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Animal Science Journal = Nihon Chikusan... 2024In Japan, the promotion of effective use of many wild deer as food resource has been conducted. However, they are not necessarily utilized effectively. Thus, we focused... (Comparative Study)
Comparative Study
In Japan, the promotion of effective use of many wild deer as food resource has been conducted. However, they are not necessarily utilized effectively. Thus, we focused physiologically functional compounds to find characteristics of Sika deer meats (commercially available) obtained from different regions such as Hokkaido, Wakayama, Tokushima, and Miyazaki prefectures in Japan, making it a valuable resource for future studies and applications. The amount of carnosine, anserine, and balenine in muscle of deer from Wakayama prefecture was significantly lower than that in muscle of deer from other prefectures. The differences of amount of imidazole dipeptides in different prefectures seems to be caused by feed, rearing environment, and breed. The amount of carnitine in deer meat from Hokkaido was significantly lower than that in muscle of deer from other prefectures, while the amount of acetyl-carnitine in deer meat from Miyazaki prefectures was significantly higher than that from other prefectures. The amounts of glutamine, ornithine, and 3-methylhistidine in muscles of deer from Wakayama prefectures were significantly higher than those in muscle of deer from other prefectures. These results might be caused by differences in feeding habits, habitat, the muscle types, and subspecies of deer obtained from four regions in Japan.
Topics: Animals; Deer; Japan; Meat; Carnosine; Carnitine; Ornithine; Glutamine; Histidine; Anserine; Feeding Behavior; Muscle, Skeletal; Food Analysis
PubMed: 38924234
DOI: 10.1111/asj.13967 -
Biotechnology and Applied Biochemistry Jun 2024In spite of 150 years of studying malaria, the unique features of the malarial parasite, Plasmodium, still perplex researchers. One of the methods by which the parasite...
In spite of 150 years of studying malaria, the unique features of the malarial parasite, Plasmodium, still perplex researchers. One of the methods by which the parasite manages its gene expression is epigenetic regulation, the champion of which is PfGCN5, an essential enzyme responsible for acetylating histone proteins. PfGCN5 is a ∼170 kDa chromatin-remodeling enzyme that harbors the conserved bromodomain and acetyltransferase domain situated in its C-terminus domain. Although the PfGCN5 proteolytic processing is essential for its activity, the specific protease involved in this process still remains elusive. Identification of PfGCN5 interacting proteins through immunoprecipitation (IP) followed by LC-tandem mass spectrometry analysis revealed the presence of food vacuolar proteins, such as the cysteine protease Falcipain 3 (FP3), in addition to the typical members of the PfGCN5 complex. The direct interaction between FP3 and PfGCN5 was further validated by in vitro pull-down assay as well as IP assay. Subsequently, use of cysteine protease inhibitor E64d led to the inhibition of protease-specific processing of PfGCN5 with concomitant enrichment and co-localization of PfGCN5 and FP3 around the food vacuole as evidenced by confocal microscopy as well as electron microscopy. Remarkably, the proteolytic cleavage of the nuclear protein PfGCN5 by food vacuolar protease FP3 is exceptional and atypical in eukaryotic organisms. Targeting the proteolytic processing of GCN5 and the associated protease FP3 could provide a novel approach for drug development aimed at addressing the growing resistance of parasites to current antimalarial drugs.
PubMed: 38924147
DOI: 10.1002/bab.2630 -
Acta Obstetricia Et Gynecologica... Jun 2024Physical activity (PA) during pregnancy has numerous benefits, which may be mediated via effects on the immune system. However, supportive evidence is inconsistent and...
INTRODUCTION
Physical activity (PA) during pregnancy has numerous benefits, which may be mediated via effects on the immune system. However, supportive evidence is inconsistent and is mainly from studies in high-risk groups. We estimated the effect of PA during pregnancy on systemic inflammatory markers and cytokines in mothers recruited in the Barwon infant study.
MATERIAL AND METHODS
The Barwon infant study is a prebirth cohort of 1064 mothers recruited in the Barwon Region of Victoria, Australia. Participants reported their previous week's PA at their 28-week antenatal appointment using the International PA Questionnaire. Women were grouped into low, moderate, and high PA categories based on daily duration and weekly frequency of walking, moderate- or vigorous-intensity PA. Women reporting moderate levels of PA, consistent with current recommendations, served as the comparison group. Markers of systemic inflammation, high-sensitivity C-reactive protein (hsCRP), glycoprotein acetyls (GlycA), and 17 cytokines were measured at 28 weeks gestation and log transformed as appropriate. Regression analyses adjusted for maternal smoking, gestational diabetes mellitus, prepregnancy BMI, and household size were performed.
RESULTS
Compared to women in the moderate group (n = 371, 42%), women reporting low PA (n = 436, 50%) had 10.1% higher hsCRP (95% CI (3.7% to 16.6%), p < 0.01) while women in high PA (n = 76, 9%) had a 14% higher hsCRP (95% CI (3.1% to 24.8%), p = 0.01). Women in the high PA category had higher interleukin (IL)-4 (q = 0.03) and IL-9 (q = 0.03) levels compared to those in moderate category. Each vigorous MET minute/week was associated with lower GlycA (β = -0.004, 95% CI (-0.044 to 0.035); p = 0.03).
CONCLUSIONS
Low and high PA are each associated with higher hsCRP than moderate PA, suggesting that undertaking the recommended moderate PA during pregnancy decreases systemic inflammation. High PA affects T cell-associated cytokines during pregnancy. Evidence from our study suggests that PA can modulate the immune responses during pregnancy. Studies are now required to assess whether PA during pregnancy impacts maternal and infant clinical outcomes by modifying inflammatory responses.
PubMed: 38924074
DOI: 10.1111/aogs.14870 -
Proteomics. Clinical Applications Jun 2024Diabetic kidney disease (DKD) is a serious complication of diabetes mellitus and a leading cause of chronic kidney disease and end-stage renal disease. One potential...
PURPOSE
Diabetic kidney disease (DKD) is a serious complication of diabetes mellitus and a leading cause of chronic kidney disease and end-stage renal disease. One potential mechanism underlying cellular dysfunction contributing to kidney disease is aberrant protein post-translational modifications. Lysine acetylation is associated with cellular metabolic flux and is thought to be altered in patients with diabetes and dysfunctional renal metabolism.
EXPERIMENTAL DESIGN
A novel extraction and LC-MS/MS approach was adapted to quantify sites of lysine acetylation from formalin-fixed paraffin-embedded (FFPE) kidney tissue and from patients with DKD and non-diabetic donors (n = 5 and n = 7, respectively).
RESULTS
Analysis of FFPE tissues identified 840 total proteins, with 225 of those significantly changing in patients with DKD. Acetylomic analysis quantified 289 acetylated peptides, with 69 of those significantly changing. Pathways impacted in DKD patients revealed numerous metabolic pathways, specifically mitochondrial function, oxidative phosphorylation, and sirtuin signaling. Differential protein acetylation in DKD patients impacted sirtuin signaling, valine, leucine, and isoleucine degradation, lactate metabolism, oxidative phosphorylation, and ketogenesis.
CONCLUSIONS AND CLINICAL RELEVANCE
A quantitative acetylomics platform was developed for protein biomarker discovery in formalin-fixed and paraffin-embedded biopsies of kidney transplant patients suffering from DKD.
PubMed: 38923810
DOI: 10.1002/prca.202400018 -
The FEBS Journal Jun 2024Especially in higher eukaryotes, the N termini of proteins are subject to enzymatic modifications, with the acetylation of the alpha-amino group of nascent polypeptides... (Review)
Review
Especially in higher eukaryotes, the N termini of proteins are subject to enzymatic modifications, with the acetylation of the alpha-amino group of nascent polypeptides being a prominent one. In recent years, the specificities and substrates of the enzymes responsible for this modification, the Nα-terminal acetyltransferases, have been mapped in several proteomic studies. Aberrant expression of, and mutations in these enzymes were found to be associated with several human diseases, explaining the growing interest in protein Nα-terminal acetylation. With some enzymes, such as the Nα-terminal acetyltransferase A complex having thousands of possible substrates, researchers are now trying to decipher the functional outcome of Nα-terminal protein acetylation. In this review, we zoom in on one possible functional consequence of Nα-terminal protein acetylation; its effect on protein folding. Using selected examples of proteins associated with human diseases such as alpha-synuclein and huntingtin, here, we discuss the sometimes contradictory findings of the effects of Nα-terminal protein acetylation on protein (mis)folding and aggregation.
PubMed: 38923676
DOI: 10.1111/febs.17209 -
Open Biology Jun 2024is the predominant mould pathogen for humans. Adaption to host-imposed iron limitation has previously been demonstrated to be essential for its virulence. [2Fe-2S]...
is the predominant mould pathogen for humans. Adaption to host-imposed iron limitation has previously been demonstrated to be essential for its virulence. [2Fe-2S] clusters are crucial as cofactors of several metabolic pathways and mediate cytosolic/nuclear iron sensing in fungi including . [2Fe-2S] cluster trafficking has been shown to involve BolA family proteins in both mitochondria and the cytosol/nucleus. Interestingly, both homologues, termed Bol1 and Bol3, possess mitochondrial targeting sequences, suggesting the lack of cytosolic/nuclear versions. Here, we show by the combination of mutational, proteomic and fluorescence microscopic analyses that expression of the Bol3 encoding gene leads to dual localization of gene products to mitochondria and the cytosol/nucleus via alternative translation initiation downstream of the mitochondrial targeting sequence, which appears to be highly conserved in various species. Lack of either mitochondrial Bol1 or Bol3 was phenotypically inconspicuous while lack of cytosolic/nuclear Bol3 impaired growth during iron limitation but not iron sensing which indicates a particular importance of [2Fe-2S] cluster trafficking during iron limitation. Remarkably, cytosolic/nuclear Bol3 differs from the mitochondrial version only by N-terminal acetylation, a finding that was only possible by mutational hypothesis testing.
Topics: Aspergillus fumigatus; Fungal Proteins; Cytosol; Mitochondria; Iron; Adaptation, Physiological; Cell Nucleus; Protein Transport; Proteomics; Iron-Sulfur Proteins; Gene Expression Regulation, Fungal; Acetylation
PubMed: 38919062
DOI: 10.1098/rsob.240033 -
Biomedical Engineering Online Jun 2024Diabetic retinopathy (DR) is an eye disease that causes blindness and vision loss in diabetic. Risk factors for DR include high blood glucose levels and some... (Review)
Review
Diabetic retinopathy (DR) is an eye disease that causes blindness and vision loss in diabetic. Risk factors for DR include high blood glucose levels and some environmental factors. The pathogenesis is based on inflammation caused by interferon and other nuclear proteins. This review article provides an overview of DR and discusses the role of nuclear proteins in the pathogenesis of the disease. Some core proteins such as MAPK, transcription co-factors, transcription co-activators, and others are part of this review. In addition, some current advanced treatment resulting from the role of nuclear proteins will be analyzes, including epigenetic modifications, the use of methylation, acetylation, and histone modifications. Stem cell technology and the use of nanobiotechnology are proposed as promising approaches for a more effective treatment of DR.
Topics: Diabetic Retinopathy; Humans; Nuclear Proteins; Animals; Epigenesis, Genetic
PubMed: 38918766
DOI: 10.1186/s12938-024-01258-4 -
Scientific Reports Jun 2024Due to its involvement in physiological and pathological processes, histone deacetylase 6 (HDAC6) is considered a promising pharmaceutical target for several...
Due to its involvement in physiological and pathological processes, histone deacetylase 6 (HDAC6) is considered a promising pharmaceutical target for several neurological manifestations. However, the exact regulatory role of HDAC6 in the central nervous system (CNS) is still not fully understood. Hence, using a semi-automated literature screening technique, we systematically collected HDAC6-protein interactions that are experimentally validated and reported in the CNS. The resulting HDAC6 network encompassed 115 HDAC6-protein interactions divided over five subnetworks: (de)acetylation, phosphorylation, protein complexes, regulatory, and aggresome-autophagy subnetworks. In addition, 132 indirect interactions identified through HDAC6 inhibition were collected and categorized. Finally, to display the application of our HDAC6 network, we mapped transcriptomics data of Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis on the network and highlighted that in the case of Alzheimer's disease, alterations predominantly affect the HDAC6 phosphorylation subnetwork, whereas differential expression within the deacetylation subnetwork is observed across all three neurological disorders. In conclusion, the HDAC6 network created in the present study is a novel and valuable resource for the understanding of the HDAC6 regulatory mechanisms, thereby providing a framework for the integration and interpretation of omics data from neurological disorders and pharmacodynamic assessments.
Topics: Histone Deacetylase 6; Humans; Protein Interaction Maps; Nervous System Diseases; Alzheimer Disease; Phosphorylation; Acetylation; Parkinson Disease
PubMed: 38918466
DOI: 10.1038/s41598-024-65094-1 -
Nature Communications Jun 2024Heparan sulfate (HS) is degraded in lysosome by a series of glycosidases. Before the glycosidases can act, the terminal glucosamine of HS must be acetylated by the...
Heparan sulfate (HS) is degraded in lysosome by a series of glycosidases. Before the glycosidases can act, the terminal glucosamine of HS must be acetylated by the integral lysosomal membrane enzyme heparan-α-glucosaminide N-acetyltransferase (HGSNAT). Mutations of HGSNAT cause HS accumulation and consequently mucopolysaccharidosis IIIC, a devastating lysosomal storage disease characterized by progressive neurological deterioration and early death where no treatment is available. HGSNAT catalyzes a unique transmembrane acetylation reaction where the acetyl group of cytosolic acetyl-CoA is transported across the lysosomal membrane and attached to HS in one reaction. However, the reaction mechanism remains elusive. Here we report six cryo-EM structures of HGSNAT along the reaction pathway. These structures reveal a dimer arrangement and a unique structural fold, which enables the elucidation of the reaction mechanism. We find that a central pore within each monomer traverses the membrane and controls access of cytosolic acetyl-CoA to the active site at its luminal mouth where glucosamine binds. A histidine-aspartic acid catalytic dyad catalyzes the transfer reaction via a ternary complex mechanism. Furthermore, the structures allow the mapping of disease-causing variants and reveal their potential impact on the function, thus creating a framework to guide structure-based drug discovery efforts.
Topics: Mucopolysaccharidosis III; Humans; Lysosomes; Acetyltransferases; Cryoelectron Microscopy; Catalytic Domain; Mutation; Heparitin Sulfate; Acetyl Coenzyme A; Models, Molecular; Glucosamine; Acetylation; Intracellular Membranes
PubMed: 38918376
DOI: 10.1038/s41467-024-49614-1 -
Nature Communications Jun 2024Oxygen homeostasis is maintained in plants and animals by O-sensing enzymes initiating adaptive responses to low O (hypoxia). Recently, the O-sensitive enzyme ADO was...
Oxygen homeostasis is maintained in plants and animals by O-sensing enzymes initiating adaptive responses to low O (hypoxia). Recently, the O-sensitive enzyme ADO was shown to initiate degradation of target proteins RGS4/5 and IL32 via the Cysteine/Arginine N-degron pathway. ADO functions by catalysing oxidation of N-terminal cysteine residues, but despite multiple proteins in the human proteome having an N-terminal cysteine, other endogenous ADO substrates have not yet been identified. This could be because alternative modifications of N-terminal cysteine residues, including acetylation, prevent ADO-catalysed oxidation. Here we investigate the relationship between ADO-catalysed oxidation and NatA-catalysed acetylation of a broad range of protein sequences with N-terminal cysteines. We present evidence that human NatA catalyses N-terminal cysteine acetylation in vitro and in vivo. We then show that sequences downstream of the N-terminal cysteine dictate whether this residue is oxidised or acetylated, with ADO preferring basic and aromatic amino acids and NatA preferring acidic or polar residues. In vitro, the two modifications appear to be mutually exclusive, suggesting that distinct pools of N-terminal cysteine proteins may be acetylated or oxidised. These results reveal the sequence determinants that contribute to N-terminal cysteine protein modifications, with implications for O-dependent protein stability and the hypoxic response.
Topics: Cysteine; Acetylation; Humans; Oxidation-Reduction; Protein Stability; Oxygen; Protein Processing, Post-Translational; Amino Acid Sequence; HEK293 Cells
PubMed: 38918375
DOI: 10.1038/s41467-024-49489-2