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Molecules (Basel, Switzerland) Sep 2017APOBEC3G is a member of the human cytidine deaminase family that restricts Vif-deficient viruses by being packaged with progeny virions and inducing the G to A mutation...
APOBEC3G is a member of the human cytidine deaminase family that restricts Vif-deficient viruses by being packaged with progeny virions and inducing the G to A mutation during the synthesis of HIV-1 viral DNA when the progeny virus infects new cells. HIV-1 Vif protein resists the activity of A3G by mediating A3G degradation. Phorbol esters are plant-derived organic compounds belonging to the tigliane family of diterpenes and could activate the PKC pathway. In this study, we identified an inhibitor 12--tricosanoylphorbol-20-acetate (hop-8), a novel ester of phorbol which was isolated from of the family Euphorbiaceae, that inhibited the replication of wild-type HIV-1 and HIV-2 strains and drug-resistant strains broadly both in C8166 cells and PBMCs with low cytotoxicity and the EC values ranged from 0.106 μM to 7.987 μM. One of the main mechanisms of hop-8 is to stimulate A3G expressing in HIV-1 producing cells and upregulate the A3G level in progeny virions, which results in reducing the infectivity of the progeny virus. This novel mechanism of hop-8 inhibition of HIV replication might represents a promising approach for developing new therapeutics for HIV infection.
Topics: APOBEC-3G Deaminase; Anti-HIV Agents; Cell Line; DNA, Viral; Euphorbiaceae; Gene Expression Regulation; HIV-1; HIV-2; Host-Pathogen Interactions; Humans; Leukocytes, Mononuclear; Mutation; Phorbol Esters; Plant Extracts; Primary Cell Culture; Protein Kinase C; Signal Transduction; T-Lymphocytes; Virion; Virus Replication; vif Gene Products, Human Immunodeficiency Virus
PubMed: 28885587
DOI: 10.3390/molecules22091498 -
Veterinary Research Communications Sep 2023Physic nut Jatropha curcas cake/meal obtained after oil extraction has a high protein content, however, the presence of antinutrients (trypsin inhibitor, lectin and...
Physic nut Jatropha curcas cake/meal obtained after oil extraction has a high protein content, however, the presence of antinutrients (trypsin inhibitor, lectin and phytate) and toxic compounds (phorbol esters) limit their use as an alternative feedstuff. Thus, the detoxification process in cake/meal is necessary to allow their inclusion in fish diets. The present study aimed to evaluate the effects of solvent and extrusion-treated jatropha cake (SETJC) in Nile tilapia (Oreochromis niloticus) diets on growth, body composition, nutrient utilization, metabolic and hematological responses, and digestibility of experimental diets. Five experimental diets were formulated to be isonitrogenous (28.50% digestible protein) and isoenergetic (13.39 MJ/kg digestible energy) with graded levels of SETJC (0, 3, 6, 9, and 12%). The experimental design was completely randomized with five treatments and four replicates. The detoxification treatments reduced the phorbol esters (PE) of jatropha cake by 96% (0.58 mg/g of PE before and 0.023 mg/g of PE after treatments). Increased levels of SETJC depressed growth, feed efficiency, and protein digestibility. A similar trend was observed for hematological and biochemistry parameters. Aspartate and alanine aminotransferase, as well as phosphorus and magnesium concentrations in the fillets, increased at the highest levels of SETJC. Thus, the data of the present study suggests that the residual content, different structural forms of phorbol ester and its biological activity, as well as some antinutritional factors, can influence negatively the growth, metabolism and digestibility of experimental diets for Nile tilapia.
Topics: Animals; Cichlids; Jatropha; Animal Feed; Solvents; Diet; Phorbol Esters; Seeds
PubMed: 36729277
DOI: 10.1007/s11259-023-10076-3 -
Biochemical and Biophysical Research... Jan 2018Lysophosphatidic acid (LPA) signaling through six subtypes of LPA receptors (LPA to LPA) regulates a variety of biological responses in cancer cells. The aim of our...
Lysophosphatidic acid (LPA) signaling through six subtypes of LPA receptors (LPA to LPA) regulates a variety of biological responses in cancer cells. The aim of our study was to evaluate an involvement of LPA receptors in the activation of cell motility by phorbol ester and anticancer drug treatments in melanoma A375 cells. Cells were treated with 12-O-tetradecanoylphorbol- 13-acetate (TPA) and phorbol-12,13-dibutyrate (PDBu) for 3 days. The cell motile activity of TPA treated cells was significantly higher than that of PDBu treated cells, correlating with LPAR5 expression levels. LPA knockdown suppressed the high cell motile activity induced by TPA. To assess whether the cell motile activity of A375 cells is stimulated through LPA induced by anticancer drugs, the long-term cisplatin (CDDP) and dacarbazine (DTIC) treated cells were generated from A375 cells (A375-CDDP and A375-DTIC cells, respectively). The expression levels of LPA receptor genes were changed in A375-CDDP and A375-DTIC cells. In particular, CDDP and DTIC treatment markedly elevated LPAR5 expressions. The cell motile activities of A375-CDDP and A375-DTIC cells were significantly higher than that of untreated cells. These results suggest that the cell motile activity is regulated through the induction of LPA by phorbol ester and anticancer drug treatments in A375 cells.
Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Movement; Cell Proliferation; Dose-Response Relationship, Drug; Humans; Melanoma; Phorbol Esters; Receptors, Lysophosphatidic Acid; Skin Neoplasms
PubMed: 29309788
DOI: 10.1016/j.bbrc.2018.01.030 -
Journal of Biomolecular Structure &... 2022Munc13-1 is a presynaptic active zone protein that plays a critical role in priming the synaptic vesicle and releasing neurotransmitters in the brain. Munc13-1 acts as a...
Munc13-1 is a presynaptic active zone protein that plays a critical role in priming the synaptic vesicle and releasing neurotransmitters in the brain. Munc13-1 acts as a scaffold and is activated when diacylglycerol (DAG)/phorbol ester binds to its C1 domain in the plasma membrane. Our previous studies showed that bryostatin 1 activated the Munc13-1, but resveratrol inhibited the phorbol ester-induced Munc13-1 activity. To gain structural insights into the binding of the ligand into Munc13-1 C1 in the membrane, we conducted 1.0 μs molecular dynamics (MD) simulation on Munc13-1 C1-ligand-lipid ternary system using phorbol 13-acetate, bryostatin 1 and resveratrol as ligands. Munc13-1 C1 shows higher conformational stability and less mobility along membrane with phorbol 13-acetate and bryostatin 1 than with resveratrol. Bryostatin 1 and phorbol ester remained in the protein active site, but resveratrol moved out of Munc13-1 C1 during the MD simulation. While bryostatin 1-bound Munc13-1 C1 showed two different positioning in the membrane, phorbol 13-acetate and resveratrol-bound Munc13-1 C1 only showed one positioning. Phorbol 13-acetate formed hydrogen bond with Ala-574 and Gly-589. Bryostatin 1 had more hydrogen bonds with Trp-588 and Arg-592 than with other residues. Resveratrol formed hydrogen bond with Ile-590. This study suggests that different ligands control Munc13-1 C1's mobility and positioning in the membrane differently. Ligand also has a critical role in the interaction between Munc13-1 C1 and lipid membrane. Our results provide structural basis of the pharmacological activity of the ligands and highlight the importance of membrane in Munc13-1 activity.Communicated by Ramaswamy H. Sarma.
Topics: Molecular Dynamics Simulation; Ligands; Resveratrol; Phorbol Esters; Lipids
PubMed: 34779746
DOI: 10.1080/07391102.2021.2001375 -
Molecular Systems Biology Mar 2017To monitor transcriptional regulation in human cells, rapid changes in enhancer and promoter activity must be captured with high sensitivity and temporal resolution....
To monitor transcriptional regulation in human cells, rapid changes in enhancer and promoter activity must be captured with high sensitivity and temporal resolution. Here, we show that the recently established protocol TT-seq ("transient transcriptome sequencing") can monitor rapid changes in transcription from enhancers and promoters during the immediate response of T cells to ionomycin and phorbol 12-myristate 13-acetate (PMA). TT-seq maps eRNAs and mRNAs every 5 min after T-cell stimulation with high sensitivity and identifies many new primary response genes. TT-seq reveals that the synthesis of 1,601 eRNAs and 650 mRNAs changes significantly within only 15 min after stimulation, when standard RNA-seq does not detect differentially expressed genes. Transcription of enhancers that are primed for activation by nucleosome depletion can occur immediately and simultaneously with transcription of target gene promoters. Our results indicate that enhancer transcription is a good proxy for enhancer regulatory activity in target gene activation, and establish TT-seq as a tool for monitoring the dynamics of enhancer landscapes and transcription programs during cellular responses and differentiation.
Topics: Base Pairing; Enhancer Elements, Genetic; Gene Expression Profiling; Gene Expression Regulation; Humans; Ionomycin; Jurkat Cells; RNA; Sequence Analysis, RNA; T-Lymphocytes; Tetradecanoylphorbol Acetate; Transcription, Genetic; Transcriptional Activation
PubMed: 28270558
DOI: 10.15252/msb.20167507 -
Clinical Interventions in Aging 2022The aim of the paper is to establish and quantify the relation between healthy ageing and the innate and adaptive immune parameters as indicators of age-related diseases.
PURPOSE
The aim of the paper is to establish and quantify the relation between healthy ageing and the innate and adaptive immune parameters as indicators of age-related diseases.
PATIENTS
In order to observe the immunological changes that occur according to age, several humoral and cellular immune parameters were investigated for 288 healthy donors (30-80 years). Subjects' selection was done using clinical, biochemical and immunological parameters of inclusion/exclusion criteria from SENIEUR protocol.
RESULTS
Age-related changes were observed for both humoral and cellular immune parameters. Lymphocyte immunophenotyping revealed several significant differences in the distribution of cells, both intra- and inter-age groups, namely decreased values of T-CD3, T-CD8 and NK cells, and elevated values for T-CD4, T-CD4/T-CD8 ratio and B cells. The percentages of unstimulated neutrophils that show basal oxidative activity and the intensity of this activity had an increasing tendency age-related. The percentage of N-Formyl-Methionyl-Leucyl-Phenylalanine stimulated neutrophils clearly decreases with age, and is associated with an increasing intensity of oxidative activity. Our data also have shown an increased percentage of oxidative neutrophils after phorbol 12-myristate 13-acetate stimulation and an elevated oxidative activity with age.
CONCLUSION
Overall healthy ageing is governed by some immune-related deregulations that account for immune exhaustion due to numerous developed immune processes during a life-time and the age-related diseases.
Topics: Acetates; Aged; Aged, 80 and over; Healthy Aging; Humans; Myristates; N-Formylmethionine Leucyl-Phenylalanine; Tetradecanoylphorbol Acetate
PubMed: 36247200
DOI: 10.2147/CIA.S375926 -
Psychoneuroendocrinology Feb 2021This study examined whether early life adversity (ELA) limited to infancy was associated with an increase in circulating levels of proinflammatory cytokines and cellular...
This study examined whether early life adversity (ELA) limited to infancy was associated with an increase in circulating levels of proinflammatory cytokines and cellular cytokine responses to three stimulants [lipopolysaccharide (LPS), phytohemagglutinin (PHA), and phorbol myristate acetate plus ionomycin (PMA/IO)]. Participants were previously institutionalized (PI) youth (N = 45, 56 % female) who had spent their first years in institutional care (e.g., orphanages, baby homes) before being adopted into well-resourced homes (median age at adoption = 13 mos) and non-adopted comparisons (NA; N = 38, 55 % female). Their age range was 13.3-21.2 years (M = 16.3 years). This analysis followed up an earlier report on these youth (Reid et al., 2019a) that identified an increase in terminally differentiated CD8 + CD57 T cells among the PI relative to the NA youth. Cytokine levels in circulation were not highly correlated and thus examined separately. PI youth had higher circulating levels of Tumor Necrosis Factor-alpha (TNFα), but not Interleukin-1β (IL-1β) or Interleukin-6 (IL-6). Cytokine responses to in vitro activation within each stimulant condition were highly correlated and were thus combined to generate an index of the inflammatory reaction to each stimulant. Using Multivariate Analysis of Covariance, there was a highly significant multivariate effect of group, which was carried primarily by the PMA/IO condition, with PI youth exhibiting a larger inflammatory response than NA youth. Tests of mediation showed that both the early rearing effects on circulating TNFα and the composite inflammatory index of PMA/IO responsiveness were mediated in the statistical model by the percentage of CD8 + CD57+ TEMRA cells in circulation, a marker of replicative senescence in T cells. Sex differences were also found in circulating levels of IL-6 and TNFα, with males having higher levels than females.
Topics: Adolescent; Adult; Cytokines; Female; Humans; Infant; Interleukin-6; Male; Orphanages; T-Lymphocytes; Tetradecanoylphorbol Acetate; Tumor Necrosis Factor-alpha; Young Adult
PubMed: 33278786
DOI: 10.1016/j.psyneuen.2020.105065 -
Journal of Agricultural and Food... Mar 2018Jatropha curcas is an important oilseed plant, with considerable potential in the development of biodiesel. Although Jatropha seed cake, the byproduct of oil extraction,... (Review)
Review
Jatropha curcas is an important oilseed plant, with considerable potential in the development of biodiesel. Although Jatropha seed cake, the byproduct of oil extraction, is a residue rich in nitrogen, phosphorus, potassium, and carbon, with high protein content suitable for application in animal feed, the presence of toxic phorbol esters limits its application in feed supplements and fertilizers. This review summarizes the current methods available for detoxification of this residue, based upon chemical, physical, biological, or combined processes. The advantages and disadvantages of each process are discussed, and future directions involving genomic and proteomic approaches for advancing our understanding of biodegradation processes involving microorganisms are highlighted.
Topics: Animal Feed; Biotechnology; Fertilizers; Jatropha; Phorbol Esters; Seeds; Waste Products
PubMed: 29498277
DOI: 10.1021/acs.jafc.7b05691 -
Journal of Ethnopharmacology Aug 2014Several species from the genus Sapium possess a broad range of medicinal properties and they have been used as traditional medicines by indigenous groups in several... (Review)
Review
ETHNOPHARMACOLOGICAL RELEVANCE
Several species from the genus Sapium possess a broad range of medicinal properties and they have been used as traditional medicines by indigenous groups in several regions such as Malaysia, Africa, Southern China and Bolivia. Most of the species reported to possess therapeutic effects which are used for the treatment of skin-related diseases such as eczema and dermatitis, but they may also be used for overstrain, lumbago, constipation and hernia. Species of this genus are also used to treat wounds and snake bites. In addition, the saps/latex of Sapium glandulosum, Sapium indicum and Sapium sebiferum have/has toxic effects and are used as bird and fish poisons. This review discusses the current knowledge of the medicinal uses, phytochemistry, biological activities and toxicities of species from the genus Sapium to reveal their therapeutic potentials and gaps offering opportunities for future research.
MATERIALS AND METHODS
This review is based on a literature study of scientific journals and books from libraries and electronic sources, such as ScienceDirect, PubMed and ACS.
RESULTS
As many as 65 compounds are included in this review. They belong to different classes of compounds including flavonoids, terpenoids and several other types of compounds, such as alkaloids, phenolic acids and amides. The pharmacological studies revealed that various types of preparations, extracts and single compounds of species from this genus exhibited a broad spectrum of biological activities including antioxidant, antimicrobial, anti-inflammatory and cytotoxic activities. However, Sapium glandulosum, Sapium indicum and Sapium sebiferum were reported to possess toxic effects and Sapium sebiferum was found to contain phorbol esters acting as a tumor-promoting agent.
CONCLUSION
The genus Sapium consists of 23 accepted (high confidence) species. However, only very few of species have been phytochemically and pharmacologically studied. There is great potential to discover new chemical constituents from this genus because only a few species have been phytochemically investigated thus far. Only 27 compounds of 65 identified compounds have been studied for their biological activities. Several extracts and single compounds from this genus were reported to exhibit interesting biological activities such as antimicrobial, antioxidant and cytotoxic effects. Furthermore, the toxicity studies of some phorbol esters suggested that the compounds acted as potential tumor-promoting agents by stimulating protein kinase C. This is an interesting fact in which a plant with medicinal properties also possesses toxic effects as well. Therefore, more clinical studies on the toxicity of the extracts of the plants and the compounds isolated from this genus are also crucial to ensure their safety and to assess their eligibility for use as sources for modern medicines.
Topics: Animals; Ethnopharmacology; Humans; Medicine, Traditional; Phytotherapy; Plant Extracts; Sapium
PubMed: 24877849
DOI: 10.1016/j.jep.2014.05.028 -
Journal of Cellular Biochemistry Dec 2017Stimulation of glucose transport is an important determinant of myocardial susceptibility to ischemia and reperfusion. Stimulation of glucose transport is markedly...
Stimulation of glucose transport is an important determinant of myocardial susceptibility to ischemia and reperfusion. Stimulation of glucose transport is markedly impaired in cardiomyocytes exposed to free fatty acids (FFA). Deactivation of the Focal Adhesion Kinase (FAK) by FFA contributes to glucose transport impairment, and could be corrected by chronic treatment with the phorbol ester TPA. However, TPA must have effects in addition to FAK reactivation to restore stimulated glucose transport. Chronic treatment with TPA improved basal and stimulated glucose transport in FFA-exposed, but not in control cardiomyocytes. Chronic FFA exposure induced the activation of PKCδ and PKCϵ. TPA markedly downregulated the expression of PKCα, PKCδ, and PKCϵ, suggesting that PKCδ or PKCϵ activation could contribute to inhibition of glucose transport by FFA. Rottlerin, a specific PKCδ inhibitor, improved glucose transport in FFA-exposed cardiomyocytes; and PKCδ was reduced in the particulate fraction of FFA + TPA-exposed cardiomyocytes. TPA also activated Protein Kinase D 1(PKD1) in FFA-exposed cardiomyocytes, as assessed by autophosphorylation of PKD1 on Y916. Pharmaceutical inhibition of PKD1 only partially prevented the improvement of glucose transport by TPA. Chronic TPA treatment also increased basal and stimulated glycolysis and favored accumulation of lipid droplets in FFA-exposed cardiomyocytes. In conclusion, basal and stimulated glucose transport in cardiomyocytes is reduced by chronic FFA exposure, but restored by concomitant treatment with a phorbol ester. The mechanism of action of phorbol esters may involve downregulation of PKCδ, activation of PKD1 and a general switch from fatty acid to glucose metabolism. J. Cell. Biochem. 9999: 4716-4727, 2017. © 2017 Wiley Periodicals, Inc.
Topics: Animals; Focal Adhesion Kinase 1; Glucose; Insulin Resistance; Male; Myocytes, Cardiac; Protein Kinase C; Rats; Rats, Sprague-Dawley; Tetradecanoylphorbol Acetate
PubMed: 28513986
DOI: 10.1002/jcb.26139