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1.
Amino Acids ; 54(2): 169-180, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34837556

RESUMEN

The human Dietary Approaches to Stop Hypertension-Sodium Trial has shown that ß-aminoisobutyric acid (BAIBA) may prevent the development of salt-sensitive hypertension (SSHT). However, the specific antihypertensive mechanism remains unclear in the renal tissues of salt-sensitive (SS) rats. In this study, BAIBA (100 mg/kg/day) significantly attenuated SSHT via increased nitric oxide (NO) content in the renal medulla, and it induced a significant increase in NO synthesis substrates (L-arginine and malic acid) in the renal medulla. BAIBA enhanced the activity levels of total NO synthase (NOS), inducible NOS, and constitutive NOS. BAIBA resulted in increased fumarase activity and decreased fumaric acid content in the renal medulla. The high-salt diet (HSD) decreased fumarase expression in the renal cortex, and BAIBA increased fumarase expression in the renal medulla and renal cortex. Furthermore, in the renal medulla, BAIBA increased the levels of ATP, ADP, AMP, and ADP/ATP ratio, thus further activating AMPK phosphorylation. BAIBA prevented the decrease in renal medullary antioxidative defenses induced by the HSD. In conclusion, BAIBA's antihypertensive effect was underlined by the phosphorylation of AMPK, the prevention of fumarase's activity reduction caused by the HSD, and the enhancement of NO content, which in concert attenuated SSHT in SS rats.


Asunto(s)
Fumarato Hidratasa , Hipertensión , Ácidos Aminoisobutíricos , Animales , Presión Sanguínea , Suplementos Dietéticos , Fumarato Hidratasa/genética , Fumarato Hidratasa/metabolismo , Hipertensión/tratamiento farmacológico , Hipertensión/prevención & control , Ratas , Ratas Endogámicas Dahl
2.
J Sci Food Agric ; 102(7): 2710-2722, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34708426

RESUMEN

BACKGROUND: Excessive dietary salt intake is related to an increased risk of hypertension. Dietary functional foods probably could help to improve salt-induced hypertension. In this study, Dahl salt-sensitive (DSS) rats were used to investigate their metabolic differences from those of salt-resistant SS.13BN rats and determine whether dietary protein-rich almonds could ameliorate salt-induced elevation of blood pressure in DSS rats. RESULTS: After high-salt intake, the systolic blood pressure and mean arterial pressure of the DSS rats increased dramatically. Metabolomics analysis indicated abnormal amino acid metabolism in their kidneys. Their renal nitric oxide (NO) content and nitric oxide synthase activity decreased significantly after high-salt diet. Oxidative stress also occurred in DSS rats. After the DSS rats received almond supplementation, the levels of various amino acids in their kidney increased, and renal arginine and NO contents were upregulated. Their renal hydrogen peroxide and malonaldehyde levels decreased, whereas renal catalase, superoxide dismutase and glutathione peroxidase activities and glutathione levels increased. CONCLUSION: The renal abnormal amino acid metabolism of DSS rats contributed to the impaired NO production in response to high-salt intake. Together with salt-induced oxidative stress, high-salt diet intake ultimately led to an increase in the blood pressure of DSS rats. Protein-rich almond supplementation might prevent the development of salt-induced hypertension by restoring arginine and NO regeneration and alleviating salt-induced oxidative stress. © 2021 Society of Chemical Industry.


Asunto(s)
Hipertensión , Prunus dulcis , Animales , Arginina , Presión Sanguínea , Hipertensión/inducido químicamente , Hipertensión/metabolismo , Riñón/metabolismo , Óxido Nítrico/farmacología , Ratas , Ratas Endogámicas Dahl , Cloruro de Sodio Dietético/efectos adversos
3.
Biochem Biophys Res Commun ; 553: 1-8, 2021 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-33752091

RESUMEN

BACKGROUND AND AIMS: Hypercholesterolemia is characterized by the elevation of plasma total cholesterol level, especially low-density lipoprotein (LDL) cholesterol. This disease is usually caused by a mutation in genes such as LDL receptor, apolipoprotein B, or proprotein convertase subtilisin/kexin type 9. However, a considerable number of patients with hypercholesterolemia do not have any mutation in these candidate genes. In this study, we examined the difference in the metabolic level between patients with hypercholesterolemia and healthy subjects, and screened the potential biomarkers for this disease. METHODS: Analysis of plasma metabolomics in hypercholesterolemia patients and healthy controls was performed by gas chromatography-mass spectrometry and metabolic correlation networks were constructed using Gephi-0.9.2. RESULTS: First, metabolic profile analysis confirmed the distinct metabolic footprints between the patients and the healthy ones. The potential biomarkers screened by orthogonal partial least-squares discrimination analysis included l-lactic acid, cholesterol, phosphoric acid, d-glucose, urea, and d-allose (Variable importance in the projection > 1). Second, arginine and methionine metabolism were significantly perturbed in hypercholesterolemia patients. Finally, we identified that l-lactic acid, l-lysine, l-glutamine, and l-cysteine had high scores of centrality parameters in the metabolic correlation network. CONCLUSION: Plasma l-lactic acid could be used as a sensitive biomarker for hypercholesterolemia. In addition, arginine biosynthesis and cysteine and methionine metabolism were profoundly altered in patients with hypercholesterolemia.


Asunto(s)
Biomarcadores/sangre , Biomarcadores/metabolismo , Hipercolesterolemia/sangre , Hipercolesterolemia/metabolismo , Metabolómica , Adolescente , Adulto , Arginina/metabolismo , Estudios de Casos y Controles , Colesterol/metabolismo , Cisteína/metabolismo , Femenino , Cromatografía de Gases y Espectrometría de Masas , Glucosa/metabolismo , Glutamina/metabolismo , Humanos , Ácido Láctico/sangre , Ácido Láctico/metabolismo , Lisina/metabolismo , Masculino , Metionina/metabolismo , Persona de Mediana Edad , Ácidos Fosfóricos/metabolismo , Urea/metabolismo , Adulto Joven
4.
J Huazhong Univ Sci Technolog Med Sci ; 35(2): 316-318, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25877371

RESUMEN

This study was aimed to identify the mutation of the whole coding region of shock transcription factor 4 (HSF4) gene in a Chinese family with autosomal dominant congenital cataract (ADCC). All exons of HSF4 were amplified by PCR. Sequence analysis of PCR products was performed. Restriction fragment length polymorphism (RFLP) analysis was conducted to confirm the pathogenic mutation. The results showed that a C to T substitution occurred at nucleotide 331 in patients of this family, leading to the replacement of the amino acid arginine-111 with cysteine in exon 3. RFLP analysis showed that the amino acid change was co-segregated with all affected individuals. It was concluded that the new mutation of c.331C>T in HSF4 DNA may be responsible for the autosomal dominant congenital cataract in this family.


Asunto(s)
Catarata/congénito , Proteínas de Unión al ADN/genética , Genes Dominantes , Mutación , Factores de Transcripción/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Catarata/genética , China , Cartilla de ADN , Proteínas de Unión al ADN/química , Femenino , Factores de Transcripción del Choque Térmico , Humanos , Masculino , Datos de Secuencia Molecular , Linaje , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Homología de Secuencia de Aminoácido , Factores de Transcripción/química
5.
Neurosci Bull ; 39(1): 125-137, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35821337

RESUMEN

Accurate self-motion perception, which is critical for organisms to survive, is a process involving multiple sensory cues. The two most powerful cues are visual (optic flow) and vestibular (inertial motion). Psychophysical studies have indicated that humans and nonhuman primates integrate the two cues to improve the estimation of self-motion direction, often in a statistically Bayesian-optimal way. In the last decade, single-unit recordings in awake, behaving animals have provided valuable neurophysiological data with a high spatial and temporal resolution, giving insight into possible neural mechanisms underlying multisensory self-motion perception. Here, we review these findings, along with new evidence from the most recent studies focusing on the temporal dynamics of signals in different modalities. We show that, in light of new data, conventional thoughts about the cortical mechanisms underlying visuo-vestibular integration for linear self-motion are challenged. We propose that different temporal component signals may mediate different functions, a possibility that requires future studies.


Asunto(s)
Percepción de Movimiento , Flujo Optico , Vestíbulo del Laberinto , Animales , Humanos , Percepción de Movimiento/fisiología , Teorema de Bayes , Señales (Psicología) , Vestíbulo del Laberinto/fisiología , Estimulación Luminosa , Percepción Visual/fisiología
6.
Food Funct ; 13(2): 891-903, 2022 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-34994761

RESUMEN

A high-salt (HS) diet leads to metabolic disorders in Dahl salt-sensitive (SS) rats, and promotes the development of hypertension. According to the changes in the metabolites of SS rats, a set of combined dietary supplements containing amino acids and organic acids (AO) were designed. The purpose of the present study was to evaluate the effect of AO supplementation on the blood pressure of SS rats after the HS diet and clarify the mechanism of AO by metabolomics and biochemical analyses. The results showed that AO supplementation avoided the elevation of blood pressure induced by the HS diet in SS rats, increased the renal antioxidant enzyme activities (catalase, superoxide dismutase, glutathione reductase, and glutathione S-transferase), reduced the H2O2 and MDA levels, and restored the normal antioxidant status of the serum and kidneys. AO also reversed the decrease in the nitric oxide (NO) levels and NO synthase activity induced by the HS feed, which involved the L-arginine/NO pathway. Metabolomics analysis showed that AO administration increased the levels of amino acids such as cysteine, glycine, hypotaurine, and lysine in the renal medulla and the levels of leucine, isoleucine, and serine in the renal cortex. Of note, lysine, hypotaurine and glycine had higher metabolic centrality in the metabolic correlation network of the renal medulla after AO administration. In conclusion, AO intervention could prevent HS diet-induced hypertension in SS rats by restoring the metabolic homeostasis of the kidneys. Hence, AO has the potential to become a functional food additive to improve salt-sensitive hypertension.


Asunto(s)
Aminoácidos/farmacología , Presión Sanguínea/efectos de los fármacos , Hipertensión/inducido químicamente , Cloruro de Sodio Dietético/administración & dosificación , Aminoácidos/química , Animales , Suplementos Dietéticos , Glutatión/metabolismo , Hipertensión/prevención & control , Corteza Renal/efectos de los fármacos , Corteza Renal/metabolismo , Médula Renal/efectos de los fármacos , Médula Renal/metabolismo , Masculino , Ratas , Ratas Endogámicas Dahl , Cloruro de Sodio Dietético/efectos adversos
7.
Cell Rep ; 37(7): 109999, 2021 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-34788608

RESUMEN

Precise heading perception requires integration of optic flow and vestibular cues, yet the two cues often carry distinct temporal dynamics that may confound cue integration benefit. Here, we varied temporal offset between the two sensory inputs while macaques discriminated headings around straight ahead. We find the best heading performance does not occur under natural condition of synchronous inputs with zero offset but rather when visual stimuli are artificially adjusted to lead vestibular by a few hundreds of milliseconds. This amount exactly matches the lag between the vestibular acceleration and visual speed signals as measured from single-unit-activity in frontal and posterior parietal cortices. Manually aligning cues in these areas best facilitates integration with some nonlinear gain modulation effects. These findings are consistent with predictions from a model by which the brain integrates optic flow speed with a faster vestibular acceleration signal for sensing instantaneous heading direction during self-motion in the environment.


Asunto(s)
Percepción de Movimiento/fisiología , Flujo Optico/fisiología , Equilibrio Postural/fisiología , Animales , Encéfalo/fisiología , Señales (Psicología) , Oído Interno/fisiología , Macaca mulatta , Masculino , Lóbulo Parietal/fisiología , Estimulación Luminosa , Vestíbulo del Laberinto/fisiología , Percepción Visual/fisiología
8.
Biochimie ; 181: 154-161, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33347925

RESUMEN

High salt diet (HSD, 8% NaCl) contributes to salt-sensitive hypertension, this study aimed to determine the effect of HSD on salt-sensitive hypertension by combining proteomic with metabolomics methods. Salt-sensitive rats were fed on HSD and normal salt diet (NSD, 0.4% NaCl) for two weeks before further analysis. Proteomic analysis showed the differential expression proteins (DEPs) were primarily mapped in the tricarboxylic acid (TCA)-cycle, glycolysis/gluconeogenesis, and other pathways associated with multiple amino acids. HSD decreased the medullary activities and protein expression level of two key enzymes of TCA-cycle, MDH and NADP+-IDH. Metabolomics showed three serous TCA-cycle-associated compounds, including decreased malic acid, decreased citric acid, and increased fumaric acid were differentially detected, which resulted in a decrease in NO content and an increase in H2O2 content in serum. The content of GSH, GSH/GSSG ratio, and synthesis substrates of GSH-cysteine and glycine, were significantly decreased by HSD, thus attenuated the antioxidant system in the renal medulla. HSD enhanced the medullary pentose phosphate pathway, which finally increased the concentration of NADPH and NADP+, NADPH/NADP+, and the activity of NADPH oxidase in the renal medulla. Additionally, HSD enhanced the glycolysis pathway in the renal medulla. In summary, HSD significantly weakened the TCA cycle, and attenuated the antioxidant system in the renal medulla, which finally contributed to salt-sensitive hypertension.


Asunto(s)
Antioxidantes/metabolismo , Ciclo del Ácido Cítrico/efectos de los fármacos , Hipertensión , Médula Renal/metabolismo , Cloruro de Sodio Dietético/efectos adversos , Animales , Hipertensión/inducido químicamente , Hipertensión/metabolismo , Hipertensión/patología , Médula Renal/patología , Masculino , Vía de Pentosa Fosfato/efectos de los fármacos , Ratas , Ratas Endogámicas Dahl , Cloruro de Sodio Dietético/farmacología
9.
Life Sci ; 270: 119134, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33513395

RESUMEN

AIMS: Salt-sensitive hypertension is a risk factor for cardiovascular disease. Previous studies have shown that insufficient arginine in the kidney caused by metabolic imbalance is an important factor in salt-sensitive hypertension. Whether the high nitrogen content of histidine can affect the balance of nitrogen metabolism in Dahl salt-sensitive (SS) rats. This article aimed to study the effects of oral histidine on salt-sensitive hypertension, kidney damage and metabolic patterns of high-salt diet in SS rats. MAIN METHODS: Adult rats were divided into four groups, and blood pressure was measured using a non-invasive tail-cuff system. Gas chromatography-mass spectrometry analyzed metabolites in serum and kidney tissues. KEY FINDINGS: High-salt diet significantly increased the blood pressure of rats and aggravated kidney damage. Of note, histidine can attenuate salt-sensitive hypertension and kidney damage by improving metabolic pattern, reducing Reactive Oxygen Species (ROS) and increasing nitric oxide levels in SS rats. SIGNIFICANCE: These results suggest that histidine could be a potential adjuvant to prevent and control salt-sensitive hypertension.


Asunto(s)
Histidina/farmacología , Hipertensión/tratamiento farmacológico , Administración Oral , Animales , Presión Sanguínea/efectos de los fármacos , Enfermedades Cardiovasculares/metabolismo , Dieta , Histidina/metabolismo , Hipertensión/metabolismo , Hipertensión/fisiopatología , Riñón/metabolismo , Enfermedades Renales/metabolismo , Masculino , Óxido Nítrico/metabolismo , Ratas , Ratas Endogámicas Dahl , Especies Reactivas de Oxígeno/metabolismo , Cloruro de Sodio Dietético/efectos adversos
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