RESUMEN
Women live approximately one-third of their lives in postmenopause. Among postmenopausal women, type 2 diabetes mellitus (DM2) is one of the most prevalent chronic diseases. These conditions promote alterations in the oxidative, metabolic, and immune-inflammatory profiles marked by higher extracellular 72 kDa-heat shock protein (eHSP72). Here, we investigated whether the time of menopause is associated with oxidative cellular stress marker levels in postmenopausal women with DM2. Sixty-four women were recruited (56.7 ± 12.6 years old) in the pre- (n = 22) and postmenopause (n = 42) period, with (n = 19) or without DM2 (n = 45), and a fasting blood collection was made for the evaluation of metabolic, oxidative, and inflammatory markers. We found that menopause and DM2 influenced metabolic and oxidative parameters and presented synergistic effects on the plasma lipoperoxidation levels. Also, postmenopausal women had the highest eHSP72 concentration levels associated with the years in postmenopause. We conclude that the time of menopause impacts the markers of cellular stress and increases the risk of oxidative stress, mainly when it is associated with DM2.
Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Proteínas del Choque Térmico HSP72/sangre , Estrés Oxidativo , Posmenopausia/sangre , Adulto , Anciano , Brasil , Femenino , Humanos , Persona de Mediana EdadRESUMEN
Previous studies reported that extracellular HSP72 (eHSP72) correlates with poor prognosis, markers of vascular dysfunction, and the severity of cardiovascular diseases, associated with a systemic oxidative and inflammatory profile. On the other hand, eHSP72 may represent immune-regulatory signaling that is related to exercise benefits, but the association between physical activity levels and eHSP72 levels is not established. Thus, since regular physical activity may avoid oxidative stress and inflammation, we investigate whether detectable levels of eHSP72 in plasma are associated with physical activity and antioxidant enzyme activity levels in hypertensive subjects. Physical activity levels of hypertensive subjects (n = 140) were measured by tri-axial movement sensor pedometer for 24 h during 5 consecutive days. One day after, blood was collected into heparinized tubes for oxidative stress analyses (catalase-CAT and superoxide dismutase-SOD activities and malondialdehyde levels) or in disodium EDTA tubes for eHSP72 assays. Thus, hypertensive subjects were classified as physically inactive (< 10,000 footsteps/day) or active (> than 10,000 footsteps/day) and according detectable or not detectable eHSP72 levels in plasma, performing the inactive/eHSP72-, active/eHSP72-, inactive/eHSP72+, and active/eHSP72+ groups. We found that detectable levels of eHSP72 in plasma were associated with physical activity levels and low oxidative stress profile (Higher CAT and SOD activities and low malondialdehyde levels). eHSP72 levels can be used as a biomarker of the amount of physical activity necessary to improve antioxidant defense and thus cardiovascular health in hypertensive subjects.
Asunto(s)
Biomarcadores/sangre , Ejercicio Físico , Proteínas del Choque Térmico HSP72/sangre , Hipertensión/metabolismo , Estrés Oxidativo , Anciano , Brasil/epidemiología , Catalasa/metabolismo , Femenino , Humanos , Inflamación/metabolismo , Masculino , Malondialdehído/metabolismo , Persona de Mediana Edad , Superóxido Dismutasa/metabolismoRESUMEN
INTRODUCTION: Our previous studies have shown that periapical lesions (PLs) in rats cause systemic disorders such as increased tumor necrosis factor-α plasma levels, insulin resistance, and impairment in insulin signal transduction in muscle tissue. However, the mechanisms involved in these alterations are not fully understood. Under chronic inflammatory conditions such as obesity, it has been shown that the skeletal muscle is affected by inflammation, and the number of resident macrophages that are associated with impairments of insulin action and sensitivity is increased. This study aimed to investigate the presence of macrophages, activation of inflammatory pathways in muscle tissue, glycemia, and insulinemia of rats with PLs. METHODS: Sixty Wistar rats were distributed into a control group; a group with 1 PL (1PL), which was induced in the right maxillary first molar; and a group with 4 PLs (4PL), which were induced in the right upper and lower first and second molars. We quantified macrophage content by immunohistochemistry for the F4/80 protein. We evaluated Jun N-terminal kinase and IKKα/ß phosphorylation status in the muscle tissue by Western blotting. Serum levels of lipopolysaccharide (LPS) and HSP70 and plasma levels of glucose and insulin were assessed by using commercial kits. RESULTS: The 1PL and 4PL groups showed increase in macrophage content, IKKα/ß, and Jun N-terminal kinase phosphorylation status, serum LPS and HSP70 levels, and insulin resistance and no changes in glycemia and insulinemia compared with the control group. There was no difference in these parameters between the 1PL and 4PL groups. CONCLUSIONS: PLs promoted an increase in macrophage infiltration, activation of inflammatory pathways in muscle tissue, and serum concentrations of HSP70 and LPS in rats. The present study improves the knowledge on the impact of oral inflammations on the development of systemic alteration, which can induce insulin resistance.
Asunto(s)
Inflamación/fisiopatología , Activación de Macrófagos/fisiología , Músculo Esquelético/metabolismo , Enfermedades Periapicales/fisiopatología , Animales , Glucemia/análisis , Proteínas del Choque Térmico HSP72/sangre , Quinasa I-kappa B/metabolismo , Insulina/sangre , Resistencia a la Insulina , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Lipopolisacáridos/sangre , Masculino , Músculo Esquelético/patología , Enfermedades Periapicales/metabolismo , Enfermedades Periapicales/patología , Ratas , Ratas Wistar , Transducción de Señal/fisiologíaRESUMEN
The inducible expression of the 70-kDa heat shock proteins (HSP70) is associated with homeostatically stressful situations. Stresses involving sympathetic nervous system (SNS) activation, including α1-adrenergic agonists and physical exercise, are capable of inducing HSP70 expression and release of the HSP70 inducible form, HSP72. However, whether hypoglycaemia is capable of influencing HSP70 status under a stressful situation such as insulin-induced hypoglycaemia (IIH), which also involves SNS activation, is unsettled. Hence, we decided to investigate whether the predominant signal for HSP70 expression and delivery into the blood comes from either low glucose, high insulin, or both during short-term IIH (STIIH) and long-term IIH (LTIIH). Our data indicated that low glucose level (up to 1.56 ± 0.14 mM), but not insulin, is the triggering factor responsible for a dramatic rise in HSP72 plasma concentrations (from 0.15 ± 0.01 in fed state to 0.77 ± 0.13 ng/mL during hypoglycaemic episodes). This was observed in parallel with up to 7-fold increases in interleukin-6 (IL-6) but not interleukin-10 (IL-10) or tumour necrosis factor-α (TNF-α) at STIIH. Together, the observations may suggest that HSP72 is released under hypoglycaemic conditions as a part of the homeostatic stress response, whereas at long-term, both hypoglycaemia and insulin may influence HSP72 expression in the liver, but not in kidneys. Secreted extracellular HSP72 (eHSP72) may be purely a danger signal to all the tissues of the body for the enhancement of immune and metabolic surveillance state or actively participates in glycaemic control under stressful situations.
Asunto(s)
Proteínas del Choque Térmico HSP72/sangre , Hipoglucemia/sangre , Hipoglucemiantes/efectos adversos , Insulina/efectos adversos , Interleucina-10/sangre , Interleucina-6/sangre , Hígado/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Animales , Regulación de la Expresión Génica/efectos de los fármacos , Hipoglucemia/inducido químicamente , Hipoglucemiantes/farmacología , Insulina/farmacología , Masculino , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
In order to verify the effects of heat and exercise acclimation (HA) on resting and exercise-induced expression of plasma and leukocyte heat shock protein 72 (Hsp72) in humans, nine healthy young male volunteers (25.0 ± 0.7 years; 80.5 ± 2.0 kg; 180 ± 2 cm, mean ± SE) exercised for 60 min in a hot, dry environment (40 ± 0°C and 45 ± 0% relative humidity) for 11 days. The protocol consisted of running on a treadmill using a controlled hyperthermia technique in which the work rate was adjusted to elevate the rectal temperature by 1°C in 30 min and maintain it elevated for another 30 min. Before and after the HA, the volunteers performed a heat stress test (HST) at 50% of their individual maximal power output for 90 min in the same environment. Blood was drawn before (REST), immediately after (POST) and 1 h after (1 h POST) HST, and plasma and leukocytes were separated and stored. Subjects showed expected adaptations to HA: reduced exercise rectal and mean skin temperatures and heart rate, and augmented sweat rate and exercise tolerance. In HST1, plasma Hsp72 increased from REST to POST and then returned to resting values 1 h POST (REST: 1.11 ± 0.07, POST: 1.48 ± 0.10, 1 h POST: 1.22 ± 0.11 ng mL(-1); p < 0.05). In HST2, there was no change in plasma Hsp72 (REST: 0.94 ± 0.08, POST: 1.20 ± 0.15, 1 h POST: 1.17 ± 0.16 ng mL(-1); p > 0.05). HA increased resting levels of intracellular Hsp72 (HST1: 1 ± 0.02 and HST2: 4.2 ± 1.2 density units, p < 0.05). Exercise-induced increased intracellular Hsp72 expression was observed on HST1 (HST1: REST, 1 ± 0.02 vs. POST, 2.9 ± 0.9 density units, mean ± SE, p < 0.05) but was inhibited on HST2 (HST2: REST, 4.2 ± 1.2 vs. POST, 4.4 ± 1.1 density units, p > 0.05). Regression analysis showed that the lower the pre-exercise expression of intracellular Hsp72, the higher the exercise-induced increase (R = -0.85, p < 0.05). In conclusion, HA increased resting leukocyte Hsp72 levels and inhibited exercise-induced expression. This intracellular adaptation probably induces thermotolerance. In addition, the non-increase in plasma Hsp72 after HA may be related to lower stress at the cellular level in the acclimated individuals.