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Microorganisms Jun 2024Malaria parasites increase their host erythrocyte's permeability to obtain essential nutrients from plasma and facilitate intracellular growth. In the human pathogen,...
Malaria parasites increase their host erythrocyte's permeability to obtain essential nutrients from plasma and facilitate intracellular growth. In the human pathogen, this increase is mediated by the plasmodial surface anion channel (PSAC) and has been linked to CLAG3, a protein integral to the host erythrocyte membrane and encoded by a member of the conserved multigene family. Whether paralogs encoded by other genes also insert at the host membrane is unknown; their contributions to PSAC formation and other roles served are also unexplored. Here, we generated transfectant lines carrying epitope-tagged versions of each CLAG. Each paralog is colocalized with CLAG3, with concordant trafficking via merozoite rhoptries to the host erythrocyte membrane of newly invaded erythrocytes. Each also exists within infected cells in at least two forms: an alkaline-extractable soluble form and a form integral to the host membrane. Like CLAG3, CLAG2 has a variant region cleaved by extracellular proteases, but CLAG8 and CLAG9 are protease resistant. Paralog knockout lines, generated through CRISPR/Cas9 transfection, exhibited uncompromised growth in PGIM, a modified medium with higher physiological nutrient levels; this finding is in marked contrast to a recently reported CLAG3 knockout parasite. CLAG2 and CLAG8 knockout lines exhibited compensatory increases in the transcription of the remaining and associated genes, yielding increased PSAC-mediated uptake for specific solutes. We also report on the distinct transport properties of these knockout lines. Similar membrane topologies at the host membrane are consistent with each CLAG paralog contributing to PSAC, but other roles require further examination.
PubMed: 38930554
DOI: 10.3390/microorganisms12061172 -
Journal of Personalized Medicine Jun 2024The ATP-binding cassette (ABC) transporters are a vast group of 48 membrane proteins, some of which are of notable physiological and clinical importance. Some ABC... (Review)
Review
The ATP-binding cassette (ABC) transporters are a vast group of 48 membrane proteins, some of which are of notable physiological and clinical importance. Some ABC transporters are involved in functions such as the transport of chloride ions, bilirubin, reproductive hormones, cholesterol, and iron. Consequently, genetic or physiological disruption in these functions is manifested in various disease processes like cystic fibrosis, Tangier disease, and sideroblastic anemia. Among other etiologies, primary sideroblastic anemia results from a genetic mutation in the ATP-binding cassette-7 (ABCB7), a member of the ABC transporter family. There are not many articles specifically tackling the disease processes caused by ABC transporters in detail. Some testing methodologies previously reported in the available literature for investigating sideroblastic anemia need updating. Here, we expound on the relevance of ABCB7 as a clinically important ABC transporter and a rare participant in the disease process of Sideroblastic anemia. The other genetic and secondary etiologies of sideroblastic anemia, which do not involve mutations in the ABCB7 protein, are also described. We review the pathophysiology, clinical course, symptoms, diagnosis, and treatment of sideroblastic anemia with a focus on modern technologies for laboratory testing.
PubMed: 38929857
DOI: 10.3390/jpm14060636 -
Animals : An Open Access Journal From... Jun 2024The present study aimed to investigate the impacts of dietary standardized ileal digestible lysine to net energy (SID Lys:NE) ratio on lipid metabolism in pigs fed...
The present study aimed to investigate the impacts of dietary standardized ileal digestible lysine to net energy (SID Lys:NE) ratio on lipid metabolism in pigs fed high-wheat diets. Thirty-six crossbred growing barrows (65.20 ± 0.38 kg) were blocked into two treatment groups, fed high-wheat diets with either a high SID Lys:NE ratio (HR) or a low SID Lys:NE ratio (LR). Each treatment group consisted of three replicates, with six pigs per pen in each replicate. The diminishing dietary SID Lys:NE ratio exhibited no adverse impacts on the carcass trait ( > 0.05) but increased the marbling score of the longissimus dorsi muscle ( < 0.05). Meanwhile, LR diets tended to increase the serum triglyceride concentration ( < 0.1). LR diets upregulated fatty acid transport protein 4 and acetyl-coA carboxylase α expression levels and downregulated the expression level of adipose triglyceride lipase ( < 0.05). LR diets improved energy metabolism via decreasing the expression levels of AMP-activated protein kinase (AMPK) α1, sirtuin 1 (SIRT1), and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) ( < 0.05). Additionally, LR diets stimulated hepatic bile acid synthesis via upregulating the expression levels of cytochrome P450 family 7 subfamily A member 1 and cytochrome P450 family 27 subfamily A member 1, and downregulating farnesol X receptor (FXR) and small heterodimer partner (SHP) expression levels ( < 0.05). A lowered SID Lys:NE ratio affected the colonic microbial composition, characterized by increased relative abundances of , , , and , alongside a decreased in the proportion of , , , , , , , , and ( < 0.05). The alterations in microbial composition were accompanied by a decrease in colonic butyrate concentration ( < 0.1). The metabolomic analysis revealed that LR diets affected primary bile acid synthesis and AMPK signaling pathway ( < 0.05). And the mantel analysis indicated that , , , , and contributed to the alterations in body metabolism. A reduced dietary SID Lys:NE ratio improves energy metabolism, stimulates lipogenesis, and inhibits lipolysis in finishing pigs by regulating the AMPKα/SIRT1/PGC-1α pathway and the FXR/SHP pathway. and benefited bile acids synthesis, whereas , , and may contribute to the activation of the AMPK signaling pathway. Overall, body metabolism and colonic microbiota collectively controlled the lipid metabolism in finishing pigs.
PubMed: 38929443
DOI: 10.3390/ani14121824 -
Antioxidants (Basel, Switzerland) Jun 2024Starch is a common source of carbohydrates in aqua feed. High-starch diet can cause hepatic injury and lipid accumulation in fish. Mangiferin (MGF) can regulate lipid...
Supplementation of Mangiferin to a High-Starch Diet Alleviates Hepatic Injury and Lipid Accumulation Potentially through Modulating Cholesterol Metabolism in Channel Catfish ().
Starch is a common source of carbohydrates in aqua feed. High-starch diet can cause hepatic injury and lipid accumulation in fish. Mangiferin (MGF) can regulate lipid metabolism and protect the liver, but there is limited research on its effects in fish. In the present study, we investigated whether MGF could ameliorate high-starch-induced hepatic damage and lipid accumulation in channel catfish. The channel catfish () were fed one of four experimental diets for eight weeks: a control diet (NCD), a high-starch diet (HCD), an HCD supplemented with 100 mg/kg MGF (100 MGF), and an HCD supplemented with 500 mg/kg MGF (500 MGF). The results demonstrated that the weight gain rate (WGR) ( = 0.031), specific growth rate (SGR) ( = 0.039), and feed conversion efficiency (FCE) ( = 0.040) of the 500 MGF group were significantly higher than those of the NCD group. MGF supplementation alleviated liver damage and improved antioxidant capacity (T-AOC) compared to those of the HCD group ( = 0.000). In addition, dietary MGF significantly reduced plasma glucose (GLU) ( = 0.000), triglyceride (TG) (= 0.001), and low-density lipoprotein cholesterol (LDL) ( = 0.000) levels. It is noteworthy that MGF significantly reduced the plasma total cholesterol (TC) levels ( = 0.000) and liver TC levels ( = 0.005) of channel catfish. Dietary MGF improves cholesterol homeostasis by decreasing the expression of genes that are involved in cholesterol synthesis and transport (, , , , and ) and increasing the expression of genes that are involved in cholesterol catabolism (). Among them, the largest fold decrease in squalene epoxidase (sqle) expression levels was observed in the 100 MGF or 500 MGF groups compared with the HCD group, with a significant decrease of 3.64-fold or 2.20-fold ( = 0.008). And the 100 MGF or 500 MGF group had significantly decreased (by 1.67-fold or 1.94-fold) Sqle protein levels compared to those of the HCD group ( = 0.000). In primary channel catfish hepatocytes, MGF significantly down-regulated the expression of ( = 0.030) and reduced cholesterol levels ( = 0.000). In NCTC 1469 cells, MGF significantly down-regulated the expression of sqle ( = 0.000) and reduced cholesterol levels ( = 0.024). In conclusion, MGF effectively inhibits sqle expression and reduces cholesterol accumulation. The current study shows how MGF supplementation regulates the metabolism and accumulation of cholesterol in channel catfish, providing a theoretical basis for the use of MGF as a dietary supplement in aquaculture.
PubMed: 38929161
DOI: 10.3390/antiox13060722 -
Foods (Basel, Switzerland) Jun 2024Silicon included in a restructured meat (RM) matrix (Si-RM) as a functional ingredient has been demonstrated to be a potential bioactive antidiabetic compound. However,...
Silicon included in a restructured meat (RM) matrix (Si-RM) as a functional ingredient has been demonstrated to be a potential bioactive antidiabetic compound. However, the jejunal and hepatic molecular mechanisms by which Si-RM exerts its cholesterol-lowering effects remain unclear. Male Wistar rats fed an RM included in a high-saturated-fat high-cholesterol diet (HSFHCD) combined with a low dose of streptozotocin plus nicotinamide injection were used as late-stage type 2 diabetes mellitus (T2DM) model. Si-RM was included into the HSFHCD as a functional food. An early-stage TD2M group fed a high-saturated-fat diet (HSFD) was taken as reference. Si-RM inhibited the hepatic and intestinal microsomal triglyceride transfer protein (MTP) reducing the apoB-containing lipoprotein assembly and cholesterol absorption. Upregulation of liver X receptor (LXRα/β) by Si-RM turned in a higher low-density lipoprotein receptor (LDLr) and ATP-binding cassette transporters (ABCG5/8, ABCA1) promoting jejunal cholesterol efflux and transintestinal cholesterol excretion (TICE), and facilitating partially reverse cholesterol transport (RCT). Si-RM decreased the jejunal absorptive area and improved mucosal barrier integrity. Consequently, plasma triglycerides and cholesterol levels decreased, as well as the formation of atherogenic lipoprotein particles. Si-RM mitigated the dyslipidemia associated with late-stage T2DM by Improving cholesterol homeostasis. Silicon could be used as an effective nutritional approach in diabetic dyslipidemia management.
PubMed: 38928736
DOI: 10.3390/foods13121794 -
International Journal of Molecular... Jun 2024Genetic insights help us to investigate disease pathogenesis and risk. The ABCA1 protein encoded by is involved in transporting cholesterol across the cell membrane....
Genetic insights help us to investigate disease pathogenesis and risk. The ABCA1 protein encoded by is involved in transporting cholesterol across the cell membrane. Genetic variations in the gene are well documented; however, their role in the development of diabetic dyslipidemia still needs to be explored. This study aimed to identify the associations of rs757194699 (K1587Q) and rs2066714 (I883M) with dyslipidemia in type 2 diabetes and performed molecular simulations. In our case-control study, 330 individuals were divided equally into a diabetic dyslipidemia cases and a healthy controls. Allele-specific polymerase chain reaction and restriction fragment length polymorphism were performed to screen selected variants of the gene. Sanger sequencing was also performed to find genetic mutations in exon 5 of the gene. The C allele of rs757194699 was observed at a high frequency in cases compared to controls and followed the overdominant genetic model ( < 0.0001, OR:3.84; CI:1.67-8.82). The frequency of G allele of rs2066714 was significantly higher in cases compared to controls and followed the genetic model of codominant (< 0.0001, OR: 39.61; CI:9.97-157.32), dominant ( < 0.0001,OR:59.59; CI:15.19-233.81), overdominant (< 0.0001, OR:9.75; CI:3.16-30.11), and log-additive (< 0.0001, OR:42.15; CI:11.08-160.40). In silico modeling and docking revealed that rs2066714 and rs757194699 produced deleterious conformational changes in the ABCA1 protein, resulting in alterations in the binding of the apoA1 protein. There were no genetic variations found in exon-5 in Sanger sequencing. The G allele of rs2066714 and C allele of rs757194699 in the gene were found to be risk alleles in the development of dyslipidemia in type 2 diabetes. These polymorphisms could alter the binding site of ABCA1 with apoA1 thus disturbs the reverse cholesterol transport.
Topics: Humans; Diabetes Mellitus, Type 2; ATP Binding Cassette Transporter 1; Dyslipidemias; Genetic Predisposition to Disease; Male; Female; Middle Aged; Polymorphism, Single Nucleotide; Case-Control Studies; Alleles; Gene Frequency; Aged; Molecular Docking Simulation
PubMed: 38928502
DOI: 10.3390/ijms25126796 -
International Journal of Molecular... Jun 2024Phytaspases differ from other members of the plant subtilisin-like protease family by having rare aspartate cleavage specificity and unusual localization dynamics....
Phytaspases differ from other members of the plant subtilisin-like protease family by having rare aspartate cleavage specificity and unusual localization dynamics. Phytaspases are secreted from healthy plant cells but are re-internalized upon perception of death-inducing stresses. Although proteolytic activity is required for the secretion of plant subtilases, its requirement for the retrograde transportation of phytaspases is currently unknown. To address this issue, we employed an approach to complement in trans the externalization of a prodomain-less form of phytaspase (Phyt) with the free prodomain in leaf cells. Using this approach, the generation of the proteolytically active Phyt and its transport to the extracellular space at a level comparable to that of the native Phyt (synthesized as a canonical prodomain-containing precursor protein) were achieved. The application of this methodology to Phyt with a mutated catalytic Ser537 residue resulted in the secretion of the inactive, although processed (prodomain-free), protein as well. Notably, the externalized Phyt Ser537Ala mutant was still capable of retrograde transportation into plant cells upon the induction of oxidative stress. Our data thus indicate that the proteolytic activity of Phyt is dispensable for stress-induced retrograde transport of the enzyme.
Topics: Nicotiana; Proteolysis; Plant Proteins; Oxidative Stress; Stress, Physiological; Subtilisins; Plant Leaves; Protein Transport
PubMed: 38928451
DOI: 10.3390/ijms25126729 -
International Journal of Molecular... Jun 2024During the adaptive evolution of animals, the host and its gut microbiota co-adapt to different elevations. Currently, there are few reports on the rumen...
During the adaptive evolution of animals, the host and its gut microbiota co-adapt to different elevations. Currently, there are few reports on the rumen microbiota-hepato-intestinal axis of Tibetan sheep at different altitudes. Therefore, the purpose of this study was to explore the regulatory effect of rumen microorganism-volatile fatty acids (VFAs)-VFAs transporter gene interactions on the key enzymes and genes related to gluconeogenesis in Tibetan sheep. The rumen fermentation parameters, rumen microbial densities, liver gluconeogenesis activity and related genes were determined and analyzed using gas chromatography, RT-qPCR and other research methods. Correlation analysis revealed a reciprocal relationship among rumen microflora-VFAs-hepatic gluconeogenesis in Tibetan sheep at different altitudes. Among the microbiota, (), (), and () were significantly correlated with propionic acid ( < 0.05), while propionic acid was significantly correlated with the transport genes monocarboxylate transporter 4 () and anion exchanger 2 () ( < 0.05). Propionic acid was significantly correlated with key enzymes such as pyruvate carboxylase, phosphoenolpyruvic acid carboxylase and glucose (Glu) in the gluconeogenesis pathway ( < 0.05). Additionally, the expressions of these genes were significantly correlated with those of the related genes, namely, forkhead box protein O1 () and mitochondrial phosphoenolpyruvate carboxykinase 2 () ( < 0.05). The results showed that rumen microbiota densities differed at different altitudes, and the metabolically produced VFA contents differed, which led to adaptive changes in the key enzyme activities of gluconeogenesis and the expressions of related genes.
Topics: Animals; Gluconeogenesis; Sheep; Rumen; Gastrointestinal Microbiome; Liver; Fatty Acids, Volatile; Tibet; Altitude; Adaptation, Physiological; Fermentation
PubMed: 38928432
DOI: 10.3390/ijms25126726 -
International Journal of Molecular... Jun 2024Water deficit is the major stress factor magnified by climate change that causes the most reductions in plant productivity. Knowledge of photosystem II (PSII) response...
Water deficit is the major stress factor magnified by climate change that causes the most reductions in plant productivity. Knowledge of photosystem II (PSII) response mechanisms underlying crop vulnerability to drought is critical to better understanding the consequences of climate change on crop plants. Salicylic acid (SA) application under drought stress may stimulate PSII function, although the exact mechanism remains essentially unclear. To reveal the PSII response mechanism of celery plants sprayed with water (WA) or SA, we employed chlorophyll fluorescence imaging analysis at 48 h, 96 h, and 192 h after watering. The results showed that up to 96 h after watering, the stroma lamellae of SA-sprayed leaves appeared dilated, and the efficiency of PSII declined, compared to WA-sprayed plants, which displayed a better PSII function. However, 192 h after watering, the stroma lamellae of SA-sprayed leaves was restored, while SA boosted chlorophyll synthesis, and by ameliorating the osmotic potential of celery plants, it resulted in higher relative leaf water content compared to WA-sprayed plants. SA, by acting as an antioxidant under drought stress, suppressed phototoxicity, thereby offering PSII photoprotection, together with enhanced effective quantum yield of PSII photochemistry (Φ) and decreased quantity of singlet oxygen (O) generation compared to WA-sprayed plants. The PSII photoprotection mechanism induced by SA under drought stress was triggered by non-photochemical quenching (NPQ), which is a strategy to protect the chloroplast from photo-oxidative damage by dissipating the excess light energy as heat. This photoprotective mechanism, triggered by NPQ under drought stress, was adequate in keeping, especially in high-light conditions, an equal fraction of open PSII reaction centers (q) as of non-stress conditions. Thus, under water deficit stress, SA activates a regulatory network of stress and light energy partitioning signaling that can mitigate, to an extent, the water deficit stress on PSII functioning.
Topics: Photosystem II Protein Complex; Salicylic Acid; Plant Leaves; Chlorophyll; Apium; Droughts; Water; Photosynthesis; Dehydration; Stress, Physiological
PubMed: 38928427
DOI: 10.3390/ijms25126721 -
International Journal of Molecular... Jun 2024The SLC35 (Solute Carrier 35) family members acting as nucleotide sugar transporters are typically localized in the endoplasmic reticulum or Golgi apparatus. It is,...
The SLC35 (Solute Carrier 35) family members acting as nucleotide sugar transporters are typically localized in the endoplasmic reticulum or Golgi apparatus. It is, therefore, intriguing that some reports document the presence of orphan transporters SLC35F1 and SLC35F6 within the endosomal and lysosomal system. Here, we compared the subcellular distribution of these proteins and found that they are concentrated in separate compartments; i.e., recycling endosomes for SLC35F1 and lysosomes for SLC35F6. Swapping the C-terminal tail of these proteins resulted in a switch of localization, with SLC35F1 being trafficked to lysosomes while SLC35F6 remained in endosomes. This suggested the presence of specific sorting signals in these C-terminal regions. Using site-directed mutagenesis, fluorescence microscopy, and cell surface biotinylation assays, we found that the EQERLL signal located in the cytoplasmic tail of human SLC35F6 is involved in its lysosomal sorting (as previously shown for this conserved sequence in mouse SLC35F6), and that SLC35F1 localization in the recycling pathway depends on two YXXΦ-type signals: a YKQF sequence facilitates its internalization from the plasma membrane, while a YTSL motif prevents its transport to lysosomes, likely by promoting SLC35F1 recycling to the cell surface. Taken together, these results support that some SLC35 members may function at different levels of the endosomal and lysosomal system.
Topics: Lysosomes; Endosomes; Humans; Protein Transport; Animals; Nucleotide Transport Proteins; HeLa Cells; Mice; Golgi Apparatus; Amino Acid Sequence; Protein Sorting Signals; HEK293 Cells; Cell Membrane
PubMed: 38928424
DOI: 10.3390/ijms25126718