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Activation of an appropriate innate immune response to bacterial infection is critical to limit microbial spread and generate cytokines and chemokines to instruct appropriate adaptive immune responses. Recognition of bacteria or bacterial products by pattern recognition molecules is crucial to initiate this response. However, it is increasingly clear that the context in which this recognition occurs can dictate the quality of the response and determine the outcome of an infection. The cross talk established between host and pathogen results in profound alterations on cellular homeostasis triggering specific cellular stress responses. In particular, the highly conserved integrated stress response (ISR) has been shown to shape the host response to bacterial pathogens by sensing cellular insults resulting from infection and modulating transcription of key genes, translation of new proteins and cell autonomous antimicrobial mechanisms such as autophagy. Here, we review the growing body of evidence demonstrating a role for the ISR as an integral part of the innate immune response to bacterial pathogens.
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The purpose of the present study was to examine the effects of a high- or low-carbohydrate (CHO) diet on performance, aerobic and anaerobic contribution, and metabolic responses during supramaximal exercise. Six physically-active men first performed a cycling exercise bout at 115% maximal oxygen uptake to exhaustion after following their normal diet for 48 h (â¼50% of CHO, control test). Seventy-two hours after, participants performed a muscle glycogen depletion exercise protocol, followed by either a high- or low-CHO diet (â¼70 and 25% of CHO, respectively) for 48 h, in a random, counterbalanced order. After the assigned diet period (48 h), the supramaximal cycling exercise bout (115% maximal oxygen consumption) to exhaustion was repeated. The low-CHO diet reduced time to exhaustion when compared with both the control and the high-CHO diet (-19 and -32%, respectively, p < 0.05). The reduced time to exhaustion following the low-CHO diet was accompanied by a lower total aerobic energy contribution (-39%) compared with the high-CHO diet (p < 0.05). However, the aerobic and anaerobic energy contribution at the shortest time to exhaustion (isotime) was similar among conditions (p > 0.05). The low-CHO diet was associated with a lower blood lactate concentration (p < 0.05), with no effect on the plasma concentration of insulin, glucose and K(+) (p > 0.05). In conclusion, a low-CHO diet reduces both performance and total aerobic energy provision during supramaximal exercise. As peak K(+) concentration was similar, but time to exhaustion shorter, the low-CHO diet was associated with an earlier attainment of peak plasma K(+) concentration.
Assuntos
Carboidratos da Dieta , Esforço Físico , Dieta , Carboidratos da Dieta/metabolismo , Exercício Físico , Humanos , Consumo de OxigênioRESUMO
Exercise training (ET) is a coadjuvant therapy in preventive cardiology. It delays cardiac dysfunction and exercise intolerance in heart failure (HF); however, the molecular mechanisms underlying its cardioprotection are poorly understood. We tested the hypothesis that ET would prevent Ca(2+) handling abnormalities and ventricular dysfunction in sympathetic hyperactivity-induced HF mice. A cohort of male wild-type (WT) and congenic alpha(2A)/alpha(2C)-adrenoceptor knockout (alpha(2A)/alpha(2C)ARKO) mice with C57BL6/J genetic background (3-5 mo of age) were randomly assigned into untrained and exercise-trained groups. ET consisted of 8-wk swimming session, 60 min, 5 days/wk. Fractional shortening (FS) was assessed by two-dimensional guided M-mode echocardiography. The protein expression of ryanodine receptor (RyR), phospho-Ser(2809)-RyR, sarcoplasmic reticulum Ca(2+) ATPase (SERCA2), Na(+)/Ca(2+) exchanger (NCX), phospholamban (PLN), phospho-Ser(16)-PLN, and phospho-Thr(17)-PLN were analyzed by Western blotting. At 3 mo of age, no significant difference in FS and exercise tolerance was observed between WT and alpha(2A)/alpha(2C)ARKO mice. At 5 mo, when cardiac dysfunction is associated with lung edema and increased plasma norepinephrine levels, alpha(2A)/alpha(2C)ARKO mice presented reduced FS paralleled by decreased SERCA2 (26%) and NCX (34%). Conversely, alpha(2A)/alpha(2C)ARKO mice displayed increased phospho-Ser(16)-PLN (76%) and phospho-Ser(2809)-RyR (49%). ET in alpha(2A)/alpha(2C)ARKO mice prevented exercise intolerance, ventricular dysfunction, and decreased plasma norepinephrine. ET significantly increased the expression of SERCA2 (58%) and phospho-Ser(16)-PLN (30%) while it restored the expression of phospho-Ser(2809)-RyR to WT levels. Collectively, we provide evidence that improved net balance of Ca(2+) handling proteins paralleled by a decreased sympathetic activity on ET are, at least in part, compensatory mechanisms against deteriorating ventricular function in HF.