RESUMO
The angiotensin II type 2 receptor (AT2R) is a well-established component of the renin-angiotensin system and is known to counteract classical activation of this system and protect against organ damage. Pharmacological activation of the AT2R has significant therapeutic benefits, including vasodilation, natriuresis, anti-inflammatory activity, and improved insulin sensitivity. However, the precise biological functions of the AT2R in maintaining homeostasis in liver tissue remain largely unexplored. In this study, we found that the AT2R facilitates liver repair and regeneration following acute injury by deactivating Hippo signaling and that interleukin-6 transcriptionally upregulates expression of the AT2R in hepatocytes through STAT3 acting as a transcription activator binding to promoter regions of the AT2R. Subsequently, elevated AT2R levels activate downstream signaling via heterotrimeric G protein Gα12/13-coupled signals to induce Yap activity, thereby contributing to repair and regeneration processes in the liver. Conversely, a deficiency in the AT2R attenuates regeneration of the liver while increasing susceptibility to acetaminophen-induced liver injury. Administration of an AT2R agonist significantly enhances the repair and regeneration capacity of injured liver tissue. Our findings suggest that the AT2R acts as an upstream regulator in the Hippo pathway and is a potential target in the treatment of liver damage.
Assuntos
Via de Sinalização Hippo , Interleucina-6 , Regeneração Hepática , Camundongos Endogâmicos C57BL , Proteínas Serina-Treonina Quinases , Receptor Tipo 2 de Angiotensina , Transdução de Sinais , Animais , Masculino , Camundongos , Acetaminofen , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Hepatócitos/metabolismo , Hepatócitos/efeitos dos fármacos , Interleucina-6/metabolismo , Fígado/metabolismo , Fígado/efeitos dos fármacos , Regeneração Hepática/efeitos dos fármacos , Regeneração Hepática/fisiologia , Camundongos Knockout , Proteínas Serina-Treonina Quinases/metabolismo , Receptor Tipo 2 de Angiotensina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Proteínas de Sinalização YAP/metabolismoRESUMO
CONTEXT: Prunella vulgaris L (Labiatae) is commonly used as a traditional medicinal herb in some Asian and Europe countries. To date, few studies have been conducted to determine the influence of [Formula: see text] - N/[Formula: see text] - N ratio on growth, physiological development, and bioactive phytochemical accumulation in hydroponically grown P. vulgaris. OBJECTIVE: The current study was conducted to evaluate the effect of five [Formula: see text] - N/[Formula: see text] - N ratios on growth, nitrogen metabolism, photosynthetic efficiency, and bioactive phytochemical production in P. vulgaris. MATERIALS AND METHODS: Hydroponically cultivated P. vulgaris were fertilized with five [Formula: see text] - N/[Formula: see text] - N ratios in a greenhouse for 85 d. Dried weight of root, stem, leaf and spica, leaf area, photosynthetic efficiency, activities of nitrate reductase (NR), glutamine synthetase (GS), and the concentrations of N, soluble protein, and free amino acids in the leaves, as well as the contents of rosmarinic acid (RA), ursolic acid (UA), and oleanolic acid (OA) in the spicas were measured. RESULTS: Both [Formula: see text] - N and [Formula: see text] - N as the sole source of nitrogen had inhibitory effects on P. vulgaris growth. P. vulgaris fertilized with the 25/75 ([Formula: see text] - N/NO3 - N) ratio had the highest leaf area, photosynthetic rate, and chlorophyll content. The 25/75 ([Formula: see text]/[Formula: see text]) ratio increased the spica biomass by 1828%, nitrate-reductase (NR) activity by 98%, and soluble protein concentration by 29.45% compared with the 100/0 ([Formula: see text]/[Formula: see text]) treatment. Additionally, 25 [Formula: see text] - N/75 NO3 - N resulted in the highest contents of RA and total flavonoids as well as relatively high contents of UA and OA; therefore, this ratio had the highest yield of RA, UA, OA, and total flavonoids in spicas. DISCUSSION AND CONCLUSION: The use of 25 [Formula: see text] - N/75 [Formula: see text] - N is recommended to improve biomass production and medicinal quality of P. vulgaris.
Assuntos
Compostos de Amônio/química , Nitratos/química , Nitrogênio/metabolismo , Prunella/fisiologia , Biomassa , Medicina Tradicional , Fotossíntese/fisiologia , Prunella/química , Prunella/crescimento & desenvolvimentoRESUMO
Label-free quantitative proteomic analysis was utilized to determine the key proteins that affect texture properties of sea cucumber body wall (SCBW) with different boiling heating treatment. 862, 363, 315, and 258 proteins were confirmed in water-soluble fractions from fresh group, 0.5 h-, 2 h- and 4 h-heat treatment group, respectively. During boiling heating treatment, proteins with an increased abundance in water-soluble fraction primarily belong to structural proteins, such as collagens, microfibril-associated proteins, glycoproteins, and muscle proteins. It was speculated that the degradation of these structural proteins caused the progressive disintegration of network skeleton of collagen fibres and FMs as well as the gelatinization, thus resulted in the decrease of hardness and shear force. Besides, the degradation of FMs was occurred layer by layer during boiling heating treatment, and the fibrilin-1 outer layer degraded first, followed by the fibrilin-2 core component.
Assuntos
Pepinos-do-Mar , Animais , Pepinos-do-Mar/química , Proteoma/metabolismo , Água/metabolismo , Proteômica , CalefaçãoRESUMO
Differences in texture and digestive properties of different parts in 80 °C-boiled abalone muscle (adductor and transition part) after different processing time were investigated. With the extension of boiling time, the shear force and hardness of adductor increased first (6 min) and then decreased (30 min and 240 min), while the two indexes of transition part dramatically decreased after boiling for 6 min and then maintained until 240 min. Meanwhile, for adductor, the degree of protein hydrolysis, protein digestibility, and peptide transport levels declined with the extension of boiling time; While for transition part, those protein digestion and transport indexes significantly decreased first (6 min and 30 min) and then increased (240 min). By contrast, the adductor contained higher myofibrillar proteins content but lower collagen content than the transition part, which contributed to the differences in texture and digestive properties of the boiled samples.
Assuntos
Digestão , Gastrópodes , Animais , Alimentos Marinhos , Músculos , DurezaRESUMO
The precise mechanism of texture changes in abalone muscles during boiling was investigated using quantitative proteomic analysis. A total 353 water-soluble proteins were identified in fresh abalone muscle. The number was decreased to 233 (6 min) and 201 (30 min), and then increased to 271 (240 min) during boiling. The undetectable protein in water-soluble fraction caused by boiling mainly belong to hemocyanins, protein kinases, dehydrogenases, phosphorylases, and transferases, while the newly identified proteins in water-soluble fraction during boiling mainly belong to collagen and myofibrillar proteins (MPs).Additionally, results also showed that boiling caused protein oxidation, denaturation, aggregation, crosslinking and degradation. Combined with the texture changes of abalone muscles during boiling, it was speculated that the oxidation, denaturation, aggregation and crosslinking of proteins led to the increase of shear force, however, the degradation of structural proteins such as MPs and collagen caused the decreases in shear force and hardness.
Assuntos
Gastrópodes , Proteômica , Animais , Colágeno/análise , Gastrópodes/química , Músculos/química , Alimentos Marinhos/análise , Água/análiseRESUMO
The effects of oxidation on protein digestion and transport in cooked abalone muscles were investigated using a combination of simulated digestion and everted-rat-gut-sac models for the first time. Boiling heat treatments caused protein oxidation in the abalone muscles, reflected by increases in the carbonyl group and disulfide bond contents, protein hydrophobicity and aggregation degree, as well as decreases in the free sulfhydryl group and amino acid contents. Protein oxidation significantly inhibited the degree of hydrolysis, digestion rate, and digestibility of the abalone muscles in the simulated digestion model. The results from the everted-rat-gut-sac model showed that amino acid and peptide transport levels from the digestion products of the cooked abalone muscles were lower than those of the uncooked samples. In contrast, the addition of antioxidants of bamboo leaves mitigated heat-treatment-induced protein oxidation, aggregation and increased hydrophobicity, and consequently improved abalone muscle protein digestibility and transport levels.
Assuntos
Antioxidantes , Gastrópodes/química , Músculos/metabolismo , Sasa/química , Alimentos Marinhos , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Digestão/efeitos dos fármacos , Masculino , Modelos Biológicos , Músculos/química , Oxirredução , Folhas de Planta/química , Ratos , Ratos Sprague-DawleyRESUMO
The objective of this study was to evaluate the change of lipids in two whelk samples during cold storage. Results showed that the peroxide value (PV) and thiobarbituric acid reactive substance (TBARS) increased while the percentage of polyunsaturated fatty acid decreased, indicating that lipid oxidation occurred. The cold storage significantly reduced the levels of triacylglycerol (TAG), polar lipid (PoL), phosphatidylcholine (PC) and phosphatidylethanolamine (PE) but increased the levels of acid value (AV), free fatty acid (FFA) and monoacylglycerol, suggesting the hydrolysis of lipids. Moreover, the results showed that the lipoxygenase, acid lipase and phospholipase contributed to the hydrolysis and oxidation of lipids in the two whelks. Additionally, partial least squares discriminant analysis showed PC was positively correlated with PE, PoL and TAG, but negatively correlated with AV, FFA, PV and TBARS, indicating there is a close relationship between hydrolysis and oxidation of lipids.
Assuntos
Fosfatidilcolinas , Alimentos Marinhos , Hidrólise , Lipase , Oxirredução , Alimentos Marinhos/análiseRESUMO
Texture deterioration occurs in adductor muscle of scallop (Argopecten irradians) (AMS) after 5 d of cold storage. Principal component analysis indicated the texture deterioration resulted in significant decrease of hardness, springiness, adhesiveness and chewiness, but significantly increased cohesiveness. Endogenous proteases degraded structural proteins, among which cysteine proteases were mainly responsible for myofibrillar proteins (MPs) degradation, while serine proteases degraded both MPs and connective tissue proteins. Pearson coefficient analysis showed that texture indicators significantly correlated with structural protein indicators in AMS. To be more specific, the hardness, springiness, adhesiveness and chewiness negatively correlated with myofibrillar fragmentation index, soluble hydroxyproline (Hyp) and soluble glycosaminoglycans, but positively correlated with solubility of MPs and water holding capacity. Meanwhile, the cohesiveness positively correlated with soluble Hyp. The Taylor diagram and Hierarchical cluster analysis confirmed that the inhibitors of cysteine and serine proteases could effectively retard textural deterioration of AMS during 5 d of cold storage.
RESUMO
Live sea cucumbers (Stichopus japonicus) were stored in a solution containing oxalic acid and tea polyphenols as natural metal ion chelators. The inhibitory effects of these chelators on the autolysis phenomenon and the underlying mechanism of action were investigated for the first time by using scanning electron microscopy, differential scanning calorimetry, low-field nuclear magnetic resonance and confocal laser scanning microscopy. External stimuli cause autolysis through the release of calcium ions (Ca2+) from cells into the extracellular connective tissue, initiating activity of the matrix metalloprotease (MMP) in the sea cucumber body wall (SCBW). MMP subsequently degrades the microfibrillar networks, that support the interconnecting collagen fibres and the interfibrillar proteoglycan bridges linking the collagen fibrils, to release the water restricted within the interspaces between collagen fibres and collagen fibrils, ultimately causing mucoid degeneration of SCBW. The natural metal ion chelators significantly inhibited the activation of MMP by chelating Ca2+, consequently effectively preventing the autolysis of SCBW.
Assuntos
Pepinos-do-Mar , Stichopus , Animais , Autólise , Quelantes , ColágenoRESUMO
The effects of endogenous proteolysis and oxidation on mechanical properties of sea cucumber (Stichopus japonicus) during thermal processing and storage and their control were investigated. The lactic acid (LA) + tea polyphenols (TP)-treated sea cucumbers showed relatively higher values in texture and rheological indicators than the blank control group after thermal processing. By contrast, the (LA + TP)-treated sea cucumbers also had lower values in water-soluble hydroxyproline, glycosaminoglycans and proteins, trichloroacetic acid-soluble peptide content, and more orderly secondary structure of proteins, indicating that the additives affected the mechanical properties of thermally processed sea cucumbers by preventing the proteolysis of proteins. All texture and rheological indicators of thermally processed sea cucumbers decreased time-dependently during chilled storage. The additives (LA + TP) significantly prevented the progressive deterioration in mechanical properties by retarding the changes in microstructure as well as phase state and distribution of water through preventing protein oxidation.