The objectives of this study are threefold: 1) to assess whether 7 days of oral glutamine (GLN) supplementation reduces exercise-induced intestinal permeability; 2) whether supplementation prevents the proinflammatory response; and 3) whether these changes are associated with upregulation of the heat shock response. On separate occasions, eight human subjects participated in baseline testing and in GLN and placebo (PLA) supplementation trials, followed by a 60-min treadmill run. Intestinal permeability was higher in the PLA trial compared with baseline and GLN trials (0.0604 ± 0.047 vs. 0.0218 ± 0.008 and 0.0272 ± 0.007, respectively; P < 0.05). IκBα expression in peripheral blood mononuclear cells was higher 240 min after exercise in the GLN trial compared with the PLA trial (1.411 ± 0.523 vs. 0.9839 ± 0.343, respectively; P < 0.05). In vitro using the intestinal epithelial cell line Caco-2, we measured effects of GLN supplementation (0, 4, and 6 mM) on heat-induced (37° or 41.8°C) heat shock protein 70 (HSP70), heat shock factor-1 (HSF-1), and occludin expression. HSF-1 and HSP70 levels increased in 6 mM supplementation at 41°C compared with 0 mM at 41°C (1.785 ± 0.495 vs. 0.6681 ± 0.290, and 1.973 ± 0.325 vs. 1.133 ± 0.129, respectively; P < 0.05). Occludin levels increased after 4 mM supplementation at 41°C and 6 mM at 41°C compared with 0 mM at 41°C (1.236 ± 0.219 and 1.849 ± 0.564 vs. 0.7434 ± 0.027, respectively; P < 0.001). GLN supplementation prevented exercise-induced permeability, possibly through HSF-1 activation.
Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease that is atherogenic. Decreased arterial distensibility (AD) is a risk factor for cardiovascular disease, and this precursor may be associated with SLE. Accordingly, we tested the hypothesis that patients with SLE will have significantly (p < 0.05) decreased AD when compared to normal, healthy age, and gender matched controls. Noninvasive, high resolution ultrasound was performed on 30 patients with chronic SLE and 16 age and gender matched controls. All were female. Maximum systolic and minimum diastolic diameters (mm) and intima-media thickness (IMT, mm) in the right common carotid artery were measured from M-mode images. In vitro arterial models were used for quality control. With a single, blinded observer, the 95% confidence levels for accuracy and precision for noninvasive systolic and diastolic tonometric arm blood pressures (SBP, DBP) and carotid sonographic diameters were ~5 mmHg and ~0.10 mm, respectively. Derived measurements for strain (%), stiffness (units), and AD (units) were determined by published arterial mechanical models and algorithms. Results (mean/standard deviation) were as follows: (patients/controls; # =p<0.05) Age 39/11, 35/11 years; SBP 130/20, 117/8# mmHg; DBP 82/11, 74/9# mmHg; strain 11/4, 11/4 %); stiffness 19/10, 17/11 units; IMT 0.44/0.08, 0.41/0.06 mm; AD 3.10/1.49, 3.30/1.63 units. There were no statistically significant differences (p<0.05) in measurements of AD and IMT in the common carotid artery between relatively young SLE patients and well matched controls.
Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease that is atherogenic. Arterial distensibility (AD) is a risk factor and an independent predictor of cardiovascular morbidity and mortality. Importantly, AD can be easily determined noninvasively with hand held, portable, low power, and relatively inexpensive equipment. Operator training is required, but minimal. Nevertheless, an association between SLE and AD has not been reported. Accordingly, we tested the hypothesis that patients with SLE would have a significantly (p<0.05) decreased AD when compared to healthy controls. We used noninvasive, high spatial resolution, 10 MHz, image‐guided, M‐mode sonography to measure maximal systolic and minimal diastolic diameters and diastolic intima‐media thickness (IMT) at 3 sites in the right common carotid artery of 17 SLE patients and 51 healthy age and gender matched controls. In the one blinded observer, the 95% confidence levels for accuracy and precision for noninvasive tonometric blood pressures and sonographic diameters were ~5mmHg and ~0.15mm, respectively. The calculated values for AD were determined by standard arterial mechanical models and algorithms. Results are given as X/SD with *= p<0.05 versus controls:These preliminary data suggest that AD is significantly (p<0.05) decreased in young patients with SLE. Thus, arterial distensibility may be an efficient and inexpensive marker of clinically important atherosclerosis in young patients with systemic lupus eyrthematosus.(Funded, in part, by NIHRO1HL077422)
INTRODUCTIONAging is associated with an accumulation of damaged aberrant macromolecules. Autophagy is the process that contributes to the maintenance of cellular homeostasis through degradation and subsequent recycling of damaged proteins and organelles and may be coordinated by the heat shock response. In this pilot study, we tested the hypothesis that aging reduces the heat shock and autophagy responses to heat shock in human peripheral blood mononuclear cells (PBMC).METHODSFour young control (21.25 ± 1.5 years, 3 male, 1 female) and four older subjects (63 ± 2.9 years, 2 male, 2 female) participated in this study. PBMCs were isolated from whole blood and cells were analyzed for baseline levels of LC3‐II and HSP70 proteins. In subsequent studies, PBMCs collected from young and older subjects were exposed to 1 h heat incubation at 42°C, and HSP70 and LC3‐II expression were measured by Western blot analysis and normalized to β‐actin. Densitometric values (mean ± standard deviation) for baseline and heat shock studies are reported.RESULTSSurprisingly, the PBMCs from older subjects had a higher (p < .01) baseline level, 0.64 ± 0.14, of LC3‐II than the younger subjects, 0.07 ± 0.14. An increase (p < .05) in heat shock protein (HSP70) from baseline levels of 0.03 ± 0.07 to 1.77 ± 1.32 following heat shock was found in young subjects, but not older subjects. No within or between group differences were found in LC3‐II following heat shock.CONCLUSIONSContrary to findings in animals, our results suggest that autophagy is increased, not decreased with aging in humans. This increased baseline level may partially compensate for the compromised ability to upregulate HSP70 and stimulate autophagy after a heat stress exposure.
Exercise disrupts homeostasis and leads to the induction of an important catabolic system called autophagy. Autophagy is a beneficial cell survival process that is induced in periods of starvation. The purposes of this study are to (1) determine the time course of autophagy activation following endurance exercise at 70% of VO 2 max in a warm environment and (2) to determine if exercising at 50% of VO 2 max induces autophagy in a warm environment. Methods. Eight endurance trained subjects (2 females) participated in this study and completed a moderate intensity exercise (MIE) trial for 1h (50% of VO 2 max), and a high intensity exercise (HIE) trial for 1h (70% of VO 2 max). Results. Core temperature and heart rate during HIE was higher during 10-60 and 5-60 minutes, respectively, when compared to the same time during MIE and pre-HIE, p < 0.01. IL-6 vi levels were increased (p < 0.01) 0h post-exercise and 1h post-exercise HIE versus preexercise. IL-6 was increased following MIE 0h post-exercise, when compared to preexercise, p < 0.01. Decreases (p < 0.05) in plasma insulin were found following HIE at 2h, when compared to pre-exercise. Decreases in plasma insulin were also found at 4h post-exercise following MIE when compared to pre-exercise, p < 0.05. HIE increased (p < 0.05) autophagy marker LC3-II at 0h , 2h, and 4h post-exercise when compared to preexercise. MIE increased LC3-II at 1h post-exercise when compared to pre-exercise. LC3b decreased following MIE at 1h (p < 0.01) and was increased at 2h, post-exercise when compared to baseline. HSPA1A was decreased at 1h following HIE, when compared to baseline, p < 0.01. HSP70 and LC3-II were moderately and significantly related during MIE, p < 0.01. Increased Akt phosphorylation occurred 2h post-MIE when compared to pre-exercise levels, p < 0.01. Conclusions. Our data suggest that autophagy can be stimulated by exercise at both 50% VO 2 max and 70% VO 2 max. MIE induced phosphorylation of Akt post-exercise and may be activated independent of circulating insulin levels. It is unknown how or if the decreased levels we observed in plasma insulin and increases in IL-6 influence autophagy in PBMCs following exercise.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.