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Antioxidants (Basel, Switzerland) May 2024Antioxidants protect cellular function and structure by neutralizing the oxidative stress caused by increased reactive oxygen species (ROS) during sperm freezing....
Antioxidants protect cellular function and structure by neutralizing the oxidative stress caused by increased reactive oxygen species (ROS) during sperm freezing. Studies on cryopreservation using various antioxidants have demonstrated encouraging results. Many studies have used antioxidants to increase the efficiency of sperm freezing and to improve the success rate of artificial insemination and pregnancy. Manganese (III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) is a newly synthesized antioxidant with positive effects on sperm morphology and capacitation in humans, rams, and stallions. In this study, porcine semen was treated with 0, 50, 100, and 150 μM of MnTBAP based on a Tris-egg-yolk extender and frozen to determine whether MnTBAP can assist the status of sperm during cryopreservation. First, motility was assessed using the computer-assisted sperm analysis (CASA) system, with the 100 μM treatment group showing the highest motile rate (66.8%) compared with that of the other groups (control, 51.1%; 50 μM and 150 μM, 59.6%); therefore, the remaining analyses were conducted comparing the two groups (control vs. 100 μM group; < 0.01). Second, fluorescence staining was applied to examine the control and 100 μM groups using fluorescence microscopy. The viability (41.7% vs. 62.4%) and the acrosome integrity (77.9% vs. 86.4%) differed significantly ( < 0.05). In addition, the mitochondrial membrane potential (MMP) was 46.5% vs. 51.9%; the fragmentation rate, estimated using the Sperm-sus-Halomax kit, was 63.4% vs. 57.4%; and the detected caspase activity was 30.1% vs. 22.9%. These tended to be higher in the treated group but did not differ significantly. Third, measurements using FACSLyric revealed that the 100 μM treatment group exhibited a state of elevated normal lipid arrangement within the plasma membrane and diminished levels of apoptosis and ROS ( < 0.01). We assessed the expression of genes relevant to antioxidant effectiveness using real-time RT-qPCR. Our findings indicated significant alterations in the expression levels of various mRNA species, with the exception of NOX5 ( < 0.05). Finally, the straws were dissolved and used to treat matured denuded oocytes to investigate the effect on fertilization and embryo development in vitro. The cleavage rate was (77.6% vs. 84.1%), and the blastocyst rate was 9.7% vs. 11.4% ( < 0.05). In conclusion, these results suggest that MnTBAP positively affected sperm freeze-thawing, improving the fertilization capacity, and leading to increased embryo development.
PubMed: 38929111
DOI: 10.3390/antiox13060672 -
International Journal of Molecular... Jun 2024Hell's Gate globin-I (HGb-I) is a thermally stable globin from the aerobic methanotroph . Here we report that HGb-I interacts with lipids stoichiometrically to induce...
Hell's Gate globin-I (HGb-I) is a thermally stable globin from the aerobic methanotroph . Here we report that HGb-I interacts with lipids stoichiometrically to induce structural changes in the heme pocket, changing the heme iron distal ligation coordination from hexacoordinate to pentacoordinate. Such changes in heme geometry have only been previously reported for cytochrome c and cytoglobin, linked to apoptosis regulation and enhanced lipid peroxidation activity, respectively. However, unlike cytoglobin and cytochrome c, the heme iron of HGb-I is altered by lipids in ferrous as well as ferric oxidation states. The apparent affinity for lipids in this thermally stable globin is highly pH-dependent but essentially temperature-independent within the range of 20-60 °C. We propose a mechanism to explain these observations, in which lipid binding and stability of the distal endogenous ligand are juxtaposed as a function of temperature. Additionally, we propose that these coupled equilibria may constitute a mechanism through which this acidophilic thermophile senses the pH of its environment.
Topics: Hydrogen-Ion Concentration; Temperature; Globins; Lipids; Heme; Protein Conformation; Models, Molecular; Bacterial Proteins
PubMed: 38928500
DOI: 10.3390/ijms25126794 -
International Journal of Molecular... Jun 2024Ferrochelatase (FECH) is the terminal enzyme in human heme biosynthesis, catalyzing the insertion of ferrous iron into protoporphyrin IX (PPIX) to form protoheme IX...
Ferrochelatase (FECH) is the terminal enzyme in human heme biosynthesis, catalyzing the insertion of ferrous iron into protoporphyrin IX (PPIX) to form protoheme IX (Heme). Phosphorylation increases the activity of FECH, and it has been confirmed that the activity of FECH phosphorylated at T116 increases. However, it remains unclear whether the T116 site and other potential phosphorylation modification sites collaboratively regulate the activity of FECH. In this study, we identified a new phosphorylation site, T218, and explored the allosteric effects of unphosphorylated (UP), PT116, PT218, and PT116 + PT218 states on FECH in the presence and absence of substrates (PPIX and Heme) using molecular dynamics (MD) simulations. Binding free energies were evaluated with the MM/PBSA method. Our findings indicate that the PT116 + PT218 state exhibits the lowest binding free energy with PPIX, suggesting the strongest binding affinity. Additionally, this state showed a higher binding free energy with Heme compared to UP, which facilitates Heme release. Moreover, employing multiple analysis methods, including free energy landscape (FEL), principal component analysis (PCA), dynamic cross-correlation matrix (DCCM), and hydrogen bond interaction analysis, we demonstrated that phosphorylation significantly affects the dynamic behavior and binding patterns of substrates to FECH. Insights from this study provide valuable theoretical guidance for treating conditions related to disrupted heme metabolism, such as various porphyrias and iron-related disorders.
Topics: Ferrochelatase; Humans; Phosphorylation; Molecular Dynamics Simulation; Heme; Protoporphyrins; Catalytic Domain; Protein Binding; Binding Sites; Thermodynamics
PubMed: 38928065
DOI: 10.3390/ijms25126360 -
Genes Jun 2024We conducted transcriptome sequencing on salt-tolerant mutants X5 and X3, and a control (Ctr) strain of after treatment with artificial seawater at varying salinities...
We conducted transcriptome sequencing on salt-tolerant mutants X5 and X3, and a control (Ctr) strain of after treatment with artificial seawater at varying salinities (30‱, 45‱, and 60‱) for 3 weeks. Differentially expressed genes were identified and a weighted co-expression network analysis was conducted. The blue, red, and tan modules were most closely associated with salinity, while the black, cyan, light cyan, and yellow modules showed a close correlation with strain attributes. KEGG enrichment of genes from the aforementioned modules revealed that the key enrichment pathways for salinity attributes included the proteasome and carbon fixation in photosynthesis, whereas the key pathways for strain attributes consisted of lipid metabolism, oxidative phosphorylation, soluble N-ethylmaleimide-sensitive factor-activating protein receptor (SNARE) interactions in vesicular transport, and porphyrin and chlorophyll metabolism. Gene expression for the proteasome and carbon fixation in photosynthesis was higher in all strains at 60‱. In addition, gene expression in the proteasome pathway was higher in the X5-60 than Ctr-60 and X3-60. Based on the above data and relevant literature, we speculated that mutant X5 likely copes with high salt stress by upregulating genes related to lysosome and carbon fixation in photosynthesis. The proteasome may be reset to adjust the organism's proteome composition to adapt to high-salt environments, while carbon fixation may aid in maintaining material and energy metabolism for normal life activities by enhancing carbon dioxide uptake via photosynthesis. The differences between the X5-30 and Ctr-30 expression of genes involved in the synthesis of secondary metabolites, oxidative phosphorylation, and SNARE interactions in vesicular transport suggested that the X5-30 may differ from Ctr-30 in lipid metabolism, energy metabolism, and vesicular transport. Finally, among the key pathways with good correlation with salinity and strain traits, the key genes with significant correlation with salinity and strain traits were identified by correlation analysis.
Topics: Salt Tolerance; Transcriptome; Gene Regulatory Networks; Salinity; Photosynthesis; Osmotic Pressure; Proteasome Endopeptidase Complex; Gene Expression Profiling; Lipid Metabolism
PubMed: 38927717
DOI: 10.3390/genes15060781 -
Genes May 2024LONP1 is the principal AAA+ unfoldase and bulk protease in the mitochondrial matrix, so its deletion causes embryonic lethality. The AAA+ unfoldase CLPX and the... (Review)
Review
Knockout Mouse Studies Show That Mitochondrial CLPP Peptidase and CLPX Unfoldase Act in Matrix Condensates near IMM, as Fast Stress Response in Protein Assemblies for Transcript Processing, Translation, and Heme Production.
LONP1 is the principal AAA+ unfoldase and bulk protease in the mitochondrial matrix, so its deletion causes embryonic lethality. The AAA+ unfoldase CLPX and the peptidase CLPP also act in the matrix, especially during stress periods, but their substrates are poorly defined. Mammalian CLPP deletion triggers infertility, deafness, growth retardation, and cGAS-STING-activated cytosolic innate immunity. CLPX mutations impair heme biosynthesis and heavy metal homeostasis. CLPP and CLPX are conserved from bacteria to humans, despite their secondary role in proteolysis. Based on recent proteomic-metabolomic evidence from knockout mice and patient cells, we propose that CLPP acts on phase-separated ribonucleoprotein granules and CLPX on multi-enzyme condensates as first-aid systems near the inner mitochondrial membrane. Trimming within assemblies, CLPP rescues stalled processes in mitoribosomes, mitochondrial RNA granules and nucleoids, and the D-foci-mediated degradation of toxic double-stranded mtRNA/mtDNA. Unfolding multi-enzyme condensates, CLPX maximizes PLP-dependent delta-transamination and rescues malformed nascent peptides. Overall, their actions occur in granules with multivalent or hydrophobic interactions, separated from the aqueous phase. Thus, the role of CLPXP in the matrix is compartment-selective, as other mitochondrial peptidases: MPPs at precursor import pores, m-AAA and i-AAA at either IMM face, PARL within the IMM, and OMA1/HTRA2 in the intermembrane space.
Topics: Endopeptidase Clp; Animals; Mice; Mitochondria; Mitochondrial Proteins; Mice, Knockout; Heme; Protein Biosynthesis; Humans; Mitochondrial Membranes; Stress, Physiological
PubMed: 38927630
DOI: 10.3390/genes15060694 -
Journal of Nanobiotechnology Jun 2024As an emerging cancer treatment strategy, reactive oxygen species-based tumor catalytic therapies face enormous challenges due to hypoxia and the overexpression of...
As an emerging cancer treatment strategy, reactive oxygen species-based tumor catalytic therapies face enormous challenges due to hypoxia and the overexpression of glutathione (GSH) in the tumor microenvironment. Herein, a self-assembled copper-based nanoplatform, TCCHA, was designed for enzyme-like catalysis-enhanced chemodynamic/photodynamic/antiangiogenic tritherapy against hepatocellular carcinoma. TCCHA was fabricated from Cu, 3,3'-dithiobis (propionohydrazide), and photosensitizer chlorine e6 via a facile one-pot self-assembly strategy, after which an aldehyde hyaluronic acid was coated, followed by loading of the antivascular drug AL3818. The obtained TCCHA nanoparticles exhibited pH/GSH dual-responsive drug release behaviors and multienzymatic activities, including Fenton, glutathione peroxidase-, and catalase-like activities. TCCHA, a redox homeostasis disruptor, promotes ⋅OH generation and GSH depletion, thus increasing the efficacy of chemodynamic therapy. TCCHA, which has catalase-like activity, can also reinforce the efficacy of photodynamic therapy by amplifying O production. In vivo, TCCHA efficiently inhibited tumor angiogenesis and suppressed tumor growth without apparent systemic toxicity. Overall, this study presents a facile strategy for the preparation of multienzyme-like nanoparticles, and TCCHA nanoparticles display great potential for enzyme catalysis-enhanced chemodynamic/photodynamic/antiangiogenic triple therapy against cancer.
Topics: Copper; Animals; Carcinoma, Hepatocellular; Photochemotherapy; Liver Neoplasms; Mice; Humans; Photosensitizing Agents; Mice, Inbred BALB C; Cell Line, Tumor; Reactive Oxygen Species; Angiogenesis Inhibitors; Porphyrins; Chlorophyllides; Glutathione; Nanoparticles; Catalysis; Metal Nanoparticles; Drug Liberation; Mice, Nude; Antineoplastic Agents
PubMed: 38926721
DOI: 10.1186/s12951-024-02626-x -
Advanced Materials (Deerfield Beach,... Jun 2024Polyoxometalates (POMs) have been considered as one of the most promising anode candidates for lithium-ion batteries (LIBs) in virtue of their high theoretical capacity...
Polyoxometalates (POMs) have been considered as one of the most promising anode candidates for lithium-ion batteries (LIBs) in virtue of their high theoretical capacity and reversible multielectron redox properties. However, the poor intrinsic electronic conductivity, low specific surface area and high solubility in organic electrolytes hinder their widespread applications in LIBs. Herein, a novel hybrid nanomaterial is synthesized by co-assembling POMs and porphyrins (PMo/CoTPyP) through a facile solvothermal method. The POMs clusters are stabilized by porphyrin units through electrostatic interactions, which simultaneously realizes the uniform dispersion of POMs and porphyrin units. Benefiting from the generated sub-1 nm channels for fast ion transport and the synergistic effect between evenly distributed PMo clusters and high-conductive CoTPyP units, the LIB based on the optimized PMo/CoTPyP anode exhibits significant improved Li storage capability as well as superior rate and cycling performance. The results of density functional theory (DFT) simulations further reveal that the co-assembly of PMo and CoTPyP can accelerate the mobility of Li and electrons, which in turn promotes the enhancement of LIBs performance. This work paves a strategy for synthesizing POMs-based anode materials with simultaneously high dispersibility, redox activity and stability. This article is protected by copyright. All rights reserved.
PubMed: 38925587
DOI: 10.1002/adma.202407705 -
Chemistry (Weinheim An Der Bergstrasse,... Jun 2024Corrole is a tetrapyrrolic dye with a structure that resembles porphyrin, apart from a single missing carbon. The absence of this carbon results in the re-arrangement of...
Corrole is a tetrapyrrolic dye with a structure that resembles porphyrin, apart from a single missing carbon. The absence of this carbon results in the re-arrangement of the double bonds within the macrocycle, and the presence of three pyrrolic protons in the central cavity in its free base form. These protons lead to the existence of two distinct tautomeric structures that exist in a dynamic equilibrium. Although the ground state energies of the tautomers are similar, the excited states show a significant difference in energy which unbalances the equilibrium between the tautomers and results in rapid excited state tautomerization, favouring one tautomeric species over the other. Although the excited state tautomerization process has been known for a long time, very few studies have been performed on it leaving many key aspects of the process poorly understood. Herein we show how ultrafast photoluminescence can be used to experimentally determine the rates of excited state tautomerization and activation energies of three free base corrole derivatives thus allowing us to completely describe the excited state dynamics of the unusual, excited state of free base corrole and opening the door to the development of new materials that can exploit it unique characteristics..
PubMed: 38925567
DOI: 10.1002/chem.202401709 -
Journal of Hazardous Materials Jun 2024Based on multiple ligands strategy, a series of multivariate metal organic frameworks (MTV-MOFs) named as PCN-224-DCDPS were prepared using one-pot solvothermal method...
Based on multiple ligands strategy, a series of multivariate metal organic frameworks (MTV-MOFs) named as PCN-224-DCDPS were prepared using one-pot solvothermal method to extract and remove sulfonamide antibiotics (SAs). The pore structure and adsorption performance can be further regulated by modulating the doping ratios of medium-tetra(4-carboxylphenyl) porphyrin and 4,4'-dicarboxydiphenyl sulfones. The MTV-MOFs of PCN-224-DCDPS possesses very large specific surface area (1625 m/g). Using PCN-224-DCDPS as sorbent, a dispersive solid-phase extraction method was developed to extract and preconcentrate SAs from water, eggs, and milk prior to high performance liquid chromatography analysis. The limits of detection of method were determined between 0.17 and 0.27 ng/mL with enrichment factors ranging 214-327. The adsorption can be finished within 30 s, and the recovery rate remains above 80 % after 10 repeated uses. The adsorption capacities of sorbent were determined from 300 to 621 mg/g for sulfadiazine, sulphapyridine, sulfamethoxydiazine, sulfachlorpyridazine, sulfabenzamide, and sulfadimethoxine. The adsorption mechanisms were investigated and can be attributed to π-π interactions, hydrogen bonds, and electrostatic interactions. This work represents a method for preparation of MTV-MOFs and uses as sorbent for extraction and enrichment of trace pollutants from complex samples.
PubMed: 38925054
DOI: 10.1016/j.jhazmat.2024.135019 -
ChemMedChem Jun 2024Studies have shown that folate receptors are highly expressed in various cancer cells. Here, we synthesized folic acid-conjugated pullulan (FAPL) as a solubilizing agent...
Studies have shown that folate receptors are highly expressed in various cancer cells. Here, we synthesized folic acid-conjugated pullulan (FAPL) as a solubilizing agent to improve the photodynamic activity of porphyrin derivative-polysaccharide complexes. The porphyrin derivative-FAPL complex exhibited long-term stability in an aqueous solution, attributed to the folic acid modification. Furthermore, in vitro and in vivo experiments highlighted the enhanced photodynamic activity of the porphyrin derivative-FAPL complex toward 4T1 breast-cancer cells, compared with the activities of the porphyrin derivative-pullulan complex and Photofrin. This enhanced activity is attributed to the improvement of intracellular uptake by the folate receptor.
PubMed: 38924356
DOI: 10.1002/cmdc.202400268