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Nutrients Jul 2021Dietary protamine can ameliorate hyperlipidemia; however, the protamine-derived active peptide and its hypolipidemic mechanism of action are unclear. Here, we report the...
Dietary protamine can ameliorate hyperlipidemia; however, the protamine-derived active peptide and its hypolipidemic mechanism of action are unclear. Here, we report the discovery of a novel anti-obesity and hypocholesterolemic peptide, RPR (Arg-Pro-Arg), derived from protamine in mice fed a high-fat diet for 50 days. Serum cholesterol levels were significantly lower in the protamine and RPR groups than in the control group. White adipose tissue weight was significantly decreased in the protamine and RPR groups. The fecal excretion of cholesterol and bile acid was significantly higher in the protamine and RPR groups than in the control group. We also observed a significant decrease in the expression of hepatic SCD1, SREBP1, and adipocyte FAS mRNA, and significantly increased expression of hepatic PPARα and adipocyte PPARγ1 mRNA in the protamine group. These findings demonstrate that the anti-obesity effects of protamine are linked to the upregulation of adipocyte PPARγ1 and hepatic PPARα and the downregulation of hepatic SCD1 via SREBP1 and adipocyte FAS. RPR derived from protamine has a crucial role in the anti-obesity action of protamine by evaluating the effective dose of adipose tissue weight loss.
Topics: Adipose Tissue, White; Adiposity; Animals; Anti-Obesity Agents; Anticholesteremic Agents; Biomarkers; Cholesterol; Diet, High-Fat; Disease Models, Animal; Fatty Acid Synthase, Type I; Liver; Male; Mice, Inbred C57BL; Obesity; Oligopeptides; PPAR alpha; PPAR gamma; Protamines; Stearoyl-CoA Desaturase; Sterol Regulatory Element Binding Protein 1; Weight Loss; Mice
PubMed: 34444660
DOI: 10.3390/nu13082501 -
European Journal of Case Reports in... 2020Heparin is commonly used in clinical practice for the prevention and treatment of various thrombotic conditions. Its use can be associated with bleeding which can range...
UNLABELLED
Heparin is commonly used in clinical practice for the prevention and treatment of various thrombotic conditions. Its use can be associated with bleeding which can range from minor to life threatening. Non-traumatic causes of breast haematoma are very rare. We report a case of spontaneous bleeding into the breast in a female patient who was anticoagulated with heparin.
LEARNING POINTS
Anticoagulant use can be associated with the adverse effect of bleeding at various sites.Physicians should be cautious of such bleeding which can occur at unsuspected sites.Our patient developed spontaneous breast haematoma after unfractionated heparin anticoagulation, and was successfully managed with cessation of anticoagulation, protamine, desmopressin and blood transfusion.
PubMed: 32908833
DOI: 10.12890/2020_001735 -
Frontiers in Genetics 2020The genome of eukaryotes is highly organized within the cell nucleus, this organization elicits gene regulation and favors other mechanisms like cell memory throughout... (Review)
Review
The genome of eukaryotes is highly organized within the cell nucleus, this organization elicits gene regulation and favors other mechanisms like cell memory throughout histones and their post-translational modifications. In highly specialized cells, like sperm, the genome is mostly organized by protamines, yet a significant portion of it remains organized by histones. This protamine-histone-DNA organization, known as sperm epigenome, is established during spermiogenesis. Specific histones and their post-translational modifications are retained at specific genomic sites and during embryo development these sites recapitulate their histone profile that harbored in the sperm nucleus. It is known that histones are the conduit of epigenetic memory from cell to cell, hence histones in the sperm epigenome may have a role in transmitting epigenetic memory from the sperm to the embryo. However, the exact function and mechanism of histone retention remains elusive. During spermatogenesis, most of the histones that organize the genome are replaced by protamines and their retention at specific regions may be deeply intertwined with the eviction and replacement mechanism. In this review we will cover some relevant aspects of histone replacement that in turn may help us to contextualize histone retention. In the end, we focus on the architectonical protein CTCF that is, so far, the only factor that has been directly linked to the histone retention process.
PubMed: 32765595
DOI: 10.3389/fgene.2020.00780 -
BMC Cardiovascular Disorders May 2022Compared to simple percutaneous coronary intervention (PCI), complex PCI is associated with higher bleeding and thrombotic risk. No previous study has evaluated the use...
BACKGROUND
Compared to simple percutaneous coronary intervention (PCI), complex PCI is associated with higher bleeding and thrombotic risk. No previous study has evaluated the use of protamine after PCI with contemporary technologies. This study aimed to evaluate the safety and efficacy of manual compression with and without protamine after transfemoral complex PCI.
METHODS
We retrospectively analyzed 160 patients (protamine group, n = 92; non-protamine group, n = 68) who underwent complex PCI via the femoral artery. The primary outcome was a composite of in-hospital death, myocardial infarction, stent thrombosis, stroke/systemic embolism, bleeding requiring blood transfusion, and vascular access complications.
RESULTS
The primary outcome was significantly lower in the protamine group than in the non-protamine group (4.3% vs. 17.6%; p = 0.006). This was driven mainly by the lower incidences of hematoma in the protamine group (3.3% vs. 13.2%, p = 0.020). Furthermore, the protamine group had a significantly shorter hospital stay than the non-protamine group (4.8 ± 3.7 days vs. 8.4 ± 8.3 days, p = 0.001). While > 90% of the patients had acute coronary syndrome, there were no incidences of myocardial infarction or stent thrombosis in either group.
CONCLUSIONS
Among patients who underwent complex PCI via transfemoral access, immediate protamine administration was associated with a significantly lower rate of vascular access complications, especially hematoma, and shorter hospital stay than no protamine administration.
Topics: Anticoagulants; Hematoma; Hemorrhage; Heparin; Hospital Mortality; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Protamines; Retrospective Studies; Thrombosis; Treatment Outcome
PubMed: 35538419
DOI: 10.1186/s12872-022-02650-5 -
Frontiers in Psychiatry 2023To investigate the correlations between thyroid function, renal function, and depression.
OBJECTIVE
To investigate the correlations between thyroid function, renal function, and depression.
METHODS
Clinical data of 67 patients with Major depressive disorder (MDD) and 36 healthy control subjects between 2018 and 2021 were collected to compare thyroid and renal function. Thyroid and renal functions of depressed patients were then correlated with the Hamilton Depression Rating Scale (HAMD) and the Hamilton Anxiety Rating Scale (HAMA).Spearman correlation analysis was used to find the correlation between renal function, thyroid function, and depression. A logistic regression was performed to find significant predictors of depression.
RESULTS
Triiodothyronine protamine (T3), thyroxine (T4), free triiodothyronine protamine (FT3), uric acid, sodium, and anion gap were lower in the MDD group than in the control group ( < 0.05). Correlation analysis of thyroid function, renal function, and factor terms of HAMD in the MDD group suggested that diurnal variation, hopelessness, and depression level were positively correlated with thyrotropin (TSH) ( < 0.05). Cognitive disturbance, retardation, and depression level were negatively correlated with creatinine ( < 0.05). Diurnal variation was negatively correlated with sodium ion ( < 0.01); hopelessness and depression level were positively correlated with chloride ion ( < 0.05); diurnal variation, retardation, and depression level were negatively correlated with anion gap ( < 0.05). Diurnal variation ( < 0.01) and retardation ( < 0.05) were negatively correlated with osmolality. Cognitive disturbance and depression level were positively correlated with estimated glomerular filtration rate (eGFR) ( < 0.05). In the MDD group, correlation analysis of thyroid function, renal function, and HAMA factor terms suggested that the total HAMA score and anxiety level were positively correlated with chloride ion ( < 0.05); psychic anxiety, total HAMA score, and anxiety level were negatively correlated with anion gap ( < 0.05). Furthermore, a low level of anion gap was an independent risk factor for depression and anxiety levels ( < 0.05).
CONCLUSION
Low thyroid function and reduced waste metabolized by the kidneys in patients with MDD suggest a low intake and low metabolism in depressed patients. In addition, subtle fluctuations in the anion gap in depressed patients were strongly correlated with the degree of depression and anxiety.
PubMed: 38179254
DOI: 10.3389/fpsyt.2023.1182657 -
Frontiers in Genetics 2019Spermiogenesis is a complex cellular differentiation process that the germ cells undergo a distinct morphological change, and the protamines replace the core histones to... (Review)
Review
Spermiogenesis is a complex cellular differentiation process that the germ cells undergo a distinct morphological change, and the protamines replace the core histones to facilitate chromatin compaction in the sperm head. Recent studies show the essential roles of epigenetic events during the histone-to-protamine transition. Defects in either the replacement or the modification of histones might cause male infertility with azoospermia, oligospermia or teratozoospermia. Here, we summarize recent advances in our knowledge of how epigenetic regulators, such as histone variants, histone modification and their related chromatin remodelers, facilitate the histone-to-protamine transition during spermiogenesis. Understanding the molecular mechanism underlying the modification and replacement of histones during spermiogenesis will enable the identification of epigenetic biomarkers of male infertility, and shed light on potential therapies for these patients in the future.
PubMed: 31649732
DOI: 10.3389/fgene.2019.00962 -
Annals of Cardiac Anaesthesia 2021Protamine is routinely administered to neutralize the anticlotting effects of heparin, traditionally at a dose of 1 mg for every 100 IU of heparin-a 1:1 ratio protamine... (Observational Study)
Observational Study
CONTEXT
Protamine is routinely administered to neutralize the anticlotting effects of heparin, traditionally at a dose of 1 mg for every 100 IU of heparin-a 1:1 ratio protamine sparing effects-but this is based more on experience and practice than literature evidence. The use of Hemostasis Management System (HMS) allows an individualized heparin and protamine titration. This usually results in a decreased protamine dose, thus limiting its side effects, including paradox anticoagulation.
AIMS
This study aims to assess how the use of HMS allows to reduction of protamine administration while restoring the basal activated clotting time (ACT) at the end of cardiac surgery.
SETTINGS AND DESIGN
A retrospective observational study in a tertiary care university hospital.
SUBJECTS AND METHODS
We analyzed data from 42 consecutive patients undergoing cardiopulmonary bypass (CPB) for cardiac surgery. For all patients HMS tests were performed before and after CPB, to determine how much heparin was needed to reach target ACT, and how much protamine was needed to reverse it.
RESULTS
At the end of cardiopulmonary bypass, 2.2 ± 0.5 mg/kg of protamine was sufficient to reverse heparin effects. The protamine-to-heparin ratio was 0.56:1 over heparin total dose (a 44% reduction) and 0.84:1 over heparin initial dose (a 16% reduction).
CONCLUSION
A lower dose of protamine was sufficient to revert heparin effects after cardiopulmonary bypass. While larger studies are needed to confirm these findings and detect differences in clinically relevant outcomes, the administration of a lower protamine dose is endorsed by current guidelines and may help to avoid the detrimental effects of protamine overdose, including paradox bleeding.
Topics: Anticoagulants; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Heparin; Heparin Antagonists; Humans; Protamines; Whole Blood Coagulation Time
PubMed: 33884973
DOI: 10.4103/aca.ACA_26_19 -
American Journal of Clinical and... 2021Sperm selection without - or with a low level of - protamine deficiency and DNA fragmentation is a remarkable indicator to increase the success rate of ICSI outcomes....
OBJECTIVE
Sperm selection without - or with a low level of - protamine deficiency and DNA fragmentation is a remarkable indicator to increase the success rate of ICSI outcomes. The aim of this study was to compare sperm selection methods in the elimination of sperm with protamine deficiency and DNA fragmentation and their effects on ICSI Outcomes in oligoteratzoospermia patients.
METHODS
Semen samples were obtained from oligoteratozoospermia patients undergoing ICSI. Sperm selection was conducted using Zona Pellucida (ZP) binding, Hyaluronic Acid (HA) binding, and conventional PVP methods. SCD assay and CMA3 staining were used for the detection of sperm protamine deficiency and DNA fragmentation. Good quality of the embryo, blastocyst formation, chemical, and clinical pregnancy rates among studied groups was evaluated and compared.
RESULTS
Our results indicated the percentage of sperm DNA fragmentation and protamine deficiency were lower significantly in the HA- and ZP-bound sperm. Although no significant differences were observed in the fertilization rate among studied methods, good quality of cleavage embryo rates were increased using ZP and HA methods versus the conventional PVP method. However, there were no significant differences in cleavage and embryo quality between the HA compared to the ZP method. Blastocyst formation, chemical and clinical pregnancy rates increased in the HA method.
CONCLUSIONS
Overall, the HA method for sperm selection due to high sensitivity in selecting sperm with a low level of DNA fragmentation and protamine deficiency is a very useful method to increase the success rate of ICSI outcomes in oligoteratozoospermia patients.
PubMed: 34079849
DOI: No ID Found -
Nature Nov 2022Sperm chromatin is typically transformed by protamines into a compact and transcriptionally inactive state. Sperm cells of flowering plants lack protamines, yet they...
Sperm chromatin is typically transformed by protamines into a compact and transcriptionally inactive state. Sperm cells of flowering plants lack protamines, yet they have small, transcriptionally active nuclei with chromatin condensed through an unknown mechanism. Here we show that a histone variant, H2B.8, mediates sperm chromatin and nuclear condensation in Arabidopsis thaliana. Loss of H2B.8 causes enlarged sperm nuclei with dispersed chromatin, whereas ectopic expression in somatic cells produces smaller nuclei with aggregated chromatin. This result demonstrates that H2B.8 is sufficient for chromatin condensation. H2B.8 aggregates transcriptionally inactive AT-rich chromatin into phase-separated condensates, which facilitates nuclear compaction without reducing transcription. Reciprocal crosses show that mutation of h2b.8 reduces male transmission, which suggests that H2B.8-mediated sperm compaction is important for fertility. Altogether, our results reveal a new mechanism of nuclear compaction through global aggregation of unexpressed chromatin. We propose that H2B.8 is an evolutionary innovation of flowering plants that achieves nuclear condensation compatible with active transcription.
Topics: Arabidopsis; Chromatin; Histones; Protamines; Pollen; Gene Expression Regulation, Plant; AT Rich Sequence; Cell Nucleus; Mutation; Cell Nucleus Size; Phase Transition; Cell Size; Transcription, Genetic
PubMed: 36323776
DOI: 10.1038/s41586-022-05386-6 -
Nucleic Acids Research Jul 2022Spermatogenesis is precisely controlled by sophisticated gene expression programs and is driven by epigenetic reprogramming, including histone modification alterations...
Spermatogenesis is precisely controlled by sophisticated gene expression programs and is driven by epigenetic reprogramming, including histone modification alterations and histone-to-protamine transition. Nuclear receptor binding SET domain protein 2 (Nsd2) is the predominant histone methyltransferase catalyzing H3K36me2 and its role in male germ cell development remains elusive. Here, we report that NSD2 protein is abundant in spermatogenic cells. Conditional loss of Nsd2 in postnatal germ cells impaired fertility owing to apoptosis of spermatocytes and aberrant spermiogenesis. Nsd2 deficiency results in dysregulation of thousands of genes and remarkable reduction of both H3K36me2 and H3K36me3 in spermatogenic cells, with H3K36me2 occupancy correlating positively with expression of germline genes. Nsd2 deficiency leads to H4K16ac elevation in spermatogenic cells, probably through interaction between NSD2 and PSMA8, which regulates acetylated histone degradation. We further reveal that Nsd2 deficiency impairs EP300-induced H4K5/8ac, recognized by BRDT to mediate the eviction of histones. Accordingly, histones are largely retained in Nsd2-deficient spermatozoa. In addition, Nsd2 deficiency enhances expression of protamine genes, leading to increased protamine proteins in Nsd2-deficient spermatozoa. Our findings thus reveal a previously unappreciated role of the Nsd2-dependent chromatin remodeling during spermatogenesis and provide clues to the molecular mechanisms in epigenetic abnormalities impacting male reproductive health.
Topics: Humans; Male; Epigenomics; Histone-Lysine N-Methyltransferase
PubMed: 35736136
DOI: 10.1093/nar/gkac533