Effects of resistance training on heat shock response (HSR), HSP70 expression, oxidative stress, inflammation, and metabolism in middle-aged people

Resistance training (RT) can increase the heat shock response (HSR) in the elderly. As middle-aged subjects already suffer physiological declines related to aging, it is hypothesized that RT may increase the HSR in these people. To assess the effects of resistance training on heat shock response, intra and extracellular HSP70, oxidative stress, inflammation, body composition, and metabolism in middle-aged subjects. Sixteen volunteers (40 – 59 years) were allocated to two groups: the trained group (n = 7), which performed 12 weeks of RT; and the physically inactive—control group (n = 9), which did not perform any type of exercise. The RT program consisted of 9 whole-body exercises (using standard gym equipment) and functional exercises, carried out 3 times/week. Before and after the intervention, body composition, muscle mass, strength, functional capacity, and blood sample measurements (lipid profile, glucose, insulin, oxidative damage, TNF-α, the HSR, HSP70 expression in leukocytes, and HSP72 in plasma) were performed. The HSR analysis demonstrated that this response is maintained at normal levels in middle-aged people and that RT did not cause any improvement. Also, RT increases muscle mass, strength, and functional capacity. Despite no additional changes of RT on the antioxidant defenses (catalase, glutathione peroxidase, and reductase) or inflammation, lipid peroxidation was diminished by RT (group x time interaction, p = 0.009), indicating that other antioxidant defenses may be improved after RT. HSR is preserved in middle-aged subjects without metabolic complications. In addition, RT reduces lipid peroxidation and can retard muscle mass and strength loss related to the aging process. (AU)

Effects of resistance training on heat shock response (HSR), HSP70 expression, oxidative stress, inflammation, and metabolism in middle-aged people

Resistance training (RT) can increase the heat shock response (HSR) in the elderly. As middle-aged subjects already suffer physiological declines related to aging, it is hypothesized that RT may increase the HSR in these people. To assess the effects of resistance training on heat shock response, intra and extracellular HSP70, oxidative stress, inflammation, body composition, and metabolism in middle-aged subjects. Sixteen volunteers (40 – 59 years) were allocated to two groups: the trained group (n = 7), which performed 12 weeks of RT; and the physically inactive—control group (n = 9), which did not perform any type of exercise. The RT program consisted of 9 whole-body exercises (using standard gym equipment) and functional exercises, carried out 3 times/week. Before and after the intervention, body composition, muscle mass, strength, functional capacity, and blood sample measurements (lipid profile, glucose, insulin, oxidative damage, TNF-α, the HSR, HSP70 expression in leukocytes, and HSP72 in plasma) were performed. The HSR analysis demonstrated that this response is maintained at normal levels in middle-aged people and that RT did not cause any improvement. Also, RT increases muscle mass, strength, and functional capacity. Despite no additional changes of RT on the antioxidant defenses (catalase, glutathione peroxidase, and reductase) or inflammation, lipid peroxidation was diminished by RT (group x time interaction, p = 0.009), indicating that other antioxidant defenses may be improved after RT. HSR is preserved in middle-aged subjects without metabolic complications. In addition, RT reduces lipid peroxidation and can retard muscle mass and strength loss related to the aging process. (AU)

Potencial rol protector del óxido nítrico y Hsp70 asociado a alimentos funcionales en la aterosclerosis / Potential protective role of nitric oxide and Hsp70 linked to functional foods in the atherosclerosis

En la actualidad se encuentran en constante revisión los mecanismos determinantes primarios y las posibles terapéuticas de una de las principales entidades patológicas considerada epidémica y constituida como problema de salud pública mundial: la aterosclerosis. En tal sentido, pacientes que la padecen presentan como común denominador disfunción mitocondrial, estrés oxidativo e inflamación. De especial interés, el óxido nítrico, un conocido gas mensajero vasoactivo, ha sido estrechamente relacionado con el proceso inflamatorio, oxidativo y disfuncional mitocondrial propio de la aterosclerosis. Por otro lado, muy recientemente se ha demostrado que alteraciones en la biodisponibilidad del óxido nítrico inducirían la expresión de proteínas de shock térmico. Este mecanismo sería inducido también por el uso de los denominados alimentos funcionales como estrategia para prevenir el envejecimiento vascular así como el desarrollo de aterosclerosis. Finalmente, el mayor conocimiento de los mecanismos implicados en el desarrollo de la aterosclerosis nos permitirá proponer nuevas y posibles intervenciones higiénicas, sanitarias y terapéuticas

Atherosclerosis, one of the main pathologic entities considered epidemic and a worldwide public health problem, is currently under constant review as regards its basic determining mechanisms and therapeutic possibilities. In this regard, all patients afflicted with the disease exhibit mitochondrial dysfunction, oxidative stress and inflammation. Interestingly, nitric oxide - a known vasoactive messenger gas - has been closely related to the inflammatory, oxidative and mitochondrial dysfunctional process that characterizes atherosclerosis. In addition, it has recently been demonstrated that alterations in the bioavailability of nitric oxide would induce the expression of heat shock proteins. This agrees with the use of functional foods as a strategy to prevent both vascular aging and the development of atherosclerosis. Finally, a greater knowledge regarding the mechanisms implied in the development of atherosclerosis will enable proposing new and possible hygiene, health and therapeutic interventions

Fine particulate matter potentiates type 2 diabetes development in high-fat diet-treated mice: stress response and extracellular to intracellular HSP70 ratio analysis

Exposure to fine particulate matter (PM2.5) air pollution is a risk factor for type 2 diabetes (T2DM). We argue whether the potentiating effect of PM2.5 over the development of T2DM in high-fat diet (HFD)-fed mice would be related to modification in cell stress response, particularly in antioxidant defenses and 70-kDa heat shock proteins (HSP70) status. Male mice were fed standard chow or HFD for 12 weeks and then randomly exposed to daily nasotropic instillation of PM2.5 for additional 12 weeks under the same diet schedule, divided into four groups (n = 14-15 each): Control, PM2.5, HFD, and HFD + PM2.5 were evaluated biometric and metabolic profiles of mice, and cellular stress response (antioxidant defense and HSP70 status) of metabolic tissues. Extracellular to intracellular HSP70 ratio ([eHSP72]/[iHSP70]), viz. H-index, was then calculated. HFD + PM2.5 mice presented a positive correlation between adiposity, increased body weight and glucose intolerance, and increased glucose and triacylglycerol plasma levels. Pancreas exhibited lower iHSP70 expression, accompanied by 3.7-fold increase in the plasma to pancreas [eHSP72]/[iHSP70] ratio. Exposure to PM2.5 markedly potentiated metabolic dysfunction in HFD-treated mice and promoted relevant alteration in cell stress response assessed by [eHSP72]/[iHSP70], a relevant biomarker of chronic low-grade inflammatory state and T2DM risk (AU)

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Proteínas de choque térmico en la cardioprotección del consumo moderado regular de alcohol / Role of heat shock proteins in the cardioprotection of regular moderate alcohol consumption

Fundamento y objetivos: Estudiar si el efecto cardioprotector del consumo regular de alcohol puede explicarse a través de las heat shock proteins (HSP, «proteínas de choque térmico»), dado su papel etiopatogénico en la ateroesclerosis. Material y métodos: Estudio epidemiológico trasversal en 452 sujetos de 40-60 años de ambos sexos. Se realizó la historia clínica incluyendo frecuencia del consumo medio de alcohol y análisis bioquímicos, y se estatificó el grado de riesgo coronario según la Task Force. Se cuantificaron HSPA1A intracelular, HSPA1A y HSPD1 séricas y anti-Hsp70 y anti-Hsp60 por ELISA. Resultados: Doscientos treinta y ocho (52,7%) sujetos eran abstemios o bebedores de < 20 g/d de alcohol; 123 (27,2%) bebían 20-40 g/d, 66 (14,6%) 40-60 g/d y 25 > 60 g/d (5,5%). Doscientos treinta y nueve carecían de factores de riesgo vascular (RV) o tenían un RV < 5%; 161 tenían RV moderado (10-20%) y 52 presentaban enfermedad ateroesclerótica instaurada. Los bebedores de 40-60 g/d presentaron máximas concentraciones de HSPA1A intracelular, no significativas en RV moderado. HSPA1A sérica no presentó diferencias y HSPD1 fue indetectable. Los bebedores de 40-60 g/d y RV moderado o enfermedad ateroesclerótica presentaron las menores concentraciones de anti-Hsp70. Los anti-Hsp60 fueron máximos en varones bebedores de > 60 g/d y en mujeres bebedoras de 40-60 g/d, especialmente en RV moderado. Conclusiones: El efecto cardioprotector del consumo de 40-60 g/d de alcohol podría deberse, al menos en parte, al incremento de HSPA1A intracelular, potente proteína antiinflamatoria. El consumo excesivo regular de alcohol se asocia a un aumento de anticuerpos anti-Hsp60, estimulantes de citocinas proinflamatorias; ello podría explicar la mortalidad por enfermedad cardiovascular en estos pacientes. Se ha propuesto la aplicación clínica del seguimiento de anticuerpos anti-Hsp en pacientes en riesgo para detectar enfermedad ateroesclerótica (AU)

Background and objectives: To study whether the cardioprotective effect of regular alcohol consumption can be explained by the heat shock proteins (HSP), given their pathogenic role in atherosclerosis. Material and methods: Cross-sectional epidemiological study on 452 men and women aged 40-60. Clinical history, epidemiological survey (frequency of average alcohol consumption) and biochemical analysis was performed; Task Force Chart was applied for classification according to the risk of vascular disease. Intracellular HSPA1A, circulating HSPA1A and HSPD1, and anti-Hsp70/anti-Hsp60 antibodies were quantified by ELISA. Results: Two hundred and thirty-eight (52.7%) were abstemious or drank < 20 g/d of alcohol; 123 (27.2%) drank 20-40 g/d, 66 (14.6%) 40-60 g/d and 25 > 60 g/d (5.5%). Two hundred and thirty-nine had no vascular risk (VR) factor or a risk < 5%, 161 had moderate VR (10-20%) and 52 had established atherosclerotic disease. Drinkers of 40-60 g/d showed the highest concentrations of intracellular HSPA1A, which were not significant in subjects with moderate VR. Extracellular HSPA1A didn’t differ and HSPD1 was undetectable. Drinkers of 40-60 g/d and moderate VR or atherosclerotic disease presented the lowest concentrations of anti-Hsp70. The highest levels of serum anti-Hsp60 were shown in heavy male drinkers of > 60 g/d especially in subjects with moderate VR, and female drinkers of 40-60 g/d. Conclusions: The cardioprotective effect of 40-60 g/d of alcohol consumption could be due in part, to increased intracellular HSPA1A, a potent anti-inflammatory protein. Excessive intake of alcohol increases antibodies anti-Hsp60, stimulating proinflammatory cytokines. This fact may explain the mortality from cardiovascular disease in heavy drinkers. The clinical application of antibody anti-Hsps quantification has been proposed in patients at risk in order to detect atherosclerotic disease (AU)

Hsp70 plays an important role in high-fat diet induced gestational hyperglycemia in mice

Gestational diabetes mellitus (GDM) has emerged as an epidemic disease during the last decade, affecting about 2 to 5 % pregnant women. Even among women who have gestational hyperglycemia may also be positively related to adverse outcomes as GDM. Since heat shock protein (Hsp) 70 has been reported to be associated with diabetes and insulin resistance and its expression was reported to be negatively regulated by the membrane-permeable Hsp70 inhibitor MAL3-101 while positively regulated by the Hsp70 activator BGP-15, we investigated whether Hsp70 played a role in a gestational hyperglycemia mouse model. Mice were divided into non-pregnant and pregnant groups, and each comprised three subgroups: control, high-fat diet (HFD) + MAL3-101, and HFD + BGP-15. We examined the serum levels of triglycerides, total cholesterol, glucose, and insulin, as well as conducted thermal detection of brown adipose tissue (BAT). The role of Hsp70 in BAT apoptosis was also investigated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and caspase-3 staining. Higher serum level of Hsp70 was associated with increased bodyweight gain after pregnancy in mice fed HFD. Circulating Hsp70 was elevated in control pregnant mice compared to control non-pregnant mice. BGP-induced serum Hsp70 expression reduced triglycerides, total cholesterol, glucose, and insulin levels in the serum. Additionally, thermal detection of BAT, TUNEL, and caspase-3 staining revealed relationship correlation between Hsp70 and BAT functions. Hsp70 level is associated with hyperglycemia during pregnancy. Our results support the role of Hsp70 in facilitating BAT activities and protecting BAT cells from apoptosis via caspase-3 pathway

Carboxy terminus of heat shock protein (HSP) 70-interacting protein (CHIP) inhibits HSP70 in the heart

Heat shock protein (HSP) 70 plays a critical role in protecting the heart from various stressor-induced cell injuries; the mechanism remains to be further understood. The present study aims to elucidate the effect of a probiotics-derived protein, LGG-derived protein p75 (LGP), in alleviating the ischemia/reperfusion (I/R)-induced heart injury. We treated rats with the I/R with or without preadministration with LGP. The levels of HSP70 and carboxy terminus of HSP70-interacting protein (CHIP) in the heart tissue were assessed by enzyme-linked immunosorbent assay (ELISA) and Western blotting. The effect of CHIP on suppression of HSP70 and the effect of LGP on suppression of CHIP were investigated with an I/R rat model and a cell culture model. The results showed that I/R-induced infarction in the heart could be alleviated by pretreatment with LGP. HSP70 was detected in naïve rat heart tissue extracts. I/R treatment significantly suppressed the level of HSP70 and increased the levels of CHIP in the heart. A complex of CHIP/HSP70 was detected in heart tissue extracts. The addition of recombinant CHIP to culture inhibited HSP70 in heart cells. LGP was bound CHIP in heart cells and prevented the CHIP from binding HSP70. In summary, I/R can suppress HSP70 and increase CHIP in heart cells. CHIP can suppress HSP70 that can be prevented by pretreatment with LGP. The results imply that CHIP may be a potential target in the prevention of I/R-induced heart cell injury (AU)

Changes in lymphocyte HSP70 levels in women handball players throughout 1 year of training: the role of estrogen levels

Heat shock protein 70 (HSP70) is a chaperone that maintains protein conformation during heat stress. It has recently been observed that HSP70 may be released from cells in response to increased energy demand (e.g., exercise) and/or oxidative stress. Since HSP70 levels should change in response to athletic training, we have investigated whether blood HSP70 levels in young women handball players change over a complete training season. Thirty women handball players (12-24 years old) were divided into (..) (AU)

Proteínas de choque térmico 70kDa en estrés quirúrgico: toracotomía vs herniorrafia / 70kDa heat-shock proteins in surgical stress: thoracotomy vs. Herniorrhaphy

Introducción: Como consecuencia de los procedimientos quirúrgicos, se produce una respuesta de estrés oxidativo con liberación de citoquinas y especies reactivas de oxígeno que activan la Heat Shock Response (HSR, ‘respuesta de choque térmico’) o respuesta al estrés, con un incremento en la síntesis de Heat Shock Proteins (HSP, ‘proteínas de choque térmico’). Objetivo: Estudiar la biología de las Hsps70 intraleucocitarias y la IL-6 como posibles biomarcadores de la inflamación postquirúrgica, y una potencial respuesta anti-Hsp70, en pacientes sometidos a 2 situaciones quirúrgicas de distinta intensidad. Material y métodos: Estudio longitudinal de cohortes, con un grupo de pacientes sometidos a toracotomía bajo anestesia general (n=11), un grupo de pacientes sometidos a herniorrafia inguinal bajo anestesia locoregional (n=10) y un grupo de donantes voluntarios sanos (n=6). Se analizaron Hsps70 intraleucocitarias, Ac anti-hsp70 e IL-6 inmediatamente antes y a las 24h de la cirugía. Resultados: Los pacientes toracotomizados mostraron una disminución significativa de Hsp70 intraleucocitaria y de Ac anti-Hsp70 en el postoperatorio inmediato. Los pacientes con mayores descensos de Hsp70 postoperatoria presentaron diversas complicaciones postquirúrgicas. Ambos grupos presentaron un significativo aumento postoperatorio de los niveles de IL-6. Conclusiones: Cuanto más agresiva es la cirugía, mayor reducción de Hsp70 se produce en el postoperatorio, especialmente en pacientes con peor evolución, lo que ha llevado a proponer a la Hsp70 como marcador pronóstico postquirúrgico. El significativo incremento de IL-6 en ambos grupos, permite concluir que la dispar respuesta al estrés quirúrgico entre ambos grupos se debe no a la respuesta inflamatoria sistémica, sino a la HSR (AU)

Introduction: During and after surgical procedures, there is an oxidative stress response that releases cytokines and reactive oxygen species. This can activate Heat Shock Response (HSR), leading to an increase in Heat Shock Proteins (HSPs) expression proportional to the intensity of the stimulus. Objective: This study examined the biology of intraleucocyte Hsps70 and IL-6 as potential biomarkers of postoperative inflammatory stress, and a potential antiHsp70 autoimmune reaction in patients undergoing two surgical procedures of different severity. Material and methods: Longitudinal cohort study including a group of patients undergoing thoracotomy under general anaesthesia (n=11), a group of patients undergoing inguinal hernia repair under regional anaesthesia (n=10), and a group of healthy controls (n=6). Intraleucocyte Hsps70, antiHsp70 antibodies and IL-6 were analysed, just before and 24h after surgery. Results: Patients undergoing thoracotomy showed a significant decrease in intraleucocyte Hsp70 and antiHsp70 antibodies in the early postoperative period; patients with the greatest Hsp70 decreases after surgery showed the lowest pre-surgical Hsp70 levels and these patients also experienced various postoperative complications. A significant postoperative increase in IL-6 levels in both groups was observed. Conclusions: Patients undergoing a more aggressive surgery showed a significant Hsp70 reduction in the postoperative period. Patients with the lowest values of Hsp70 in the immediate postoperative period had the worst clinical course, which has led to propose use of Hsp70 as a prognostic post-surgical marker. The postoperative decrease in intracellular Hsp70 is parallel to the decrease in circulating autoantibodies. The different response of both groups to surgical stress is not due to systemic inflammatory response, but to HSR (AU)

Effects of the disruption of the HSP70-II gene on the growth, morphology, and virulence of Leishmania infantum promastigotes

The 70-kDa heat shock protein (HSP70) is highly conserved among both prokaryotes and eukaryotes and plays essential roles in diverse cellular functions not only under stress but also under normal conditions. In the protozoan Leishmania infantum, the causative agent of visceral leishmaniasis, HSP70 is encoded by two HSP70 genes. Here, we describe the phenotypic alterations of HSP70-II-deficient (Deltahsp70-II) promastigotes. The absence of HSP70-II caused a major alteration in growth as the promastigotes reached stationary phase. In addition, aberrant forms were frequently observed in Deltahsp70-II mutant cultures. An accumulation of cells in the G2/M phase in cultures of the Deltahsp70-II mutant was determined by flow cytometry. Furthermore, Deltahsp70-II promastigotes showed a limited capacity of multiplication within macrophages, even though attachment to and uptake by macrophages did not differ significantly from the wild-type. Moreover, Deltahsp70-II was highly attenuated in BALB/c mouse experimental infections. In mutants re-expressing HSP70-II, the growth rate was restored, the normal morphology was recovered, and interactions with macrophages increased. However, promastigotes re-expressing HSP70-II did not recover their virulence. Overall, these data highlight the essential role played by HSP70-II expression in Leishmania virulence, pointing to this gene as a promising target for therapeutic interventions (AU)

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Identificación de epítopes T citotóxicosrestringidos a la molécula HLA-A2.1 en laproteína HSP70 de T. cruzi / Identification of HLA-A2.1 restricted CTLs epitopes in the T. cruzi HSP70 protein

El análisis de la capacidad de unión a células T2 realizado con 31 péptidos correspondientes a distintas regiones de la proteína HSP70 de Trypanosoma cruzi, muestra que 14 de estos péptidos tienen una alta o media afinidad por la molécula presentadora A2.1. Interesantemente, el presente manuscrito pone de manifiesto que la inmunización de ratones transgénicos A2/Kb con la proteína recombinante HSP70 de T. cruzi induce CTLs que reconocen células EL4A2/Kb cargadas de forma independiente con tres de los péptidos con afinidad de unión a moléculas A2. Estos péptidos presentan una homología menor del 65 por ciento con sus homólogos de la proteína HSP70 humana. Los resultados obtenidos permiten sugerir la posibilidad de que la HSP70 de T. cruzi pueda ser usada como diana para inducir actividad inmune citotóxica en humanos (AU)

Expresión y localización de hsp70 y hsp27 en pacientes con cáncer de mama / Expression and localization of hsp70 and hsp27 in human breast tumors

Planteamiento: se ha estudiado la inducción de las proteínas de choque térmico (hsp) 70 y 27 en 35 pacientes con cáncer de mama comparando con tumores malignos.Material y métodos: Se han hecho estudios con inmunohistoquímica sobre cortes de parafina de los 35 pacientes con cáncer de mama empleando anticuerpos frente a las proteínas hsp70 y hsp27. Al mismo tiempo se han analizado los tumores, pero no sucede lo mismo con hsp27. La expresión de hsp70 es alta en todos los casos, con más del 60 por ciento de células teñidas por campo en cada tumor. La expresión de hsp27 es menor en los casos dende hay reacción positiva. La expresión de hsp70 parece estar relacionada con los procesos de proliferación en tejido mamario, mientras que en tumores malignos hay una localización nuclear de hsp70.Conclusiones: Se puede decir que los resultados del trabajo apoyan el empleo de hsp70 como marcador de malignidad en el cáncer de mama, dada su expresión aumnetada y translocación nuclear relacionada con el cáncer (AU)