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Experimental and Therapeutic Medicine Jul 2024Particulate matter 2.5 (PM) imposes a heavy burden on the skin and respiratory system of human beings, causing side effects such as aging, inflammation and cancer....
Particulate matter 2.5 (PM) imposes a heavy burden on the skin and respiratory system of human beings, causing side effects such as aging, inflammation and cancer. Astaxanthin (ATX) is a well-known antioxidant widely used for its anti-inflammatory and anti-aging properties. However, few studies have investigated the protective effects of ATX against PM-induced senescence in HaCaT cells. In the present study, the levels of reactive oxygen species (ROS) and antioxidant enzymes were measured after treatment with PM. The results revealed that PM generated excessive ROS and reduced the translocation of nuclear factor erythroid 2-related factor 2 (NRF2), subsequently reducing the expression of antioxidant enzymes. However, pretreatment with ATX reversed the ROS levels as well as the expression of antioxidant enzymes. In addition, ATX protected cells from PM-induced DNA damage and rescued PM-induced cell cycle arrest. The levels of senescence-associated phenotype markers, such as interleukin-1β, matrix metalloproteinases, and β-galactosidase, were increased by exposure to PM, however these effects were reversed by ATX. After interfering with NRF2 mRNA expression and exposing cells to PM, the levels of ROS and β-galactosidase were higher compared with siControl RNA cells exposed to PM. However, ATX inhibited ROS and β-galactosidase levels in both the siControl RNA and the siNRF2 RNA groups. Thus, ATX protects HaCaT keratinocytes from PM-induced senescence by partially inhibiting excessive ROS generation via the NRF2 signaling pathway.
PubMed: 38800049
DOI: 10.3892/etm.2024.12563 -
Plants (Basel, Switzerland) May 2024Carotenoids are valuable pigments naturally occurring in all photosynthetic plants and microalgae as well as in selected fungi, bacteria, and archaea. Green microalgae...
Carotenoids are valuable pigments naturally occurring in all photosynthetic plants and microalgae as well as in selected fungi, bacteria, and archaea. Green microalgae developed a complex carotenoid profile suitable for efficient light harvesting and light protection and harbor great capacity for carotenoid production through the substantial power of the endogenous 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway. Previous works established successful genome editing and induced significant changes in the cellular carotenoid content in . This study employs a tailored carotenoid pathway for engineered bioproduction of the valuable ketocarotenoid astaxanthin. Functional knockout of lycopene ε-cyclase (LCYE) and non-homologous end joining (NHEJ)-based integration of donor DNA at the target site inhibit the accumulation of α-carotene and consequently lutein and loroxanthin, abundant carotenoids in without changes in cellular fitness. PCR-based screening indicated that 4 of 96 regenerated candidate lines carried (partial) integrations of donor DNA and increased ß-carotene as well as derived carotenoid contents. Iterative overexpression of BKT, crtB, and CHYB resulted in a 2.3-fold increase in astaxanthin accumulation in mutant ΔLCYE#3 (1.8 mg/L) compared to the parental strain UVM4, which demonstrates the potential of genome editing for the design of a green cell factory for astaxanthin bioproduction.
PubMed: 38794462
DOI: 10.3390/plants13101393 -
Life (Basel, Switzerland) Apr 2024(1) Background: Oxygen has exerted a great effect in shaping the environment and driving biological diversity in Earth's history. Green lineage has evolved primary and...
(1) Background: Oxygen has exerted a great effect in shaping the environment and driving biological diversity in Earth's history. Green lineage has evolved primary and secondary carotenoid biosynthetic systems to adapt to Earth's oxygenation, e.g., , which accumulates the highest amount of secondary astaxanthin under stresses. The two systems are controlled by lycopene ε-cyclase (LCYE) and β-cyclase (LCYB), which leave an important trace in Earth's oxygenation. (2) Objectives: This work intends to disclose the underlying molecular evolutionary mechanism of Earth's oxygenation in shaping green algal carotenogensis with a special focus on lycopene cyclases. (3) Methods: The two kinds of cyclases were analyzed by site-directed mutagenesis, phylogeny, divergence time and functional divergence. (4) Results: Green lineage LCYEs appeared at ~1.5 Ga after the first significant appearance and accumulation of atmospheric oxygen, the so-called Great Oxygenation Event (GOE), from which LCYBs diverged by gene duplication. Bacterial β-bicyclases evolved from β-monocyclase. Enhanced catalytic activity accompanied evolutionary transformation from ε-/β-monocyclase to β-bicyclase. Strong positive selection occurred in green lineage LCYEs after the GOE and in algal LCYBs during the second oxidation, the Neoproterozoic Oxygenation Event (NOE). Positively selected sites in the catalytic cavities of the enzymes controlled the mono-/bicyclase activity, respectively. Carotenoid profiling revealed that oxidative adaptation has been wildly preserved in evolution. (5) Conclusions: the functionalization of the two enzymes is a result of primary to secondary adaptations to Earth's oxygenation.
PubMed: 38792597
DOI: 10.3390/life14050576 -
International Journal of Molecular... May 2024Extracellular vesicles (EVs) are nano-sized particles involved in intercellular communications that intrinsically possess many attributes as a modern drug delivery... (Comparative Study)
Comparative Study
Extracellular vesicles (EVs) are nano-sized particles involved in intercellular communications that intrinsically possess many attributes as a modern drug delivery platform. -derived EVs (HpEVs) can be potentially exploited as a high-value-added bioproduct during astaxanthin production. The encapsulation of HpEV cargo is a crucial key for the determination of their biological functions and therapeutic potentials. However, little is known about the composition of HpEVs, limiting insights into their biological properties and application characteristics. This study examined the protein composition of HpEVs from three growth phases of grown under high light (350 µmol·m·s) and sodium acetate (45 mM) stresses. A total of 2038 proteins were identified, the majority of which were associated with biological processes including signal transduction, cell proliferation, cell metabolism, and the cell response to stress. Comparative analysis indicated that cells sort variant proteins into HpEVs at different physiological states. It was revealed that HpEVs from the early growth stage of contain more proteins associated with cellular functions involved in primary metabolite, cell division, and cellular energy metabolism, while HpEVs from the late growth stage of were enriched in proteins involved in cell wall synthesis and secondary metabolism. This is the first study to report and compare the protein composition of HpEVs from different growth stages of , providing important information on the development and production of functional microalgal-derived EVs.
Topics: Extracellular Vesicles; Proteome; Sodium Acetate; Light; Proteomics; Stress, Physiological; Chlorophyceae; Chlorophyta
PubMed: 38791459
DOI: 10.3390/ijms25105421 -
Antioxidants (Basel, Switzerland) Apr 2024Various antioxidants are tested to improve the viability and development of cryopreserved oocytes, due to their known positive health effects. The aim of this study was...
Various antioxidants are tested to improve the viability and development of cryopreserved oocytes, due to their known positive health effects. The aim of this study was to find whether astaxanthin (AX), a xanthophyll carotenoid, could mitigate deteriorations that occurred during the vitrification/warming process in bovine oocytes. Astaxanthin (2.5 µM) was added to the maturation medium during the post-warm recovery period of vitrified oocytes for 3 h. Afterward, the oocytes were fertilized in vitro using frozen bull semen and presumptive zygotes were cultured in the B2 Menezo medium in a co-culture with BRL-1 cells at 38.5 °C and 5% CO until the blastocyst stage. AX addition significantly reduced ROS formation, lipid peroxidation, and lysosomal activity, while increasing mitochondrial activity in vitrified oocytes. Although the effect of AX on embryo development was not observed, it stimulated cell proliferation in the blastocysts derived from vitrified oocytes and improved their quality by upregulation or downregulation of some genes related to apoptosis (, ), oxidative stress (, ), and development () compared to the vitrified group without AX. Therefore, the antioxidant properties of astaxanthin even during short exposure to bovine vitrified/warmed oocytes resulted in improved blastocyst quality comparable to those from fresh oocytes.
PubMed: 38790660
DOI: 10.3390/antiox13050556 -
Antioxidants (Basel, Switzerland) Apr 2024This study aimed to assess the influence of varying dietary levels of astaxanthin (AST) on the growth, antioxidant capacity and lipid metabolism of juvenile swimming...
This study aimed to assess the influence of varying dietary levels of astaxanthin (AST) on the growth, antioxidant capacity and lipid metabolism of juvenile swimming crabs. Six diets were formulated to contain different AST levels, and the analyzed concentration of AST in experimental diets were 0, 24.2, 45.8, 72.4, 94.2 and 195.0 mg kg, respectively. Juvenile swimming crabs (initial weight 8.20 ± 0.01 g) were fed these experimental diets for 56 days. The findings indicated that the color of the live crab shells and the cooked crab shells gradually became red with the increase of dietary AST levels. Dietary 24.2 mg kg astaxanthin significantly improved the growth performance of swimming crab. the lowest activities of glutathione (GSH), total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and peroxidase (POD) were found in crabs fed without AST supplementation diet. Crabs fed diet without AST supplementation showed lower lipid content and the activity of fatty acid synthetase (FAS) in hepatopancreas than those fed diets with AST supplementation, however, lipid content in muscle and the activity of carnitine palmitoyl transferase (CPT) in hepatopancreas were not significantly affected by dietary AST levels. And it can be found in oil red O staining that dietary 24.2 and 45.8 mg kg astaxanthin significantly promoted the lipid accumulation of hepatopancreas. Crabs fed diet with 195.0 mg kg AST exhibited lower expression of , , , and in hepatopancreas than those fed the other diets, however, the expression of genes related to antioxidant such as , , , and in hepatopancreas significantly down-regulated with the increase of dietary AST levels. In conclusion, dietary 24.2 and 45.8 mg kg astaxanthin significantly promoted the lipid accumulation of hepatopancreas and im-proved the antioxidant and immune capacity of hemolymph.
PubMed: 38790627
DOI: 10.3390/antiox13050522 -
Antioxidants (Basel, Switzerland) Apr 2024Astaxanthin (AST), functioning as an efficient antioxidant and pigment, is one of the most expensive additives in shrimp feeds. How to improve the uptake efficiency of...
Astaxanthin (AST), functioning as an efficient antioxidant and pigment, is one of the most expensive additives in shrimp feeds. How to improve the uptake efficiency of dietary astaxanthin into farmed shrimp is of significance. The present study investigated the effects of lysophosphatidylcholine (LPC), an emulsifier, on dietary astaxanthin efficiency, growth performance, body color, body composition, as well as lipid metabolism of juvenile Pacific white shrimp (average initial body weight: 2.4 g). Three diets were prepared: control group, the AST group (supplemented with 0.02% AST), and the AST + LPC group (supplemented with 0.02% AST and 0.1% LPC). Each diet was fed to triplicate tanks, and each tank was stocked with 30 shrimp. The shrimp were fed four times daily for eight weeks. The AST supplementation improved the growth of white shrimp, while LPC further promoted the final weight of shrimp, but the whole-shrimp proximate composition and fatty acid composition were only slightly affected by AST and LPC. The LPC supplementation significantly increased the astaxanthin deposition in the muscle. The LPC supplementation significantly increased the shell yellowness of both raw and cooked shrimp compared to the AST group. Moreover, the dietary LPC increased the high-density lipoprotein-cholesterol content but decreased the low-density lipoprotein-cholesterol content in the serum, indicating the possible regulation of lipid and cholesterol transport. The addition of astaxanthin significantly up-regulated the expression of in the hepatopancreas compared to the control group, while the addition of LPC down-regulated the expression of compared to the AST group. In conclusion, the LPC supplementation could facilitate the deposition of dietary astaxanthin into farmed shrimp and further enlarge the beneficial effects of dietary astaxanthin. LPC may also independently regulate shrimp body color and cholesterol transportation. This was the first investigation of the promoting effects of LPC on dietary astaxanthin efficiency.
PubMed: 38790610
DOI: 10.3390/antiox13050505 -
Molecular Metabolism Jul 2024Aggregation and misfolding of amyloid beta (Aβ) and tau proteins, suggested to arise from post-translational modification processes, are thought to be the main cause of...
OBJECTIVES
Aggregation and misfolding of amyloid beta (Aβ) and tau proteins, suggested to arise from post-translational modification processes, are thought to be the main cause of Alzheimer's disease (AD). Additionally, a plethora of evidence exists that links metabolic dysfunctions such as obesity, type 2 diabetes (T2D), and dyslipidemia to the pathogenesis of AD. We thus investigated the combinatory effect of T2D and human glutaminyl cyclase activity (pyroglutamylation), on the pathology of AD and whether astaxanthin (ASX) treatment ameliorates accompanying pathophysiological manifestations.
METHODS
Male transgenic AD mice, APPxhQC, expressing human APP751 with the Swedish and the London mutation and human glutaminyl cyclase (hQC) enzyme and their non-transgenic (NTG) littermates were used. Both APPxhQC and NTG mice were allocated to 3 groups, control, T2D-control, and T2D-ASX. Mice were fed control or high fat diet ± ASX for 13 weeks starting at an age of 11-12 months. High fat diet fed mice were further treated with streptozocin for T2D induction. Effects of genotype, T2D induction, and ASX treatment were evaluated by analysing glycemic readouts, lipid concentration, Aβ deposition, hippocampus-dependent cognitive function and nutrient sensing using immunosorbent assay, ELISA-based assays, western blotting, immunofluorescence staining, and behavioral testing via Morris water maze (MWM), respectively.
RESULTS
APPxhQC mice presented a higher glucose sensitivity compared to NTG mice. T2D-induced brain dysfunction was more severe in NTG compared to the APPxhQC mice. T2D induction impaired memory functions while increasing hepatic LC3B, ABCA1, and p65 levels in NTG mice. T2D induction resulted in a progressive shift of Aβ from the soluble to insoluble form in APPxhQC mice. ASX treatment reversed T2D-induced memory dysfunction in NTG mice and in parallel increased hepatic pAKT while decreasing p65 and increasing cerebral p-S6rp and p65 levels. ASX treatment reduced soluble Aβ38 and Aβ40 and insoluble Aβ40 levels in T2D-induced APPxhQC mice.
CONCLUSIONS
We demonstrate that T2D induction in APPxhQC mice poses additional risk for AD pathology as seen by increased Aβ deposition. Although ASX treatment reduced Aβ expression in T2D-induced APPxhQC mice and rescued T2D-induced memory impairment in NTG mice, ASX treatment alone may not be effective in cases of T2D comorbidity and AD.
Topics: Animals; Mice, Transgenic; Diabetes Mellitus, Type 2; Mice; Xanthophylls; Male; Alzheimer Disease; Humans; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Diet, High-Fat; Mice, Inbred C57BL
PubMed: 38763496
DOI: 10.1016/j.molmet.2024.101959 -
Journal of Orthopaedic Surgery and... May 2024Osteonecrosis of the femoral head caused by glucocorticoids (GIONFH) is a significant issue resulting from prolonged or excessive clinical glucocorticoid use....
Astaxanthin-mediated Nrf2 activation ameliorates glucocorticoid-induced oxidative stress and mitochondrial dysfunction and impaired bone formation of glucocorticoid-induced osteonecrosis of the femoral head in rats.
BACKGROUND
Osteonecrosis of the femoral head caused by glucocorticoids (GIONFH) is a significant issue resulting from prolonged or excessive clinical glucocorticoid use. Astaxanthin, an orange-red carotenoid present in marine organisms, has been the focus of this study to explore its impact and mechanism on osteoblast apoptosis induced by dexamethasone (Dex) and GIONFH.
METHODS
In this experiment, bioinformatic prediction, molecular docking and dynamics simulation, cytotoxicity assay, osteogenic differentiation, qRT-PCR analysis, terminal uridine nickend labeling (TUNEL) assay, determination of intracellular ROS, mitochondrial function assay, immunofluorescence, GIONFH rat model construction, micro-computed tomography (micro-CT) scans were performed.
RESULTS
Our research demonstrated that a low dose of astaxanthin was non-toxic to healthy osteoblasts and restored the osteogenic function of Dex-treated osteoblasts by reducing oxidative stress, mitochondrial dysfunction, and apoptosis. Furthermore, astaxanthin rescued the dysfunction in poor bone quality, bone metabolism and angiogenesis of GIONFH rats. The mechanism behind this involves astaxanthin counteracting Dex-induced osteogenic damage by activating the Nrf2 pathway.
CONCLUSION
Astaxanthin shields osteoblasts from glucocorticoid-induced oxidative stress and mitochondrial dysfunction via Nrf2 pathway activation, making it a potential therapeutic agent for GIONFH treatment.
Topics: Animals; Xanthophylls; Oxidative Stress; NF-E2-Related Factor 2; Glucocorticoids; Femur Head Necrosis; Osteogenesis; Mitochondria; Rats; Osteoblasts; Male; Dexamethasone; Rats, Sprague-Dawley; Apoptosis; Disease Models, Animal
PubMed: 38745231
DOI: 10.1186/s13018-024-04775-z -
Frontiers in Microbiology 2024Abiotic stresses can increase the total fatty acid (TFA) and astaxanthin accumulation in microalgae. However, it remains unknown whether a unified signal transduction...
Abiotic stresses can increase the total fatty acid (TFA) and astaxanthin accumulation in microalgae. However, it remains unknown whether a unified signal transduction mechanism exists under different stresses. This study explored the link between nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived reactive oxygen species (ROS) and the accumulation of fatty acids and astaxanthin in under three abiotic stresses. Results showed significant increases in fatty acid, astaxanthin, and ROS levels under nitrogen deficiency, phosphorus deficiency, and high-salinity stress. The introduction of the NADPH oxidase inhibitor diphenyleneiodonium (DPI) decreased the content of these components. This underscores the pivotal role of NADPH oxidase-derived ROS in the accumulation of fatty acid and astaxanthin under abiotic stress. Analysis of transcriptomes across three conditions following DPI addition revealed 1,445 shared differentially expressed genes (DEGs). Enrichment analysis revealed that biotin, betalain, thiamine, and glucosinolate may be important in stress responses. The heatmap demonstrated that DPI notably suppressed gene expression in the fatty acid and carotenoid biosynthesis pathways. Our findings underscore the pivotal role of NADPH oxidase-derived ROS in the accumulation of fatty acid and astaxanthin under abiotic stresses.
PubMed: 38741732
DOI: 10.3389/fmicb.2024.1387222