FISH & SHELLFISH IMMUNOLOGY
·
2023
·
IF 4.7
Yihan Yu,Dandan Tian,Sanghyok Ri,Tongchol Kim,Kwangjin Ju,Jiongming Zhang,Shuangshuang Teng,Weixia Zhang,Wei Shi,Guangxu Liu
Although accumulating data demonstrated that gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter , plays an important regulatory role in immunity of vertebrates, its immunomodulatory function and mechanisms of action remain poorly understood in invertebrates such as bivalve mollusks . In this study, the effect of GABA on phagocytic activity of hemocytes was evaluated in a commercial bivalve species, Tegillarca granosa . Furthermore, the potential regulatory mechanism underpinning was investigated by assessing potential downstream targets. Data obtained demonstrated that in vitro GABA incubation significantly constrained the phagocytic activity of hemocytes. In addition, the GABA-induced suppression of phagocytosis was markedly relieved by blocking of GABA A and GABA B receptors using corresponding antagonists. Hemocytes incubated with lipopolysaccharides (LPS) and GABA had significant higher K + -Cl - cotransporter 2 (KCC2) content compared to the control. In addition, GABA treatment led to an elevation in intracellular Cl − , which was shown to be leveled down to normal by blocking the ionotropic GABA A receptor. Treatment with GABA A receptor antagonist also rescued the suppression of GABA A receptor-associated protein ( GABARAP ), KCC , TNF receptor associated factor 6 ( TRAF6 ), inhibitor of nuclear factor kappa-B kinase subunit alpha ( IKKα ), and nuclear factor kappa B subunit 1 ( NFκB ) caused by GABA incubation. Furthermore, incubation of hemocytes with GABA resulted in a decrease in cAMP content, an increase in intracellular Ca 2+ , and downregulation of cAMP-dependent protein kinase ( PKA ), calmodulin kinase II ( CAMK2 ), calmodulin ( CaM ), calcineurin ( CaN ), TRAF6 , IKKα , and NFκB . All these above-mentioned changes were found to be evidently relieved by blocking the metabotropic G-protein-coupled GABA B receptor. Our results suggest GABA may play an inhibitory role on phagocytosis through binding to both GABA A and GABA B receptors, and subsequently regulating corresponding downstream pathways in bivalve invertebrates.
研究领域:
免疫学
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分子生物学
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海洋生物学
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无脊椎动物生理学
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PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
·
2023
·
IF 4.3
Lingzheng Lu,Wei Huang,Yu Han,Difei Tong,Shuge Sun,Yihan Yu,Guangxu Liu,Wei Shi
Since most marine invertebrates adopted external fertilisation, their fertilisation process is particularly vulnerable to aquatic pollutants. Both antimicrobial ingredients and microplastics (MPs) are ubiquitous in aquatic environments; however, their synergistic effects on the fertilisation of marine invertebrates remain unclear. Therefore, in this study, the fertilisation toxicity of MPs and triclosan (TCS), alone and in combination, was investigated in the broadcast spawning bivalve Tegillarca granosa . Results showed that MPs and TCS significantly suppressed the fertilisation success of T . granosa . As the fertilisation success of broadcast spawning invertebrates depends on successful gamete collisions, gamete fusion, and egg activation, sperm swimming velocity, viability, gamete collision probability, ATP status, and ion-transport enzyme activities were also analysed to further ascertain the underlying toxicity mechanisms. In summary, our findings indicate that the presence of MPs may enhance the fertilisation toxicity of TCS by hampering sperm-egg collision probability, reducing gamete fusion efficiency, and restricting Ca 2+ oscillation formation.
研究领域:
海洋生物学
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环境毒理学
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水生生态学
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DOI
PubMed
高影响因子
Fishes
·
2024
·Vol. 9
·期 12
·512
·
IF 2.1
Lili Pu,Shuting Dai,Zongming Wu,Sufang Wang,Yongbo Bao
This study investigates the essential role of the heme cavity in the peroxidase and antibacterial activities of homodimeric hemoglobin (Tg-HbI) from the blood clamTegillarca granosa. After treatment with sodium dodecyl sulfate (SDS), the peroxidase and antibacterial activities of the Tg-HbI were significantly inhibited, with the degree of inhibition correlating positively with the SDS concentration. Fluorescence spectroscopy, UV-Vis spectroscopy, and molecular docking analysis further revealed that SDS interacts with key amino acid residues (e.g., His70 and His102) in the heme cavity of Tg-HbI, causing conformational changes that disrupt the internal hydrophobic interactions, thus inhibiting its function. This study confirms that the antibacterial effect of Tg-HbI is mediated through its peroxidase activity and that the heme cavity plays a critical role in maintaining this activity. These findings lay a foundation for further research on the immune defense functions of hemoglobin and provide new insights into the mechanisms of environmental adaptation inT. granosa.
研究领域:
生物化学
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免疫学
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海洋生物学
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分子生物学
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高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2018
·
IF 3.185
Wei Shi,Xiaofan Guan,Yu Han,Cheng Guo,Jiahuan Rong,Wenhao Su,Shanjie Zha,Yichen Wang,Guangxu Liu
Exposure to heavy metals such as Cadmium (Cd) may exert detrimental impacts on the immune responses of marine bivalve species. However, the immunotoxicity of Cd on blood clams remains unknown to date. Furthermore, though Cd 2+ is known to compete with calcium (Ca 2+ ) ions for their binding sites in cells and inhibit Ca 2+ influx, whether Cd 2+ weakens the immune responses of marine bivalves through inducing intracellular Ca 2+ disorders still remains unclear. Therefore, the immunotoxicity of Cd 2+ at different waterborne Ca 2+ concentrations on blood clam, Tegillarca granosa , were investigated in the present study. Results obtained demonstrated that the total number, phagocytic activity , and red granulocytes ratio of the haemocytes were all significantly reduced after 10 days exposure of individuals to 25 μg/L Cd 2+ . However, when the waterborne Ca 2+ concentrations were elevated by 10% and 20% (approximately 370 and 410 mg/L, respectively), mitigation effects on the immune responses of individuals were detected. In addition, though the expressions of genes from the Ca 2+ signaling and Ca 2+ -related apoptosis pathways were significantly altered by Cd 2+ exposure, the expression patterns of these genes were similar to that of the control when the waterborne Ca 2+ concentrations were elevated, suggesting a relieving effect of waterborne Ca 2+ on Cd 2+ induced toxicity to haemocytes. The results obtained in the present study revealed that waterborne Cd 2+ may hamper the immune responses of T. granosa through influencing Ca 2+ signaling and Ca 2+ -related apoptosis pathways, which can be partially mitigated by elevating the waterborne Ca 2+ concentrations.
研究领域:
海洋生物学
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毒理学
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免疫学
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PubMed
高影响因子
GENE
·
2022
·
IF 3.913
Zongfang Li,Min Li,Guoqiang Xiao,Shuangshuang Teng
Exposure to cadmium (Cd), a heavy metal, can cause strong and toxic side effects. Cd can enter the body of organisms in several ways, leading to various pathological reactions in the body. Tegillarca granosa is a kind of bivalve shellfish favored by people in the coastal areas of China. Bivalve shellfish can easily absorb heavy metal pollutants from water bodies while filter feeding. T. granosa is considered a hyper-accumulator of Cd, and the TgABCA3 gene is highly expressed in individuals with a high content of Cd-exposed blood clam. However, it is unclear whether TgABCA3 is involved in Cd ion transport in blood clam and the molecular mechanism for the mechanism of the Cd-induced responses for maintaining cell homeostasis. In this study, the complete cDNA of the TgABCA3 gene was analyzed to provide insights into the roles of TgABCA3 in resistance against Cd in blood clam. The complete sequence of TgABCA3 showed high identity to that of TgABCA3 from other bivalves and contained some classical motifs of ATP-binding cassette transport proteins. TgABCA3 expression in different tissues was measured using real-time quantitative polymerase chain reaction (qRT-PCR) and western blot analysis. The tissue-specific expression showed that TgABCA3 expression was highest in the gill tissue. The TgABCA3 expression in the gill tissue was silenced using the RNA interference technique. After TgABCA3 silencing, the TgABCA3 expression decreased, the Cd content increased, the oxygen consumption and ammonia excretion rates increased, and the ingestion rate decreased. These results showing that the extents of Cd accumulation and resulting toxic effects are related to expression levels and activity of TgABCA3 indicate that TgABCA3 has a protective function against Cd in the clam. This increase in Cd accumulation results in serious damage to the body, leading to the enhancement of its physiological metabolism. Therefore, the findings of the study demonstrated that TgABCA3 can participate in the transport of Cd ions in the blood clam through active transport and play a vital role in Cd detoxification.
研究领域:
海洋生物学
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分子遗传学
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环境毒理学
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PubMed
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
·
2020
·Vol. 45
·期 1
·e13517
·
IF 1.662
Gaoshang Li,Junqi Zhan,Anqi Xu,Beibei Tan,Nan Sun,Chen Wang,Ru Jia,Chao Li,Jinjie Zhang,Wenge Yang
The increased interest in achieving, solely through diet, the same effect on iron levels with supplementation, leads to numerous studies on iron absorption of iron binding proteins (IBPs). The characteristics of IBPs from Tegillarca granosa ( T. granosa ) and its iron utilization were determined to analyze their relationship. The results showed in T. granosa , Fe(ӀӀ) was main iron form in hemoglobin (TH) and that Fe(ӀӀ) and Fe(ӀӀӀ) coexisted in ferritin (TF). After in vitro digestion, TH was easier to be digested than TF, bovine hemoglobin, and bovine ferritin. In caco-2 cells model, iron bioavailability of TH also was the best, which related to TH's superior fluid properties, higher ratios of α-helix to β-sheet and amide I to amide II. These suggest TH could be used as a good source of organic iron and provide references for application of T. granosa in human nutrition. Practical applications This research investigated the iron bioavailability and structural properties of iron-binding proteins from Tegillarca granosa ( T. granosa ). Moreover, the effects of iron absorption in bovine hemoglobin and ferritin were compared with those from T. granosa . The results showed the hemoglobin in T. granosa had better iron bioavailability and it could be a good source of iron. These data could provide a basic instruction of the application of T. granosa in functional food production.
研究领域:
营养学
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蛋白质化学
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食品科学
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PubMed
高影响因子
MARINE POLLUTION BULLETIN
·
2025
·
IF 4.9
Yuyao Jiang,Yujia Yan,Yanru Guan,Jason T. Magnuson,Zijie Ding,Qingqing Ke,Aoxue Wang,Kun Qiao,Shuying Li,Wenjun Gui,Daniel Schlenk
The pervasive presence of pentachlorophenol (PCP) in aquatic-benthic ecosystems poses a threat to organisms. However, the toxicological mechanisms of PCP in benthic organisms are limited. In this study, Tegillarca granosa , a representative bivalve species, was treated with environmentally relevant concentrations of PCP (1, 10, and 100 μg/kg) and positive control for 28 days via sediment exposure to investigate bioaccumulation potential, metabolomic profiles, and histopathology. The biota-sediment bioaccumulation factor for PCP was 9.1. Given the capability of PCP to act as an uncoupler of oxidative phosphorylation, studies were performed to determine key events in the adverse outcome pathway associated with this molecular initiating event. Metabolic profiles indicated a disruption in lipid metabolism, as well as imbalances in the quantity of calcium, which was associated with the synthesis of reactive oxygen species (ROS). A reduction in adenosine-5′-triphosphate (ATP) levels were seen in clams treated with PCP and in animals treated with carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone (FCCP), which served as a positive control. When clams were co-exposed to 100 μg/kg PCP and 500 μg/kg ATP, PCP toxicity was diminished and levels of mitochondrial calcium, as well as ROS, were reduced. These results suggest that mitochondrial impairment is a key event in the toxic mechanism of PCP to T. granosa .
研究领域:
环境毒理学
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海洋生物学
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代谢组学
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生态毒理学
·
分子生物学
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DOI
PubMed
高影响因子
Frontiers in Physiology
·
2019
·
IF 3.201
Shi Wei,Han Yu,Guan Xiaofan,Rong Jiahuan,Du Xueying,Zha Shanjie,Tang Yu,Liu Guangxu
Widespread applications of cadmium (Cd) in various products have caused Cd contamination in marine ecosystems. Meanwhile, human activities in the ocean have also generated an increasing amount of noise in recent decades. Although anthropogenic noise and Cd contaminants could be present simultaneously in marine environments, the physiological responses of marine bivalve mollusks upon coexposure to anthropogenic noise and toxic metal contaminants, including Cd remain unclear. Therefore, the combined effects of anthropogenic noise and Cd on the physiological characteristics of the blood clam Tegillarca granosa were investigated in this study. The results showed that 10 days of coexposure to anthropogenic noise and Cd can enhance adverse impacts on metabolic processes, as indicated by the clearance rate, respiration rate, ammonium excretion rate, and O:N ratio of T. granosa. In addition, both the ATP content, ATP synthase activity and genes encoding important enzymes in ATP synthesis significantly declined after coexposures to anthropogenic noise and Cd, which have resulted from reduced feeding activity and respiration. Furthermore, the expressions of neurotransmitter-related genes (MAO, AChE, and mAChR3) were all significantly down-regulated after coexposure to anthropogenic noise and Cd, which suggests an enhanced neurotoxicity under coexposure. In conclusion, our study demonstrated that anthropogenic noise and Cd would have synergetic effects on the feeding activity, metabolism, and ATP synthesis of T. granosa, which may be due to the add-on of stress responses and neurotransmitter disturbances.
研究领域:
海洋生物学
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环境科学
·
毒理学
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DOI
PubMed
高影响因子
AQUATIC TOXICOLOGY
·
2023
·
IF 4.5
Yu Han,Weixia Zhang,Yu Tang,Wei Shi,Zhiquan Liu,Imane Lamine,Hangjun Zhang,Jing Liu,Guangxu Liu
Omnipresent presence of triclosan (TCS) in aqueous environment puts a potential threat to organisms. However, it's poorly understood about its immunometabolic impacts of marine invertebrates. In present study, we use a representative bivalve blood clam ( Tegillarca granosa ) as a model, investigating the effects of TCS exposure at 20 and 200 μg/L for 28 days on immunometabolism, detoxification, and cellular homeostasis to explore feasible toxicity mechanisms. Results demonstrated that the clams exposed to TCS resulting in evident immunotoxic impacts on both cellular and humoral immune responses, through shifting metabolic pathways and substances, as well as suppressing the expressions of genes from the immune– and metabolism–related pathways. In addition, significant alterations in contents (or activity) of detoxification enzymes and the expression of key detoxification genes were detected in TCS-exposed clams. Moreover, exposure to TCS also disrupted cellular homeostasis of clams through increasing MDA contents and caspase activities, and promoting activation of the apoptosis–related genes. These findings suggested that TCS might induce immunotoxic impacts by disrupting the immunometabolism, detoxification, and cellular homeostasis.
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Hanwen Zhang,Xingwen Yang,Jinyu Chen,Qihong Jiang,Shiwei Ya,Lin Chen,Xingwei Xiang
Non-alcoholic fatty liver disease (NAFLD), a prevalent chronic liver disease, is marked by excessive lipid deposition in the liver without alcohol abuse. Scapharca subcrenatum, a major Chinese farmed bivalve, yields S. subcrenatum polysaccharide (TGP), an active substance with known biological activity. Previous studies revealed TGP's significant regulatory effect on a high-fat diet (HFD)-induced NAFLD in mice. However, the precise mechanisms, particularly involving gut microbiota, remain unclear. In the current study, an antibiotic-treated mouse model was established to determine the mechanistic role of the gut microbiota in the observed anti-obesity effects of TGP. In addition, 16S rRNA genomic and metagenome-derived taxonomic analyses were performed to assess the gut microbial populations. The results showed that TGP selectively enhanced the number of the eosinophilic bacterium Lactobacillus johnsonii , which was reduced in HFD mice. Of note, the oral administration of L. johnsonii formulations to HFD mice alleviated NAFLD, and this was related to regulating lipid metabolism and the accumulation of lipids in the liver. Therefore, the current study uncovered a potential pathway for developing NAFLD treatment strategies based on the interaction between TGP and the gut microbiota.
研究领域:
药理学
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胃肠病学
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微生物学
·
代谢学
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DOI
PubMed
高影响因子
GENE
·
2022
·
IF 3.913
Defeng Zhao,Gaoyu Hu,Ran Chen,Guoqiang Xiao,Shuangshuang Teng
Cadmium (Cd) pollution threatens the cultivation of the blood clam Tegillarca granosa ( T. granosa ) in coastal regions of the East China Sea. The molecular mechanisms regulating Cd stress response and detoxification in blood clams are largely unclear. In the present study, the full-length T. granosa c-Myc (Tgc-Myc) cDNA was cloned for the first time. The 3063-bp cDNA consisted of a 129-bp 5′ untranslated region (UTR), a 1746-bp 3′ UTR, and a 1188-bp open reading frame encoding a predicted protein of 395 amino acid residues. The predicted protein had a calculated molecular weight of 44.9 kDa and an estimated isoelectric point of 6.82. The predicted protein contained an N-terminal transactivation domain and a C-terminal basic helix-loop-helix leucine zipper domain, which are conserved functional domains of c-Myc proteins. Tgc-Myc showed broad tissue distribution in blood clams, with the highest expression detected in the gill and hepatopancreas. Exposure to Cd, a major heavy metal pollutant in coastal regions of the East China Sea, induced Tgc-Myc expression in gill tissues. Tgc-Myc knockdown led to reduced expression of a variety of stress response/detoxification genes in blood clams cultivated in Cd-contaminated seawater. Tgc-Myc knockdown also led to decreased expression of IGF1R , a proto-oncogene that promotes cell proliferation. These findings indicated that Tgc-Myc regulates Cd-induced stress response and detoxification in blood clams. The upregulation of Tgc-Myc may serve as an approach to generate strains with an enhanced detoxification response and consequently a low heavy metal buildup.
研究领域:
分子生物学
·
环境毒理学
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海洋生物学
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DOI
PubMed
高影响因子
Food Science and Human Wellness
·
2023
·
IF 7
Qihong Jiang,Lin Chen,Rui Wang,Yin Chen,Shanggui Deng,Guoxin Shen,Shulai Liu,Xingwei Xiang
Type 2 diabetes mellitus (T2DM) is a complex metabolic disease threatening human health. We investigated the effects of Tegillarca granosa polysaccharide (TGP) and determined its potential mechanisms in a mouse model of T2DM established through a high-fat diet and streptozotocin. TGP (5.1 × 10 3 Da) was composed of mannose, glucosamine, rhamnose, glucuronic acid, galactosamine, glucose, galactose, xylose, and fucose. It could significantly alleviate weight loss, reduce fasting blood glucose levels, reverse dyslipidemia, reduce liver damage from oxidative stress, and improve insulin sensitivity. RT-PCR and Western blotting indicated that TGP could activate the phosphatidylinositol-3-kinase/protein kinase B signaling pathway to regulate disorders in glucolipid metabolism and improve insulin resistance. TGP increased the abundance of Allobaculum , Akkermansia , and Bifidobacterium , restored the microbiota abundance in the intestinal tracts of mice with T2DM, and promoted short-chain fatty acid production. This study provides new insights into the antidiabetic effects of TGP and highlights its potential as a natural hypoglycemic nutraceutical.
研究领域:
营养保健品
·
内分泌学
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分子生物学
·
微生物组研究
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DOI
高影响因子