RESUMEN
Aging muscle experiences functional decline in part mediated by impaired mitochondrial ADP sensitivity. Elamipretide (ELAM) rapidly improves physiological and mitochondrial function in aging and binds directly to the mitochondrial ADP transporter ANT. We hypothesized that ELAM improves ADP sensitivity in aging leading to rescued physiological function. We measured the response to ADP stimulation in young and old muscle mitochondria with ELAM treatment, in vivo heart and muscle function, and compared protein abundance, phosphorylation, and S-glutathionylation of ADP/ATP pathway proteins. ELAM treatment increased ADP sensitivity in old muscle mitochondria by increasing uptake of ADP through the ANT and rescued muscle force and heart systolic function. Protein abundance in the ADP/ATP transport and synthesis pathway was unchanged, but ELAM treatment decreased protein s-glutathionylation incuding of ANT. Mitochondrial ADP sensitivity is rapidly modifiable. This research supports the hypothesis that ELAM improves ANT function in aging and links mitochondrial ADP sensitivity to physiological function. ELAM binds directly to ANT and ATP synthase and ELAM treatment improves ADP sensitivity, increases ATP production, and improves physiological function in old muscles. ADP (adenosine diphosphate), ATP (adenosine triphosphate), VDAC (voltage-dependent anion channel), ANT (adenine nucleotide translocator), H+ (proton), ROS (reactive oxygen species), NADH (nicotinamide adenine dinucleotide), FADH2 (flavin adenine dinucleotide), O2 (oxygen), ELAM (elamipretide), -SH (free thiol), -SSG (glutathionylated protein).
Asunto(s)
Adenosina Trifosfato , Mitocondrias , Mitocondrias/metabolismo , Adenosina Trifosfato/metabolismo , Adenosina Difosfato/farmacología , Adenosina Difosfato/metabolismo , Péptidos/farmacología , Péptidos/metabolismoRESUMEN
Aging muscle experiences functional decline in part mediated by impaired mitochondrial ADP sensitivity. Elamipretide (ELAM) rapidly improves physiological and mitochondrial function in aging and binds directly to the mitochondrial ADP transporter ANT. We hypothesized that ELAM improves ADP sensitivity in aging leading to rescued physiological function. We measured the response to ADP stimulation in young and old muscle mitochondria with ELAM treatment, in vivo heart and muscle function, and compared protein abundance, phosphorylation, and S-glutathionylation of ADP/ATP pathway proteins. ELAM treatment increased ADP sensitivity in old muscle mitochondria by increasing uptake of ADP through the ANT and rescued muscle force and heart systolic function. Protein abundance in the ADP/ATP transport and synthesis pathway was unchanged, but ELAM treatment decreased protein s-glutathionylation incuding of ANT. Mitochondrial ADP sensitivity is rapidly modifiable. This research supports the hypothesis that ELAM improves ANT function in aging and links mitochondrial ADP sensitivity to physiological function.
RESUMEN
The age-related decline in skeletal muscle mass and function is known as sarcopenia. Sarcopenia progresses based on complex processes involving protein dynamics, cell signaling, oxidative stress, and repair. We have previously found that 8-week treatment with elamipretide improves skeletal muscle function, reverses redox stress, and restores protein S-glutathionylation changes in aged female mice. This study tested whether 8-week treatment with elamipretide also affects global phosphorylation in skeletal muscle consistent with functional improvements and S-glutathionylation. Using female 6-7-month-old mice and 28-29-month-old mice, we found that phosphorylation changes did not relate to S-glutathionylation modifications, but that treatment with elamipretide did partially reverse age-related changes in protein phosphorylation in mouse skeletal muscle.
Asunto(s)
Sarcopenia , Ratones , Femenino , Animales , Sarcopenia/metabolismo , Envejecimiento/fisiología , Músculo Esquelético/metabolismo , Oligopéptidos , Proteoma/metabolismoRESUMEN
Lipids have essential biological functions in the body (e.g., providing energy storage, acting as a signaling molecule, and being a structural component of membranes); however, an excess of lipids can promote tumorigenesis, colonization, and metastatic capacity of tumor cells. To metastasize, a tumor cell goes through different stages that require lipid-related metabolic and structural adaptations. These adaptations include altering the lipid membrane composition for invading other niches and overcoming cell death mechanisms and promoting lipid catabolism and anabolism for energy and oxidative stress protective purposes. Cancer cells also harness lipid metabolism to modulate the activity of stromal and immune cells to their advantage and to resist therapy and promote relapse. All this is especially worrying given the high fat intake in Western diets. Thus, metabolic interventions aiming to reduce lipid availability to cancer cells or to exacerbate their metabolic vulnerabilities provide promising therapeutic opportunities to prevent cancer progression and treat metastasis.
Asunto(s)
Neoplasias , Humanos , Neoplasias/metabolismo , Metabolismo de los Lípidos , Transducción de Señal , Estrés Oxidativo , LípidosRESUMEN
It has been demonstrated that elamipretide (SS-31) rescues age-related functional deficits in the heart but the full set of mechanisms behind this have yet to be determined. We investigated the hypothesis that elamipretide influences post-translational modifications to heart proteins. The S-glutathionylation and phosphorylation proteomes of mouse hearts were analyzed using shotgun proteomics to assess the effects of aging on these post-translational modifications and the ability of the mitochondria-targeted drug elamipretide to reverse age-related changes. Aging led to an increase in oxidation of protein thiols demonstrated by increased S-glutathionylation of cysteine residues on proteins from Old (24 months old at the start of the study) mouse hearts compared to Young (5-6 months old). This shift in the oxidation state of the proteome was almost completely reversed by 8 weeks of treatment with elamipretide. Many of the significant changes that occurred were in proteins involved in mitochondrial or cardiac function. We also found changes in the mouse heart phosphoproteome that were associated with age, some of which were partially restored with elamipretide treatment. Parallel reaction monitoring of a subset of phosphorylation sites revealed that the unmodified peptide reporting for Myot S231 increased with age, but not its phosphorylated form and that both phosphorylated and unphosphorylated forms of the peptide covering cMyBP-C S307 increased, but that elamipretide treatment did not affect these changes. These results suggest that changes to thiol redox state and phosphorylation status are two ways in which age may affect mouse heart function, which can be restored by treatment with elamipretide.
Asunto(s)
Proteínas Musculares/química , Oligopéptidos , Procesamiento Proteico-Postraduccional , Animales , Corazón , Ratones , Mitocondrias , Oligopéptidos/farmacología , Oxidación-ReducciónRESUMEN
Leigh syndrome is a fatal neurometabolic disorder caused by defects in mitochondrial function. Mechanistic target of rapamycin (mTOR) inhibition with rapamycin attenuates disease progression in a mouse model of Leigh syndrome (Ndufs4 knock-out (KO) mouse); however, the mechanism of rescue is unknown. Here we identify protein kinase C (PKC) downregulation as a key event mediating the beneficial effects of rapamycin treatment of Ndufs4 KO mice. Assessing the impact of rapamycin on the brain proteome and phosphoproteome of Ndufs4 KO mice, we find that rapamycin restores mitochondrial protein levels, inhibits signalling through both mTOR complexes and reduces the abundance and activity of multiple PKC isoforms. Administration of PKC inhibitors increases survival, delays neurological deficits, prevents hair loss and decreases inflammation in Ndufs4 KO mice. Thus, PKC may be a viable therapeutic target for treating severe mitochondrial disease.
Asunto(s)
Enfermedades Mitocondriales/tratamiento farmacológico , Proteína Quinasa C/biosíntesis , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Sirolimus/farmacología , Sirolimus/uso terapéutico , Animales , Química Encefálica/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Complejo I de Transporte de Electrón/biosíntesis , Complejo I de Transporte de Electrón/genética , Enfermedad de Leigh/tratamiento farmacológico , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteína Quinasa C/genética , Proteoma/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/antagonistas & inhibidoresRESUMEN
Myogenesis is a complex two-phase process of proliferation and differentiation, which seems to be greatly conserved in vertebrates. For the first time in fish, we identify the changes that occur in the proteome during this process in a gilthead sea bream (Sparus aurata) myocyte primary cell culture (on days 4, 8 and 12), using 2-D gel electrophoresis and LC-MS/MS. A significant increase of myogenin expression at day 8 marked the transition from proliferation to differentiation. Of the 898 spots in the proteome analysis, the 25 protein spots overexpressed on day 4 and the 15 protein spots overexpressed on day 8 indicate the end of proliferation and the beginning of differentiation, respectively. Proliferation was characterized by enrichment of proteins involved in actin cytoskeleton remodelling and in cellular metabolic processes (transcription, ubiquitination, response to stress and glucose metabolism). During differentiation, 41 proteins were overexpressed and 51 underexpressed; many of them related to biosynthetic processes (RNA and protein synthesis and folding, and pentose pathways), terminal myotube formation and muscle contraction. The main cellular processes of both phases of muscle development in fish are similar with those observed in mammals but extended in time, allowing sequential studies of myogenesis.
Asunto(s)
Proteínas de Peces/metabolismo , Células Musculares/metabolismo , Desarrollo de Músculos/fisiología , Proteoma/metabolismo , Dorada/metabolismo , Animales , Diferenciación Celular/fisiología , Proliferación Celular/fisiología , Células Cultivadas , Modelos Animales , Factores Reguladores Miogénicos/metabolismo , Miogenina/metabolismo , Proteómica/métodos , Transducción de Señal/fisiologíaRESUMEN
Protein turnover maintains the recycling needs of the proteome, and its malfunction has been linked to aging and age-related diseases. However, not all proteins turnover equally, and the factors that contribute to accelerate or slow down turnover are mostly unknown. We measured turnover rates for 3,160 proteins in exponentially growing yeast and analyzed their dependence on physical, functional, and genetic properties. We found that functional characteristics, including protein localization, complex membership, and connectivity, have greater effect on turnover than sequence elements. We also found that protein turnover and mRNA turnover are correlated. Analysis under nutrient perturbation and osmotic stress revealed that protein turnover highly depends on cellular state and is faster when proteins are being actively used. Finally, stress-induced changes in protein and transcript abundance correlated with changes in protein turnover. This study provides a resource of protein turnover rates and principles to understand the recycling needs of the proteome under basal conditions and perturbation.
Asunto(s)
Biosíntesis de Proteínas/fisiología , Proteolisis , Proteoma/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Semivida , Presión Osmótica/fisiología , Biosíntesis de Proteínas/genética , Estabilidad Proteica , Proteínas/metabolismo , Proteómica/métodos , Estabilidad del ARN/fisiología , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/biosíntesisRESUMEN
Quantitative proteomics studies of yeast that use metabolic labeling with amino acids rely on auxotrophic mutations of one or more genes on the amino acid biosynthesis pathways. These mutations affect yeast metabolism and preclude the study of some biological processes. Overcoming this limitation, it has recently been described that proteins in a yeast prototrophic strain can also be metabolically labeled with heavy amino acids. However, the temporal profiles of label incorporation under the different phases of the prototroph's growth have not been examined. Labeling trajectories are important in the study of protein turnover and dynamics, in which label incorporation into proteins is monitored across many time points. Here we monitored protein labeling trajectories for 48 h after a pulse with heavy lysine in a yeast prototrophic strain and compared them with those of a lysine auxotrophic yeast. Labeling was successful in prototroph yeast during exponential growth phase but not in stationary phase. Furthermore, we were able to determine the half-lives of more than 1700 proteins during exponential phase of growth with high accuracy and reproducibility. We found a median half-life of 2 h in both strains, which corresponds with the cellular doubling time. Nucleolar and ribosomal proteins showed short half-lives, whereas mitochondrial proteins and other energy production enzymes presented longer half-lives. Except for some proteins involved in lysine biosynthesis, we observed a high correlation in protein half-lives between prototroph and auxotroph strains. Overall, our results demonstrate the feasibility of using prototrophs for proteomic turnover studies and provide a reliable data set of protein half-lives in exponentially growing yeast.
Asunto(s)
Proteínas de Saccharomyces cerevisiae/análisis , Saccharomyces cerevisiae/metabolismo , Células Cultivadas , Cromatografía Liquida , Proteómica , Saccharomyces cerevisiae/citología , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Espectrometría de Masas en TándemRESUMEN
All functions in animals rely on daily rhythms, and mealtime can act as a rhythm-marker of nutrients assimilation and use. The effects of meal timing and food composition on carbohydrate use and protein retention of gilthead sea bream were studied. Three groups were fed twice a day (10am and at 5pm) for two months with two alternating diets: a commercial diet (Cd) and a high-carbohydrate, low-protein diet (Ed). The Ed/Cd group received the Ed diet in the morning and the Cd diet in the afternoon, and the Cd/Ed group received these diets in the reverse order. The Cd/Cd group only received the commercial diet (control group). After 56days, two force-feeding experiments (PF1 and PF2) measured for all three groups the fate of a single meal labelled with (15)N-protein and (13)C-starch through the retention of both isotopes in the main organs and tissue reserves. In PF1 fish were fed at 10am (morning mealtime), and in PF2 at 5pm (afternoon mealtime). Fish were sampled at the next two mealtimes (PF1: 7 and 24h post-feeding, PF2: 17 and 24h post-feeding). Nutrients recovery differed according to, first, the dietary regime, and second, the last meal received (Cd or Ed). Daily lower protein intake was compensated with higher protein retention combined with more use of carbohydrates for energy. Nevertheless, carbohydrates from the morning meal were used more efficiently. So, the use of carbohydrate for energy production and protein for growth can be improved by adjusting diet composition and mealtime.
Asunto(s)
Ritmo Circadiano , Dieta , Carbohidratos de la Dieta/metabolismo , Proteínas en la Dieta/metabolismo , Marcaje Isotópico , Dorada/metabolismo , Almidón/metabolismo , Animales , Glucemia/metabolismo , Carbono/metabolismo , Isótopos de Carbono , Ingestión de Energía , Conducta Alimentaria , Hígado/metabolismo , Músculos/metabolismo , Nitrógeno/metabolismo , Isótopos de Nitrógeno , Periodo Posprandial , Dorada/sangre , Triglicéridos/sangreRESUMEN
Ideal nutritional conditions are crucial to sustainable aquaculture due to economic and environmental issues. Here we apply stable isotope analysis as an indicator of fish growth and feeding balance, to define the optimum diet for efficient growing conditions. Juveniles of gilthead sea bream were fed with six isoenergetic diets differing in protein to lipid proportion (from 41/26 to 57/20). As protein intake increased, δ¹5N and Δδ¹5N of muscle and Δδ¹5N and Δδ¹³C of its protein fraction decreased, indicating lower protein turnover and higher protein deposition in muscle. This is reflected in the inverse relationship found between Δδ¹5N and growth rate, although no differences were observed in either parameter beyond the protein/lipid proportion 47/23. Principal component analysis (PCA) also signaled 47/23 diet as the pivotal point with the highest growing efficiency, with isotopic parameters having the highest discrimination load. Thus, muscle isotope composition, especially ¹5N, can be used to evaluate nutritional status in farmed fish.
Asunto(s)
Alimentación Animal/análisis , Proteínas de Peces/análisis , Isótopos de Nitrógeno/análisis , Dorada/crecimiento & desarrollo , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Proteínas en la Dieta/metabolismo , Proteínas de Peces/metabolismo , Músculos/química , Músculos/metabolismo , Dorada/metabolismoRESUMEN
Moderate exercise enhances fish growth, although underlying physiological mechanisms are not fully known. Here we performed a proteomic and metabolic study in white (WM) and red (RM) muscle of gilthead sea bream juveniles swimming at 1.5 body lengths per second. Continuous swimming for four weeks enhanced fish growth without increasing food intake. Exercise affected muscle energy stores by decreasing lipid and glycogen contents in WM and RM, respectively. Protein synthesis capacity (RNA/protein), energy use (estimated by lipid-δ(13)C and glycogen-δ(13)C), and enzymatic aerobic capacity increased in WM, while protein turnover (expressed by δ(15)N-fractionation) did not change. RM showed no changes in any of these parameters. 2D-PAGE analysis showed that almost 15% of sarcoplasmic protein spots from WM and RM differed in response to exercise, most being over-expressed in WM and under-expressed in RM. Protein identification by MALDI-TOF/TOF-MS and LC-MS/MS revealed exercise-induced enhancement of several pathways in WM (carbohydrate catabolism, protein synthesis, muscle contraction, and detoxification) and under-expression of others in RM (energy production, muscle contraction, and homeostatic processes). The mechanism underpinning the phenotypic response to exercise sheds light on the adaptive processes of fish muscles, being the sustained-moderate swimming induced in gilthead sea bream achieved mainly by WM, thus reducing the work load of RM and improving swimming performance and food conversion efficiency.
Asunto(s)
Adaptación Fisiológica , Proteínas de Peces/metabolismo , Proteoma/metabolismo , Dorada/metabolismo , Animales , Isótopos de Carbono/metabolismo , Citrato (si)-Sintasa/genética , Citrato (si)-Sintasa/metabolismo , Complejo IV de Transporte de Electrones/genética , Complejo IV de Transporte de Electrones/metabolismo , Proteínas de Peces/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Fibras Musculares de Contracción Rápida/enzimología , Fibras Musculares de Contracción Rápida/metabolismo , Fibras Musculares de Contracción Rápida/fisiología , Fibras Musculares de Contracción Lenta/enzimología , Fibras Musculares de Contracción Lenta/metabolismo , Fibras Musculares de Contracción Lenta/fisiología , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Isótopos de Nitrógeno/metabolismo , Condicionamiento Físico Animal , Esfuerzo Físico , Análisis de Componente Principal , Biosíntesis de Proteínas , Proteoma/genética , Proteómica , Retículo Sarcoplasmático/enzimología , Retículo Sarcoplasmático/metabolismo , Dorada/genética , Dorada/crecimiento & desarrollo , Dorada/fisiología , Natación , Transcripción GenéticaRESUMEN
Here we examined the use of stable isotopes, [¹³C]starch and [¹5N]protein, as dietary tracers to study carbohydrate assimilation and distribution and protein utilisation, respectively, by rainbow trout (Oncorhynchus mykiss). The capacity of glucose uptake and use by tissues was studied, first, by varying the digestibility of carbohydrate-rich diets (30 % carbohydrate), using raw starch and gelatinised starch (GS) and, second, by observing the effects of two regimens of activity (voluntary swimming, control; sustained swimming at 1·3 body lengths/s, exercise) on the GS diet. Isotopic ratio enrichment (¹³C and ¹5N) of the various tissue components (protein, lipid and glycogen) was measured in the liver, muscles, viscera and the rest of the fish at 11 and 24 h after a forced meal. A level of 30 % of digestible carbohydrates in the food exceeded the capacity of rainbow trout to use this nutrient, causing long-lasting hyperglycaemia that raises glucose uptake by tissues, and the synthesis of glycogen and lipid in liver. Total 13C recovered 24 h post-feeding in the GS group was lower than at 11 h, indicating a proportional increase in glucose oxidation, although the deposition of lipids in white muscle (WM) increased. Prolonged hyperglycaemia was prevented by exercise, since sustained swimming enhances the use of dietary carbohydrates, mainly through conversion to lipids in liver and oxidation in muscles, especially in red muscle (RM). Higher recoveries of total 15N for exercised fish at 24 h, mainly into the protein fraction of both RM and WM, provide evidence that sustained swimming improves protein deposition, resulting in an enhancement of the protein-sparing effect.
Asunto(s)
Conducta Animal , Dieta/veterinaria , Proteínas de Peces/metabolismo , Oncorhynchus mykiss/metabolismo , Almidón/metabolismo , Natación , Animales , Metabolismo de los Hidratos de Carbono , Carbohidratos/química , Isótopos de Carbono , Dieta/efectos adversos , Digestión , Proteínas de Peces/biosíntesis , Geles , Hiperglucemia/etiología , Hiperglucemia/prevención & control , Hiperglucemia/veterinaria , Metabolismo de los Lípidos , Hígado/metabolismo , Fibras Musculares de Contracción Rápida/metabolismo , Fibras Musculares de Contracción Lenta/metabolismo , Isótopos de Nitrógeno , Oncorhynchus mykiss/sangre , Oncorhynchus mykiss/crecimiento & desarrollo , Almidón/administración & dosificación , Almidón/efectos adversos , Almidón/química , Triticum/metabolismo , Vísceras/metabolismoRESUMEN
There are few traceability systems other than genetic markers capable of distinguishing between sea products of different origin and quality. Here, we address the potential of stable isotopes combined with metabolic and growth parameters as a discriminatory tool for the selection of fish seeds with high growth capacity. For this purpose, sea bream fingerlings produced in three hatcheries (Spanish Mediterranean coast, MC; Cantabrian coast, CC; and South-Iberian Atlantic coast, AC) were subjected to isotopic analysis (δ15N and δ13C), and indices of growth (RNA and DNA) and energy metabolism [cytochrome-c-oxidase (COX) and citrate synthase (CS) activities] were calculated. These analyses were performed prior to and after a "homogenization" period of 35 days under identical rearing conditions. After this period, fingerlings were discriminated between hatcheries, with isotopic measures (especially δ15N), metabolic parameters (COX and CS), and proximal composition (fat content) in muscle providing the highest discriminatory capacity. Therefore, particular rearing conditions and/or genetic divergence between hatcheries, affecting the growth capacity of fingerlings, are defined mainly by the isotopic imprint. Moreover, the muscle isotopic signature is a more suitable indicator than whole fish for discrimination purposes.
Asunto(s)
Explotaciones Pesqueras , Isótopos/análisis , Dorada/clasificación , Animales , Isótopos de Carbono/análisis , Metabolismo Energético , Músculos/metabolismo , Isótopos de Nitrógeno/análisis , Dorada/crecimiento & desarrollo , Dorada/metabolismoRESUMEN
Two groups of juvenile gilthead sea bream were kept on two different swimming regimes (Exercise, E: 1.5 body length s(-1) or Control, C: voluntary activity) for 1 month. All fish were first adapted to an experimental diet low in protein and rich in digestible carbohydrates (37.2% protein, 40.4% carbohydrates, 12.5% lipid). The cellularity and capillarisation of white muscle from two selected areas (cranial (Cr), below the dorsal fin, and caudal (Ca), behind the anal fin) were compared. The body weight and specific growth rate (SGR) of group E rose significantly without an increment in feed intake, pointing to higher nutrient-use efficiency. The white muscle fibre cross-sectional area and the perimeter of cranial samples increased after sustained activity, evidencing that sustained exercise enhances hypertrophic muscle development. However, we cannot conclude or rule out the possibility of fibre recruitment because the experimental period was too short. In the control group, capillarisation, which is extremely low in gilthead sea bream white muscle, showed a significantly higher number of fibres with no surrounding capillaries (F0) in the cranial area than in the caudal area, unlike the exercise group. Sustained swimming improved muscle machinery even in tissue normally associated with short bouts of very rapid anaerobic activity. So, through its effect on the use of tissue reserves and nutrients, exercise contributes to improvements in fish growth what can contribute to reducing nitrogen losses.
Asunto(s)
Dieta , Músculo Esquelético/crecimiento & desarrollo , Esfuerzo Físico/fisiología , Dorada/crecimiento & desarrollo , Natación/fisiología , Animales , Fenómenos Biomecánicos , Peso Corporal/fisiología , Capilares/fisiología , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/citología , Análisis de RegresiónRESUMEN
Gilthead sea bream exposed to the cold show multiple physiological alterations, particularly in liver. A typical cold-stress response was reproduced in gilthead sea bream acclimated to 20 degrees C (Warm group) when the water temperature was lowered to 8 degrees C (Cold group). After 10 days, thiobarbituric acid reactive substances in the liver had increased by 50%, and nitric oxide had increased twofold. This indicates that lipid peroxidation and oxidative stress had occurred. Protein profiles of liver from fish in warm and cold environments were obtained by 2-DE. Quantification of differential expression by matching spots showed that a total of 57 proteins were altered significantly. Many proteins were downregulated following cold exposure, including actin, the most abundant protein in the proteome; enzymes of amino acid metabolism; and enzymes with antioxidant capacity, such as betaine-homocysteine-methyl transferase, glutathione-S-transferase and catalase. Some proteins associated with protective action were upregulated at low temperatures, including peroxiredoxin, thioredoxin and lysozyme; as well as enzymes such as aldehyde dehydrogenase and adenosin-methionine synthetase. However, the upregulation of proteases, proteasome activator protein and trypsinogen-like protein indicated an increase in proteolysis. Increases in elongation factor-1alpha, the GAPDH oxidative form, tubulin and Raf-kinase inhibitor protein indicated oxidative stress and the induction of apoptosis. These data indicate that cold exposure induced oxidative damage in hepatocytes.
Asunto(s)
Frío , Hígado/metabolismo , Estrés Oxidativo , Proteoma/metabolismo , Dorada/metabolismo , Animales , Regulación hacia Abajo , Proteínas de Peces/metabolismo , Perfilación de la Expresión Génica , Oxidantes/metabolismo , Solubilidad , Estrés Fisiológico , Regulación hacia ArribaRESUMEN
OBJECTIVE: To assess the diagnostic validity, degree of patient satisfaction, and economic cost of home sleep monitoring compared to conventional polysomnography. PATIENTS AND METHODS: Consecutive patients with symptoms indicative of sleep apnea-hypopnea syndrome (SAHS) were included. We analyzed the diagnostic yield of home sleep monitoring using the apnea-hypopnea index (AHI), number of desaturations of at least 3%, and the percentage time with arterial oxygen saturation below 90%. The degree of patient satisfaction, measured on a visual analogue scale, and the cost of home monitoring were compared with conventional polysomnography. RESULTS: The study included 52 patients (42 men and 10 women) with a mean (SD) age of 51.8 (9) years and a body mass index of 32 (5) kg/m2. Polysomnography and home monitoring revealed an AHI of 33.6 (20) and 31 (19), respectively (r=0.971; intraclass correlation coefficient = 0.963; P< .001). The number of desaturations of at least 3% and the percentage time with arterial oxygen saturation below 90% showed significant correlation and concordance (P< .05). For an AHI cutoff of 10 recorded with polysomnography, home monitoring had a sensitivity of 89% and a specificity of 80%, with an area under the receiver operator characteristic curve of 0.804. For severe SAHS (AHI> or =30), the sensitivity and specificity of home monitoring was 100% (that is, the area under the receiver operating characteristic curve was 1). For home monitoring, the cost per diagnostic test was 101.34 euro less than that of polysomnography, and the patient satisfaction was significantly greater (P< .0001). CONCLUSIONS: Home sleep monitoring is a valid and cost-effective diagnostic test; patients with symptoms of SAHS are more satisfied with this technique than conventional polysomnography.
Asunto(s)
Servicios de Atención de Salud a Domicilio/economía , Satisfacción del Paciente , Polisomnografía/economía , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/economía , Análisis Costo-Beneficio , Femenino , Humanos , Masculino , Persona de Mediana Edad , EspañaRESUMEN
Objetivo: Comparar la validez diagnóstica, el grado de satisfacción del paciente y el coste económico de la poligrafía domiciliaria respecto a la polisomnografía convencional. Pacientes y métodos: Se seleccionó consecutivamente a pacientes con síntomas indicativos de síndrome de apneas-hipopneas durante el sueño (SAHS). Analizamos la rentabilidad de la poligrafía domiciliaria mediante el índice apneas-hipopneas (IAH), el índice de desaturación igual o mayor del 3% y el porcentaje de tiempo con una saturación arterial de oxígeno menor del 90%. Se compararon el grado de satisfacción del paciente, evaluada con una escala visual, y el coste de la poligrafía respecto a la polisomnografía. Resultados: Se incluyó en el estudio a 52 pacientes (42 varones y 10 mujeres) con una edad media ± desviación estándar de 51,8 ± 9 años e índice de masa corporal de 32 ± 5 kg/m2. La polisomnografía y la poligrafía obtuvieron un IAH de 33,6 ± 20 y de 31 ± 19, respectivamente (r = 0,971; coeficiente de correlación intraclase = 0,963; p < 0,001). Los valores del índice de desaturación igual o mayor del 3% y el porcentaje de tiempo con una saturación arterial de oxígeno menor del 90% mostraron una correlación y concordancia significativas (p < 0,05). Para un IAH obtenido en la polisomnografía de 10, la poligrafía mostró una sensibilidad del 89% y una especificidad del 80%, con un área bajo la curva de eficacia diagnóstica de 0,804; en el SAHS grave (IAH ≥ 30) la sensibilidad y especificidad de la poligrafía fue del 100% (área bajo la curva de eficacia diagnóstica = 1). En la poligrafía, el coste por prueba diagnóstica fue 101,34 menor que en la polisomnografía, y el grado de satisfacción del paciente, significativamente mayor (p < 0,0001). Conclusiones: La poligrafía domiciliaria es una técnica diagnóstica válida y coste-eficiente, que aporta mayor grado de satisfacción que la polisomnografía convencional al paciente con síntomas de SAHS
Objective: To assess the diagnostic validity, degree of patient satisfaction, and economic cost of home sleep monitoring compared to conventional polysomnography. Patients and methods: Consecutive patients with symptoms indicative of sleep apnea-hypopnea syndrome (SAHS) were included. We analyzed the diagnostic yield of home sleep monitoring using the apneahypopnea index (AHI), number of desaturations of at least 3%, and the percentage time with arterial oxygen saturation below 90%. The degree of patient satisfaction, measured on a visual analogue scale, and the cost of home monitoring were compared with conventional polysomnography. Results: The study included 52 patients (42 men and 10 women) with a mean (SD) age of 51.8 (9) years and a body mass index of 32 (5) kg/m2. Polysomnography and home monitoring revealed an AHI of 33.6 (20) and 31 (19), respectively (r=0.971; intraclass correlation coefficient = 0.963; P<.001). The number of desaturations of at least 3% and the percentage time with arterial oxygen saturation below 90% showed significant correlation and concordance (P<.05). For an AHI cutoff of 10 recorded with polysomnography, home monitoring had a sensitivity of 89% and a specificity of 80%, with an area under the receiver operator characteristic curve of 0.804. For severe SAHS (AHI≥30), the sensitivity and specificity of home monitoring was 100% (that is, the area under the receiver operating characteristic curve was 1). For home monitoring, the cost per diagnostic test was E101.34 less than that of polysomnography, and the patient satisfaction was significantly greater (P<.0001). Conclusions: Home sleep monitoring is a valid and cost-effective diagnostic test; patients with symptoms of SAHS are more satisfied with this technique than conventional polysomnography