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Plants (Basel, Switzerland) Jun 2024An investigation of phenolic glycosides extracted from germplasm revealed that arbusculoidin (benzyl 1--β-d-glucopyranosyl-1-hydroxy-6-oxo-2-cyclohexenyl carboxylate)...
An investigation of phenolic glycosides extracted from germplasm revealed that arbusculoidin (benzyl 1--β-d-glucopyranosyl-1-hydroxy-6-oxo-2-cyclohexenyl carboxylate) and its enolic 6-glycoside isomer, isoarbusculoidin, are widespread across the Salix family. An analysis of natural hybrid species and progeny from a willow breeding programme demonstrated that the putative biosynthetic pathway leading to the salicinoid family of phenolic glycosides runs in parallel to a "benzyl"-based pathway to arbusculoidin. The introduction of a known Diels-Alder reaction trait from , as well as an acylation trait, into progeny containing both salicyl- and benzyl- pathways caused the formation of all possible hetero-cyclodimers from mixtures of reactive dienone (acyl)glycosides that participated in cross-over reactions. In addition to providing access to new analogues of the anti-cancer dimer miyabeacin, the analysis of the breeding progeny also indicated that these dienone (acyl)glycosides are stable in planta. Although the immediate biosynthetic precursors of these compounds remain to be defined, the results suggest that the (acyl)glycosylation reactions may occur later in the pathway than previously suggested by in vitro work on cloned UGT enzymes.
PubMed: 38931042
DOI: 10.3390/plants13121609 -
Molecules (Basel, Switzerland) Jun 2024A new series of chiral 4,5-dihydro-1-[1,2,4]-triazoline molecules, featuring a β-ᴅ-glucopyranoside appendage, were synthesized via a 1,3-dipolar cycloaddition...
Stereoselective Asymmetric Syntheses of Molecules with a 4,5-Dihydro-1-[1,2,4]-Triazoline Core Possessing an Acetylated Carbohydrate Appendage: Crystal Structure, Spectroscopy, and Pharmacology.
A new series of chiral 4,5-dihydro-1-[1,2,4]-triazoline molecules, featuring a β-ᴅ-glucopyranoside appendage, were synthesized via a 1,3-dipolar cycloaddition reaction between various hydrazonyl chlorides and carbohydrate Schiff bases. The isolated enantiopure triazolines (-) were identified through high-resolution mass spectrometry (HRMS) and vibrational spectroscopy. Subsequently, their solution structures were elucidated through NMR spectroscopic techniques. Single-crystal X-ray analysis of derivative provided definitive evidence for the 3-D structure of this compound and revealed important intermolecular forces in the crystal lattice. Moreover, it confirmed the ()-configuration at the newly generated stereo-center. Selected target compounds were investigated for anti-tumor activity in 60 cancer cell lines, with derivative showing the highest potency, particularly against leukemia. Additionally, substituent-dependent anti-fungal and anti-bacterial behavior was observed.
Topics: Humans; Crystallography, X-Ray; Triazoles; Cell Line, Tumor; Antineoplastic Agents; Carbohydrates; Molecular Structure; Stereoisomerism; Acetylation; Structure-Activity Relationship; Magnetic Resonance Spectroscopy
PubMed: 38930904
DOI: 10.3390/molecules29122839 -
Medicina (Kaunas, Lithuania) May 2024Chronic kidney disease (CKD) is characterized by persistent kidney dysfunction, ultimately resulting in end-stage renal disease (ESRD). Renal fibrosis is a crucial... (Review)
Review
Chronic kidney disease (CKD) is characterized by persistent kidney dysfunction, ultimately resulting in end-stage renal disease (ESRD). Renal fibrosis is a crucial pathological feature of CKD and ESRD. However, there is no effective treatment for this condition. Despite the complex molecular mechanisms involved in renal fibrosis, increasing evidence highlights the crucial role of histone modification in its regulation. The reversibility of histone modifications offers promising avenues for therapeutic strategies to block or reverse renal fibrosis. Therefore, a comprehensive understanding of the regulatory implications of histone modifications in fibrosis may provide novel insights into more effective and safer therapeutic approaches. This review highlights the regulatory mechanisms and recent advances in histone modifications in renal fibrosis, particularly histone methylation and histone acetylation. The aim is to explore the potential of histone modifications as targets for treating renal fibrosis.
Topics: Humans; Fibrosis; Histones; Renal Insufficiency, Chronic; Kidney; Acetylation; Methylation; Protein Processing, Post-Translational; Histone Code
PubMed: 38929505
DOI: 10.3390/medicina60060888 -
Foods (Basel, Switzerland) Jun 2024The wide ampelographic treasure of Italian wine grape varieties is driving research towards suitable approaches for the varietal authenticity control of wine. In this...
The wide ampelographic treasure of Italian wine grape varieties is driving research towards suitable approaches for the varietal authenticity control of wine. In this paper, Aglianico, Negroamaro, Primitivo and Uva di Troia red wines, which were produced experimentally by single-grape winemaking from non-aromatic grapes native to southern Italy, were analyzed with respect to berry markers, namely anthocyanins, hydroxycinnamic acids (HPLC-DAD), shikimic acid (HPLC-UV) and glycosidic aroma precursors (GC-MS). The study confirms that, just as for the berries, useful varietal authenticity markers for red wine, even after aging, turn out to be hydroxycinnamic acids, relative amounts of acylated forms of anthocyanins, and shikimic acid, together with some grape glycosidic precursors from terpenes and C- norisoprenoids. Principal Component Analysis was used as a valuable tool to highlight the results.
PubMed: 38928808
DOI: 10.3390/foods13121866 -
International Journal of Molecular... Jun 2024Extensive evidence supports the connection between obesity-induced inflammation and the heightened expression of IL-6 adipose tissues. However, the mechanism underlying...
Extensive evidence supports the connection between obesity-induced inflammation and the heightened expression of IL-6 adipose tissues. However, the mechanism underlying the IL-6 exacerbation in the adipose tissue remains unclear. There is general agreement that TNF-α and stearate concentrations are mildly elevated in adipose tissue in the state of obesity. We hypothesize that TNF-α and stearate co-treatment induce the increased expression of IL-6 in mouse adipocytes. We therefore aimed to determine IL-6 gene expression and protein production by TNF-α/stearate treated adipocytes and investigated the mechanism involved. To test our hypothesis, 3T3-L1 mouse preadipocytes were treated with TNF-α, stearate, or TNF-α/stearate. IL-6 gene expression was assessed by quantitative real-time qPCR. IL-6 protein production secreted in the cell culture media was determined by ELISA. Acetylation of histone was analyzed by Western blotting. Il6 region-associated histone H3 lysine 9/18 acetylation (H3K9/18Ac) was determined by ChIP-qPCR. 3T3-L1 mouse preadipocytes were co-challenged with TNF-α and stearate for 24 h, which led to significantly increased IL-6 gene expression (81 ± 2.1 Fold) compared to controls stimulated with either TNF-α (38 ± 0.5 Fold; = 0.002) or stearate (56 ± 2.0 Fold; = 0.013). As expected, co-treatment of adipocytes with TNF-α and stearate significantly increased protein production (338 ± 11 pg/mL) compared to controls stimulated with either TNF-α (28 ± 0.60 pg/mL; = 0.001) or stearate (53 ± 0.20 pg/mL, = 0.0015). Inhibition of histone acetyltransferases (HATs) with anacardic acid or curcumin significantly reduced the IL-6 gene expression and protein production by adipocytes. Conversely, TSA-induced acetylation substituted the stimulatory effect of TNF-α or stearate in their synergistic interaction for driving IL-6 gene expression and protein production. Mechanistically, TNF-α/stearate co-stimulation increased the promoter-associated histone H3 lysine 9/18 acetylation (H3K9/18Ac), rendering a transcriptionally permissive state that favored IL-6 expression at the transcriptional and translational levels. Our data represent a TNF-α/stearate cooperativity model driving IL-6 expression in 3T3-L1 cells via the H3K9/18Ac-dependent mechanism, with implications for adipose IL-6 exacerbations in obesity.
Topics: Animals; Mice; Histones; Interleukin-6; 3T3-L1 Cells; Tumor Necrosis Factor-alpha; Acetylation; Adipocytes; Stearic Acids; Gene Expression Regulation
PubMed: 38928498
DOI: 10.3390/ijms25126776 -
International Journal of Molecular... Jun 2024Histone acetyltransferases (HATs) modify the amino-terminal tails of the core histone proteins via acetylation, regulating chromatin structure and transcription. GENERAL...
Histone acetyltransferases (HATs) modify the amino-terminal tails of the core histone proteins via acetylation, regulating chromatin structure and transcription. GENERAL CONTROL NON-DEREPRESSIBLE 5 (GCN5) is a HAT that specifically acetylates H3K14 residues. GCN5 has been associated with cell division and differentiation, meristem function, root, stem, foliar, and floral development, and plant environmental response. The flowers of plants display a reduced stamen length and exhibit male sterility relative to the wild-type plants. We show that these effects may arise from gibberellin (GA)-signaling defects. The signaling pathway of bioactive GAs depends on the proteolysis of their repressors, DELLA proteins. The repressor GA (RGA) DELLA protein represses plant growth, inflorescence, and flower and seed development. Our molecular data indicate that GCN5 is required for the activation and H3K14 acetylation of genes involved in the late stages of GA biosynthesis and catabolism. We studied the genetic interaction of the RGA and GCN5; the RGA can partially suppress GCN5 action during the whole plant life cycle. The reduced elongation of the stamen filament of mutants is reversed in the double mutants. RGAs suppress the GCN5 effect on the gene expression and histone acetylation of GA catabolism and GA signaling. Interestingly, the RGA and RGL2 do not suppress ADA2b function, suggesting that ADA2b acts downstream of GA signaling and is distinct from GCN5 activity. In conclusion, we propose that the action of GCN5 on stamen elongation is partially mediated by RGA and GA signaling.
Topics: Arabidopsis; Gibberellins; Arabidopsis Proteins; Histone Acetyltransferases; Signal Transduction; Gene Expression Regulation, Plant; Acetylation; Flowers; Transcription Factors; Histones; Repressor Proteins
PubMed: 38928464
DOI: 10.3390/ijms25126757 -
International Journal of Molecular... Jun 2024The prevalence of dilated cardiomyopathy (DCM) is increasing globally, highlighting the need for innovative therapeutic approaches to prevent its onset. In this study,...
The prevalence of dilated cardiomyopathy (DCM) is increasing globally, highlighting the need for innovative therapeutic approaches to prevent its onset. In this study, we examined the energetic and epigenetic distinctions between dilated and non-dilated human myocardium-derived mesenchymal stem/stromal cells (hmMSCs) and assessed the effects of class I and II HDAC inhibitors (HDACi) on these cells and their cardiomyogenic differentiation. Cells were isolated from myocardium biopsies using explant outgrowth methods. Mitochondrial and histone deacetylase activities, ATP levels, cardiac transcription factors, and structural proteins were assessed using flow cytometry, PCR, chemiluminescence, Western blotting, and immunohistochemistry. The data suggest that the tested HDAC inhibitors improved acetylation and enhanced the energetic status of both types of cells, with significant effects observed in dilated myocardium-derived hmMSCs. Additionally, the HDAC inhibitors activated the cardiac transcription factors Nkx2-5, HOPX, GATA4, and Mef2C, and upregulated structural proteins such as cardiac troponin T and alpha cardiac actin at both the protein and gene levels. In conclusion, our findings suggest that HDACi may serve as potential modulators of the energetic status and cardiomyogenic differentiation of human heart hmMSCs. This avenue of exploration could broaden the search for novel therapeutic interventions for dilated cardiomyopathy, ultimately leading to improvements in heart function.
Topics: Humans; Histone Deacetylase Inhibitors; Mesenchymal Stem Cells; Cardiomyopathy, Dilated; Cell Differentiation; Myocardium; Histone Deacetylases; Myocytes, Cardiac; MEF2 Transcription Factors; Homeobox Protein Nkx-2.5; Acetylation; Transcription Factors; Cells, Cultured
PubMed: 38928463
DOI: 10.3390/ijms25126758 -
International Journal of Molecular... Jun 2024Epigenetic modulation, including histone modification, alters gene expression and controls cell fate. Histone deacetylases (HDACs) are identified as important regulators...
Epigenetic modulation, including histone modification, alters gene expression and controls cell fate. Histone deacetylases (HDACs) are identified as important regulators of dental pulp cell (DPC) mineralisation processes. Currently, there is a paucity of information regarding the nature of histone modification and HDAC expression in the dentine-pulp complex during dentinogenesis. The aim of this study was to investigate post-translational histone modulation and HDAC expression during DPC mineralisation and the expression of Class I/II HDACs during tooth development and in adult teeth. HDAC expression (isoforms -1 to -6) was analysed in mineralising primary rat DPCs using qRT-PCR and Western blot with mass spectrometry being used to analyse post-translational histone modifications. Maxillary molar teeth from postnatal and adult rats were analysed using immunohistochemical (IHC) staining for HDACs (1-6). HDAC-1, -2, and -4 protein expression increased until days 7 and 11, but decreased at days 14 and 21, while other HDAC expression increased continuously for 21 days. The Class II mineralisation-associated HDAC-4 was strongly expressed in postnatal sample odontoblasts and DPCs, but weakly in adult teeth, while other Class II HDACs (-5, -6) were relatively strongly expressed in postnatal DPCs and adult odontoblasts. Among Class I HDACs, HDAC-1 showed high expression in postnatal teeth, notably in ameloblasts and odontoblasts. HDAC-2 and -3 had extremely low expression in the rat dentine-pulp complex. Significant increases in acetylation were noted during DPC mineralisation processes, while trimethylation H3K9 and H3K27 marks decreased, and the HDAC-inhibitor suberoylanilide hydroxamic acid (SAHA) enhanced H3K27me3. These results highlight a dynamic alteration in histone acetylation during mineralisation and indicate the relevance of Class II HDAC expression in tooth development and regenerative processes.
Topics: Animals; Acetylation; Rats; Histone Deacetylases; Dentinogenesis; Dentin; Dental Pulp; Protein Processing, Post-Translational; Histones; Molar; Odontoblasts; Male
PubMed: 38928274
DOI: 10.3390/ijms25126569 -
Biomolecules Jun 2024Lysine acetylation of proteins plays a critical regulatory function in plants. A few advances have been made in the study of plant acetylproteome. However, until now,...
Lysine acetylation of proteins plays a critical regulatory function in plants. A few advances have been made in the study of plant acetylproteome. However, until now, there have been few data on Pall. (). We analyzed the molecular mechanisms of photosynthesis and stress resistance in under UV-B stress. We measured chlorophyll fluorescence parameters of under UV-B stress and performed a multi-omics analysis. Based on the determination of chlorophyll fluorescence parameters, Y(NO) (Quantum yield of non-photochemical quenching) increased under UV-B stress, indicating that the plant was damaged and photosynthesis decreased. In the analysis of acetylated proteomics data, acetylated proteins were found to be involved in a variety of biological processes. Notably, acetylated proteins were significantly enriched in the pathways of photosynthesis and carbon fixation, suggesting that lysine acetylation modifications have an important role in these activities. Our findings suggest that has decreased photosynthesis and impaired photosystems under UV-B stress, but NPQ shows that plants are resistant to UV-B. Acetylation proteomics revealed that up- or down-regulation of acetylation modification levels alters protein expression. Acetylation modification of key enzymes of the Calvin cycle (Rubisco, GAPDH) regulates protein expression, making Rubisco and GAPDH proteins expressed as significantly different proteins, which in turn affects the carbon fixation capacity of . Thus, Rubisco and GAPDH are significantly differentially expressed after acetylation modification, which affects the carbon fixation capacity and thus makes the plant resistant to UV-B stress. Lysine acetylation modification affects biological processes by regulating the expression of key enzymes in photosynthesis and carbon fixation, making plants resistant to UV-B stress.
Topics: Acetylation; Ultraviolet Rays; Photosynthesis; Carbon Cycle; Rhododendron; Ribulose-Bisphosphate Carboxylase; Stress, Physiological; Plant Proteins; Proteomics; Gene Expression Regulation, Plant; Chlorophyll; Lysine
PubMed: 38927135
DOI: 10.3390/biom14060732 -
Biomolecules Jun 2024Cytochrome (Cyt) is important for both mitochondrial respiration and apoptosis, both of which are altered in cancer cells that switch to Warburg metabolism and manage...
Cytochrome (Cyt) is important for both mitochondrial respiration and apoptosis, both of which are altered in cancer cells that switch to Warburg metabolism and manage to evade apoptosis. We earlier reported that lysine 53 (K53) of Cyt is acetylated in prostate cancer. K53 is conserved in mammals that is known to be essential for binding to cytochrome oxidase and apoptosis protease activating factor-1 (Apaf-1). Here we report the effects of this acetylation on the main functions of cytochrome by expressing acetylmimetic K53Q in cytochrome double knockout cells. Other cytochrome variants analyzed were wild-type, K53R as a control that maintains the positive charge, and K53I, which is present in some non-mammalian species. Intact cells expressing K53Q cytochrome showed 49% decreased mitochondrial respiration and a concomitant increase in glycolytic activity (Warburg effect). Furthermore, mitochondrial membrane potential was decreased, correlating with notably reduced basal mitochondrial superoxide levels and decreased cell death upon challenge with HO or staurosporine. To test for markers of cancer aggressiveness and invasiveness, cells were grown in 3D spheroid culture. K53Q cytochrome -expressing cells showed profoundly increased protrusions compared to WT, suggesting increased invasiveness. We propose that K53 acetylation of cytochrome is an adaptive response that mediates prostate cancer metabolic reprogramming and evasion of apoptosis, which are two hallmarks of cancer, to better promote tumor survival and metastasis.
Topics: Prostatic Neoplasms; Humans; Cytochromes c; Male; Acetylation; Apoptosis; Lysine; Cell Line, Tumor; Mitochondria; Membrane Potential, Mitochondrial; Metabolic Reprogramming
PubMed: 38927098
DOI: 10.3390/biom14060695