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Cell Death & Disease May 2024Precise polyamine metabolism regulation is vital for cells and organisms. Mutations in spermine synthase (SMS) cause Snyder-Robinson intellectual disability syndrome...
Precise polyamine metabolism regulation is vital for cells and organisms. Mutations in spermine synthase (SMS) cause Snyder-Robinson intellectual disability syndrome (SRS), characterized by significant spermidine accumulation and autophagy blockage in the nervous system. Emerging evidence connects polyamine metabolism with other autophagy-related diseases, such as Tauopathy, however, the functional intersection between polyamine metabolism and autophagy in the context of these diseases remains unclear. Here, we altered SMS expression level to investigate the regulation of autophagy by modulated polyamine metabolism in Tauopathy in Drosophila and human cellular models. Interestingly, while complete loss of Drosophila spermine synthase (dSms) impairs lysosomal function and blocks autophagic flux recapitulating SRS disease phenotype, partial loss of dSms enhanced autophagic flux, reduced Tau protein accumulation, and led to extended lifespan and improved climbing performance in Tauopathy flies. Measurement of polyamine levels detected a mild elevation of spermidine in flies with partial loss of dSms. Similarly, in human neuronal or glial cells, partial loss of SMS by siRNA-mediated knockdown upregulated autophagic flux and reduced Tau protein accumulation. Importantly, proteomics analysis of postmortem brain tissue from Alzheimer's disease (AD) patients showed a significant albeit modest elevation of SMS level. Taken together, our study uncovers a functional correlation between polyamine metabolism and autophagy in AD: SMS reduction upregulates autophagy, suppresses Tau accumulation, and ameliorates neurodegeneration and cell death. These findings provide a new potential therapeutic target for AD.
Topics: Autophagy; Animals; tau Proteins; Humans; Spermine Synthase; Drosophila melanogaster; Drosophila Proteins; Tauopathies; Neurons; Alzheimer Disease; Spermidine; Disease Models, Animal; Lysosomes; Drosophila; Mental Retardation, X-Linked
PubMed: 38740758
DOI: 10.1038/s41419-024-06720-8 -
Journal of the Science of Food and... May 2024The excessive salt intake associated with Douchi has become a topic of controversy. Addressing this concern and enhancing its market competitiveness necessitates the...
BACKGROUND
The excessive salt intake associated with Douchi has become a topic of controversy. Addressing this concern and enhancing its market competitiveness necessitates the application of salt reduction fermentation in Douchi. Therefore, to promote the application of salt reduction fermentation in Douchi, a comprehensive study was undertaken aiming to investigate the differences in biogenic amines, volatile compounds and non-volatile compounds in Douchi with varying salt content.
RESULTS
The findings unequivocally demonstrate that salt hampers the formation of metabolites in Douchi. As the salt content increased, there was a significant decrease (P < 0.05) in the levels of total acid, amino-type nitrogen and free amino acids in Douchi. Notably, when the salt content exceeded 80 g kg, there was a substantial reduction (P < 0.05) in putrescine, lactic acid and malic acid levels. Similarly, when the salt content surpassed 40 g kg, β-phenethylamine and oxalic acid levels exhibited a significant decline (P < 0.05). Furthermore, the results of E-nose and principal component analysis based on headspace solid phase microextraction gas chromatography-mass spectrometry revealed notable discrepancies in the volatile compound content between Douchi samples with relatively low salt content (40 and 80 g kg) and those with relatively high salt content (120, 160 and 200 g kg) (P < 0.05). By employing partial least squares discriminant analysis, eight distinct volatile compounds, including o-xylene, benzaldehyde and 1-octen-one, were identified. These compounds exhibited higher concentrations in Douchi samples with relatively low salt content (40 and 80 g kg). The sensory results showed that Douchi samples with lower salt content exhibited higher scores in the soy sauce-like and Douchi aroma attributes.
CONCLUSION
In conclusion, this study significantly enhances our understanding of the impact of salt on metabolites in Douchi and provides invaluable insights for the development of salt reduction fermentation in this context. © 2024 Society of Chemical Industry.
PubMed: 38738583
DOI: 10.1002/jsfa.13574 -
Plants (Basel, Switzerland) Apr 2024Five putrescine and spermidine derivatives (-) together with five rotenoids (-) were isolated from a methanolic extract of the flowers of that displayed promising...
Five putrescine and spermidine derivatives (-) together with five rotenoids (-) were isolated from a methanolic extract of the flowers of that displayed promising inhibition of 76.0 ± 1.9% for AChE and 90.0 ± 4.0% for BuChE at a concentration of 1 mg/mL. Although the anticholinesterase activities of the isolated compounds did not reach that of galantamine, molecular docking revealed that all--tri--coumaroylspermidine and ---tri--coumaroylspermidine showed binding poses mimicking the known inhibitor galantamine and thus could serve as model molecules in future searches for new AChE and BuChE inhibitors.
PubMed: 38732396
DOI: 10.3390/plants13091181 -
Journal of Affective Disorders Aug 2024Spermidine (SPD) has a number of advantageous effects, including life extension and neuroprotection. However, few observational studies have investigated the association...
BACKGROUND
Spermidine (SPD) has a number of advantageous effects, including life extension and neuroprotection. However, few observational studies have investigated the association of dietary SPD intake with depression.
METHODS
We used data from the 2005-2014 National Health and Nutrition Examination Survey (NHANES) and the corresponding Food Patterns Equivalents Database (FPED). SPD content of food groups from published data were merged with the appropriate FPED data to estimate the SPD intake for each subject. Patients with Patient Health Questionnaire-9 (PHQ-9) scores of 10 or above were thought to experience clinically relevant depression symptoms. Logistic regression, sensitivity analysis, and restricted cubic spline (RCS) were used.
RESULTS
Among the 19,306 participants, the overall prevalence of depression was 8.72 %. After controlling for relevant confounders, individuals in the highest tertile or quartile of total SPD and SPD derived from fruits, vegetables, cereals, nuts, eggs and seafood had a significantly lower prevalence of depression (OR total SPD = 0.77, 95 % CI: 0.63-0.93); OR fruit-sourced SPD = 0.81, 95 % CI: 0.68-0.95; OR vegetable-sourced SPD = 0.72, 95 % CI: 0.61-0.85; OR cereals-sourced SPD = 0.73,95 % CI:0.60-0.88; OR nuts- sourced SPD = 0.80, 95 % CI: 0.71-0.91; OR egg-sourced = 0.72, 95 % CI: 0.62-0.84 and OR seafood-sourced SPD = 0.65, 95 % CI: 0.55-0.77) comparing those in the lowest tertile or quartile.
CONCLOUSION
Our fndings reveal a negative association between dietary SPD intake and depression.
Topics: Humans; Male; Female; Nutrition Surveys; Adult; United States; Depression; Middle Aged; Spermidine; Diet; Prevalence; Young Adult; Cross-Sectional Studies; Aged
PubMed: 38729223
DOI: 10.1016/j.jad.2024.05.041 -
Food Chemistry Sep 2024Rye leaven, the basic constituent of sour rye soup ('żurek' or white borsch), was obtained through three methods of initiating lacto-fermentation of rye flour. Optimal...
Rye leaven, the basic constituent of sour rye soup ('żurek' or white borsch), was obtained through three methods of initiating lacto-fermentation of rye flour. Optimal concentrations of NaCl (1.5%) and garlic (0.5%) were selected by utilizing the response surface methodology. During the production and storage of leaven at 10 °C and 20 °C, the secalin proteins of rye flour degraded significantly and the concentration of free amino acids increased, making the rye leaven an environment potentially conducive to the formation of biogenic amines. Putrescine (max. conc: 116.7 mg kg) and tyramine (max. conc: 63.4 mg kg) were the amines that occurred in the largest amounts in the leavens. The final concentration of histamine (after 150 days of storage) did not exceed 22 mg kg. Regardless of the method of initiation of fermentation, the products that contained fewer biogenic amines better retained their sensory characteristics (r ≤ -0.89, p < 0.05) and had a higher number of lactic acid bacteria (r ≤ -0.66, p < 0.05).
Topics: Biogenic Amines; Secale; Food Storage; Fermentation; Flour; Humans; Taste
PubMed: 38728889
DOI: 10.1016/j.foodchem.2024.139523 -
RSC Chemical Biology May 2024The enzymatic synthesis of xenobiotic nucleic acids (XNA), which are artificially sugar-modified nucleic acids, is essential for the preparation of XNA libraries. XNA...
The enzymatic synthesis of xenobiotic nucleic acids (XNA), which are artificially sugar-modified nucleic acids, is essential for the preparation of XNA libraries. XNA libraries are used in the selection of XNA aptamers and enzymes (XNAzymes). Efficient enzymatic synthesis of various XNAs can enable the screening of high-quality XNA aptamers and XNAzymes by expanding the diversity of XNA libraries and adding a variety of properties to XNA aptamers and XNAzymes. However, XNAs that form unstable duplexes with DNA, such as arabino nucleic acid (ANA), may dissociate during enzyme synthesis at temperatures suitable for thermophilic polymerases. Thus, such XNAs are not efficiently synthesised by the thermophilic polymerase mutants at the end of the sequence. This undesirable bias reduces the possibility of generating high-quality XNA aptamers and XNAzymes. Here, we demonstrate that polyamine-induced DNA/ANA duplex stabilisation promotes ANA synthesis that is catalysed by thermophilic polymerase mutants. Several polyamines, including spermine, spermidine, cadaverine, and putrescine promote ANA synthesis. The negative effect of polyamines on the fidelity of ANA synthesis was negligible. We also showed that polyamines promote the synthesis of other XNAs, including 2'-amino-RNA/2'-fluoro-RNA mixture and 2'--methyl-RNA. In addition, we found that polyamine promotes DNA synthesis from the 2'--methyl-RNA template. Polyamines, with the use of thermophilic polymerase mutants, may allow further development of XNA aptamers and XNAzymes by promoting the transcription and reverse transcription of XNAs.
PubMed: 38725908
DOI: 10.1039/d4cb00017j -
Nuclear Medicine and Biology 2024The polyamine transporter system (PTS), which renders it a promising target for tumor therapy and imaging applications, facilitates the transmembrane transport of...
BACKGROUND
The polyamine transporter system (PTS), which renders it a promising target for tumor therapy and imaging applications, facilitates the transmembrane transport of polyamines. We reported a novel derivative of spermine labeled with gallium-68 ([Ga]Ga-NOTA-Spermine) for the imaging of the PTS in mouse models of tumor.
RESULTS
The radiochemical yield of [Ga]Ga-NOTA-Spermine was determined to be 64-69 %, demonstrating exceptional stability and radiochemical purity (>98 %). Cellular uptake experiments revealed that A549 cells exhibited peak uptake of [Ga]Ga-NOTA-Spermine at 90 min (15.4 % ± 0.68 %). Biodistribution analysis demonstrated significant accumulation of [Ga]Ga-NOTA-Spermine in kidneys and liver, while exhibiting low uptake levels in muscle, brain, and bones. Furthermore, Micro-PET/CT scans conducted on A549 tumor-bearing mouse models indicated substantial uptake of [Ga]Ga-NOTA-Spermine, with maximum tumor/muscle (T/M) ratios reaching 3.71.
CONCLUSION
These results suggest that [Ga]Ga-NOTA-Spermine holds potential as a PET imaging agent for tumors with high levels of PTS.
Topics: Animals; Gallium Radioisotopes; Mice; Spermine; Humans; Tissue Distribution; Isotope Labeling; Chemistry Techniques, Synthetic; Positron-Emission Tomography; Positron Emission Tomography Computed Tomography; A549 Cells; Radiochemistry; Biological Transport; Heterocyclic Compounds, 1-Ring
PubMed: 38723361
DOI: 10.1016/j.nucmedbio.2024.108915 -
Spectrochimica Acta. Part A, Molecular... Sep 2024Over the years, osteosarcoma therapy has had a significative improvement with the use of a multidrug regime strategy, increasing the survival rates from less than 20 %...
Over the years, osteosarcoma therapy has had a significative improvement with the use of a multidrug regime strategy, increasing the survival rates from less than 20 % to circa 70 %. Different types of development of new antineoplastic agents are critical to achieve irreversible damage to cancer cells, while preserving the integrity of their healthy counterparts. In the present study, complexes with two and three Pd(II) centres linked by the biogenic polyamines: spermine (PdSpmCl) and spermidine (PdSpdCl) were tested against non-malignant (osteoblasts, HOb) and cancer (osteosarcoma, MG-63) human cell lines. Either alone or in combination according to the EURAMOS-1 protocol, they were used versus cisplatin as a drug reference. By evaluating the cytotoxic effects of both therapeutic approaches (single and drug combination) in HOb and MG-63 cell lines, the selective anti-tumoral potential is assessed. To understand the different treatments at a molecular level, Synchrotron Radiation Fourier Transform Infrared and Raman microspectroscopies were applied. Principal component analysis and hierarchical cluster analysis are applied to the vibrational data, revealing the major metabolic changes caused by each drug, which were found to rely on DNA, lipids, and proteins, acting as biomarkers of drug-to-cell impact. The main changes were observed for the B-DNA native conformation to either Z-DNA (higher in the presence of polynuclear complexes) or A-DNA (preferably after cisplatin exposure). Additionally, a higher effect upon variation in proteins content was detected in drug combination when compared to single drug administration proving the efficacy of the EURAMOS-1 protocol with the new drugs tested.
Topics: Humans; Osteosarcoma; Spectrum Analysis, Raman; Antineoplastic Agents; Cell Line, Tumor; Spectroscopy, Fourier Transform Infrared; Vibration; Spermine; Bone Neoplasms; Spermidine; Principal Component Analysis; Cell Survival
PubMed: 38710137
DOI: 10.1016/j.saa.2024.124389 -
ACS Omega Apr 2024This study aimed to verify the presence of biogenic amines (BAs) and evaluate the microbiological activity of some food samples collected from retail stores in the...
This study aimed to verify the presence of biogenic amines (BAs) and evaluate the microbiological activity of some food samples collected from retail stores in the Kingdom of Saudi Arabia. A total of thirty-five dairy and fish products were collected and analyzed for BAs, including putrescine (PUT), cadaverine (CAD), spermidine (SPE), histamine (HIS), spermine (SPR), and tyramine (TYR), as well as for total colony count (TCC), lactic acid bacteria (LAB), Enterobacteriaceae, yeast and mold (Y and M), coliforms, and aerobic sporulation count (ASF). The thin layer chromatography (TLC) method was used in the analytical methodology to identify the BAs. The results showed the presence of BAs in all dairy products, but their concentration did not exceed the maximum permissible limit, which in contrast was established by the Food and Drug Administration (FDA) at 10 mg/100 g. The amounts of BAs in fish products varied significantly. All fish product samples contained levels of BAs below the permissible limit. Results of an independent study also indicated potential toxicity at levels of BAs (>10 mg/100 g) in Egyptian herring. Enterobacteriaceae and the coli group were present in higher concentrations in the Egyptian herring samples, whereas other samples (particularly frozen shrimp) showed increased TCC levels with a higher concentration of histamine-producing bacteria. From a consumer safety perspective, this study also indicated that food samples generally contained acceptable levels of BAs. In conclusion, there is a need to improve and standardize food quality and hygiene practices during production and storage to ensure human safety and prevent HIS formation.
PubMed: 38708229
DOI: 10.1021/acsomega.3c10347 -
Synthetic and Systems Biotechnology Sep 2024Spermidine is a naturally occurring polyamine widely utilized in the prevention and treatment of various diseases. Current spermidine biosynthetic methods have problems...
Spermidine is a naturally occurring polyamine widely utilized in the prevention and treatment of various diseases. Current spermidine biosynthetic methods have problems such as low efficiency and complex multi-enzyme catalysis. Based on sequence-structure-function relationships, we engineered the widely studied homospermidine synthase from (HSS) and obtained mutants that could catalyze the production of spermidine from 1,3-diaminopropane and putrescine. The specific activities of HSS and the mutants D361E and E232D + D361E (E232D-D) were 8.72, 46.04 and 48.30 U/mg, respectively. The optimal pH for both mutants was 9.0, and the optimal temperature was 50 °C. Molecular docking and dynamics simulations revealed that mutating aspartic acid at position 361 to glutamic acid narrowed the substrate binding pocket, promoting stable spermidine production. Conversely, mutating glutamic acid at position 232 to aspartic acid enlarged the substrate channel entrance, facilitating substrate entry into the active pocket and enhancing spermidine generation. In whole-cell catalysis lasting 6 h, D361E and E232D-D synthesized 725.3 and 933.5 mg/L of spermidine, respectively. This study offers a practical approach for single-enzyme catalyzed spermidine synthesis and sheds light on the crucial residues influencing homospermidine synthase catalytic activity in spermidine production.
PubMed: 38699566
DOI: 10.1016/j.synbio.2024.04.012