3). This was ...
Zeitschrift fur Naturforschung. C, Journal of biosciences, Jan 9, 2016
Amphidinol 3 (AM3) and theonellamide A (TNM-A) are potent antifungal compounds produced by the di... more Amphidinol 3 (AM3) and theonellamide A (TNM-A) are potent antifungal compounds produced by the dinoflagellate Amphidinium klebsii and the sponge Theonella spp., respectively. Both of these metabolites have been demonstrated to interact with membrane lipids ultimately resulting in a compromised bilayer integrity. In this report, the activity of AM3 and TNM-A in ternary lipid mixtures composed of 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (POPC):brain sphingomyelin:cholesterol at a mole ratio of 1:1:1 or 3:1:1 exhibiting lipid rafts coexistence is presented. It was found that AM3 has a more extensive membrane permeabilizing activity compared with TNM-A in these membrane mimics, which was almost complete at 15 μM. The extent of their activity nevertheless is similar to the previously reported binary system of POPC and cholesterol, suggesting that phase separation has neither beneficial nor detrimental effects in their ability to disrupt the lipid bilayer.
SummaryFerroptosis is an iron-dependent form of regulated necrosis associated with lipid peroxida... more SummaryFerroptosis is an iron-dependent form of regulated necrosis associated with lipid peroxidation. Despite its key role in the inflammatory outcome of ferroptosis, little is known about the molecular events leading to the disruption of the plasma membrane during this type of cell death. Here we show that a sustained increase in cytosolic Ca2+ is a hallmark of ferroptosis that precedes complete bursting of the cell. We report that plasma membrane damage leading to ferroptosis is associated with membrane nanopores of few nanometers in radius and that ferroptosis, but not lipid peroxidation, can be delayed by osmoprotectants. Importantly, Ca2+ fluxes during ferroptosis correlate with the activation of ESCRT-III-mediated membrane repair, which counterbalances the kinetics of cell death and modulates the inflammatory signature of ferroptosis. Our findings with ferroptosis provide a unifying concept that sustained high levels of cytosolic Ca2+ prior to plasma membrane disruption are a...
Theonellamides (TNMs) are antifungal and cytotoxic bicyclic dodecapeptides derived from the marin... more Theonellamides (TNMs) are antifungal and cytotoxic bicyclic dodecapeptides derived from the marine sponge Theonella sp. These peptides specifically bind to 3β-hydroxysterols, resulting in 1,3-β-d-glucan overproduction and membrane damage in yeasts. The inclusion of cholesterol or ergosterol in phosphatidylcholine membranes significantly enhanced the membrane affinity of theonellamide A (TNM-A) because of its direct interaction with 3β-hydroxyl groups of sterols. To better understand TNM-induced membrane alterations, we investigated the effects of TNM-A on liposome morphology. (31)P nuclear magnetic resonance (NMR) and dynamic light scattering (DLS) measurements revealed that the premixing of TNM-A with lipids induced smaller vesicle formation. When giant unilamellar vesicles were incubated with exogenously added TNM-A, confocal micrographs showed dynamic changes in membrane morphology, which were more frequently observed in cholesterol-containing than sterol-free liposomes. In conju...
Advances in biomembranes and lipid self-assembly, 2019
Abstract Necroptosis is a form of regulated cell death that critically depends on the function of... more Abstract Necroptosis is a form of regulated cell death that critically depends on the function of Mixed Lineage Kinase Domain-Like Pseudokinase (MLKL). MLKL activation triggers plasma membrane permeabilization and other cellular processes aimed at preparing necroptotic cells to communicate with its neighbors and stimulate inflammation and immunogenicity. Membrane repair mechanisms play a key role in delaying necroptosis, by compensating the lethal effect of MLKL. Tuning the regulation of MLKL activities and counterbalancing machineries can define cell fate and the way the immune system is activated. Beside necroptosis, other forms of cell death are also notable for their impact on the plasma membrane and their role at engaging the immune system. Understanding the principles that govern plasma membrane reorganization is crucial to regulate their diverse immunological outcomes. Here we review current knowledge about the involvement of MLKL in mediating necroptosis and compare it with other lytic types of cell death.
Reaction of 1-bromobutane was investigated using Fenton reagent. This reagent is known to be a go... more Reaction of 1-bromobutane was investigated using Fenton reagent. This reagent is known to be a good oxidant for organic pollutants, which is composed of Fe2+ and H2O2. The reaction products that were identified were: 1-bromo-2-butanol, 1-butanoyl bromide, 1,3-dibromobutane, 1,4-dibromobutane, and 1,1,1-tribromobutane. This was verified by separating and analyzing the reaction mixture by GC/MS. Mechanisms were proposed for the formation of the products of the reaction of 1-bromobutane and Fenton reagent
Chicken meat consumption remains high in the Philippines, and consequently, annual chicken produc... more Chicken meat consumption remains high in the Philippines, and consequently, annual chicken production has risen steadily over the years. Although most of the chicken meat available in the market are sourced from factory farms, there has been growing popularity of free-range chicken production, largely driven by its perceived health benefits and sanitation concerns in factory farms, among others. In this work, we aimed at comparing the trace metal (copper, iron, lead, manganese, and zinc) content of free-range and factory-farmed broiler chicken meat that are being sold in Laguna, Philippines. The samples were subjected to acid digestion and analysis was done using atomic absorption spectrometry. Results showed an average concentration between 0.17 – 0.24 mg/kg, 2.22 – 2.34 mg/kg, 0.12 – 0.15 mg/kg, 0.95 – 1.32 mg/kg, and 1.81 – 1.96 mg/kg for copper, iron, lead, manganese, and zinc, respectively. Statistical analysis using one-way ANOVA and Tukey multiple comparison test (p < 0.05...
Marine organisms are a very good source of unique bioactive secondary metabolites, although they ... more Marine organisms are a very good source of unique bioactive secondary metabolites, although they have been comparatively underexplored relative to their terrestrial counterparts. Preliminary investigation of crude extracts from the fire coral Millepora dichotoma revealed that the hemolytic potential of the MeOH extract, at a concentration of 5 mg/mL, was significantly lower at less than 5% hemolysis while DCM extract at the same concentration resulted to almost 100% hemolysis. Furthermore, antimicrobial assay revealed that the MeOH extract (5 mg/mL) mildly inhibited the fungi T. mentagrophytes and resulted in the thinning of growth of S. aureus, while DCM extracts showed no detectable activity against these organisms. These results demonstrated that MeOH extracts of M. dichotoma, without showing hemolytic side effects, could be further analysed for potential use against T. mentagrophytes and S. aureus infections.
Chemical investigation of the dichloromethane extract of the fire coral, Millepora dichotoma yiel... more Chemical investigation of the dichloromethane extract of the fire coral, Millepora dichotoma yielded β-sitosterol (1), triacylglycerols (2), and wax esters (3). The structures of 1-3 were identified by comparison of their NMR data with literature data.
Cholesterol-dependent cytolysins (CDCs) are proteinaceous toxins secreted as monomers by some Gra... more Cholesterol-dependent cytolysins (CDCs) are proteinaceous toxins secreted as monomers by some Gram-positive and Gram-negative bacteria that contribute to their pathogenicity. These toxins bind to either cholesterol or human CD59, leading to massive structural changes, toxin oligomerization, formation of very large pores, and ultimately cell death, making these proteins promising targets for inhibition. Myricetin, and its related flavonoids, have been previously identified as a candidate small molecule inhibitor of specific CDCs such as listeriolysin O (LLO) and suilysin (SLY), interfering with their oligomerization. In this work, molecular docking was performed to assess the interaction of myricetin with other CDCs whose crystal structures are already known. Results indicated that although myricetin bound to the hitherto identified cavity in domain 4 (D4), much more efficient and stable binding was obtained in sites along the interfacial regions of domains 1 – 3 (D1 – D3). This was ...
Zeitschrift fur Naturforschung. C, Journal of biosciences, Jan 9, 2016
Amphidinol 3 (AM3) and theonellamide A (TNM-A) are potent antifungal compounds produced by the di... more Amphidinol 3 (AM3) and theonellamide A (TNM-A) are potent antifungal compounds produced by the dinoflagellate Amphidinium klebsii and the sponge Theonella spp., respectively. Both of these metabolites have been demonstrated to interact with membrane lipids ultimately resulting in a compromised bilayer integrity. In this report, the activity of AM3 and TNM-A in ternary lipid mixtures composed of 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (POPC):brain sphingomyelin:cholesterol at a mole ratio of 1:1:1 or 3:1:1 exhibiting lipid rafts coexistence is presented. It was found that AM3 has a more extensive membrane permeabilizing activity compared with TNM-A in these membrane mimics, which was almost complete at 15 μM. The extent of their activity nevertheless is similar to the previously reported binary system of POPC and cholesterol, suggesting that phase separation has neither beneficial nor detrimental effects in their ability to disrupt the lipid bilayer.
SummaryFerroptosis is an iron-dependent form of regulated necrosis associated with lipid peroxida... more SummaryFerroptosis is an iron-dependent form of regulated necrosis associated with lipid peroxidation. Despite its key role in the inflammatory outcome of ferroptosis, little is known about the molecular events leading to the disruption of the plasma membrane during this type of cell death. Here we show that a sustained increase in cytosolic Ca2+ is a hallmark of ferroptosis that precedes complete bursting of the cell. We report that plasma membrane damage leading to ferroptosis is associated with membrane nanopores of few nanometers in radius and that ferroptosis, but not lipid peroxidation, can be delayed by osmoprotectants. Importantly, Ca2+ fluxes during ferroptosis correlate with the activation of ESCRT-III-mediated membrane repair, which counterbalances the kinetics of cell death and modulates the inflammatory signature of ferroptosis. Our findings with ferroptosis provide a unifying concept that sustained high levels of cytosolic Ca2+ prior to plasma membrane disruption are a...
Theonellamides (TNMs) are antifungal and cytotoxic bicyclic dodecapeptides derived from the marin... more Theonellamides (TNMs) are antifungal and cytotoxic bicyclic dodecapeptides derived from the marine sponge Theonella sp. These peptides specifically bind to 3β-hydroxysterols, resulting in 1,3-β-d-glucan overproduction and membrane damage in yeasts. The inclusion of cholesterol or ergosterol in phosphatidylcholine membranes significantly enhanced the membrane affinity of theonellamide A (TNM-A) because of its direct interaction with 3β-hydroxyl groups of sterols. To better understand TNM-induced membrane alterations, we investigated the effects of TNM-A on liposome morphology. (31)P nuclear magnetic resonance (NMR) and dynamic light scattering (DLS) measurements revealed that the premixing of TNM-A with lipids induced smaller vesicle formation. When giant unilamellar vesicles were incubated with exogenously added TNM-A, confocal micrographs showed dynamic changes in membrane morphology, which were more frequently observed in cholesterol-containing than sterol-free liposomes. In conju...
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