Micah Zuhl

Regulatory Coordination between Two Major Intracellular Homeostatic Systems: HEAT SHOCK RESPONSE AND AUTOPHAGY*

Background: Both autophagy and the heat stress response represent protein management alternatives for the stressed cell. Their inter-relationship is not known. Results: Heat shock factor-1 knockdown increases and HSP70 overexpression inhibits autophagy in cell culture model. Preactivation of heat shock inhibits exercise-induced autophagy in humans. Conclusion: Heat shock response plays a negative role in autophagy regulation. Significance: Heat shock response regulates autophagy. The eukaryotic cell depends on multitiered homeostatic systems ensuring maintenance of proteostasis, organellar integrity, function and turnover, and overall cellular viability. At the two opposite ends of the homeostatic system spectrum are heat shock response and autophagy. Here, we tested whether there are interactions between these homeostatic systems, one universally operational in all prokaryotic and eukaryotic cells, and the other one (autophagy) is limited to eukaryotes. We found that heat shock response regulates autophagy. The interaction between the two systems was demonstrated by testing the role of HSF-1, the central regulator of heat shock gene expression. Knockdown of HSF-1 increased the LC3 lipidation associated with formation of autophagosomal organelles, whereas depletion of HSF-1 potentiated both starvation- and rapamycin-induced autophagy. HSP70 expression but not expression of its ATPase mutant inhibited starvation or rapamycin-induced autophagy. We also show that exercise induces autophagy in humans. As predicted by our in vitro studies, glutamine supplementation as a conditioning stimulus prior to exercise significantly increased HSP70 protein expression and prevented the expected exercise induction of autophagy. Our data demonstrate for the first time that heat shock response, from the top of its regulatory cascade (HSF-1) down to the execution stages delivered by HSP70, controls autophagy thus connecting and coordinating the two extreme ends of the homeostatic systems in the eukaryotic cell.

Exercise regulation of intestinal tight junction proteins

Gastrointestinal distress, such as diarrhoea, cramping, vomiting, nausea and gastric pain are common among athletes during training and competition. The mechanisms that cause these symptoms are not fully understood. The stress of heat and oxidative damage during exercise causes disruption to intestinal epithelial cell tight junction proteins resulting in increased permeability to luminal endotoxins. The endotoxin moves into the blood stream leading to a systemic immune response. Tight junction integrity is altered by the phosphoylation state of the proteins occludin and claudins, and may be regulated by the type of exercise performed. Prolonged exercise and high-intensity exercise lead to an increase in key phosphorylation enzymes that ultimately cause tight junction dysfunction, but the mechanisms are different. The purpose of this review is to (1) explain the function and physiology of tight junction regulation, (2) discuss the effects of prolonged and high-intensity exercise on tight junction permeability leading to gastrointestinal distress and (3) review agents that may increase or decrease tight junction integrity during exercise.

Effects of oral glutamine supplementation on exercise-induced gastrointestinal permeability and tight junction protein expression

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.

Time course of supine and standing shifts in total body, intracellular and extracellular water for a sample of healthy adults

Background/objectives:Traditional tetrapolar bioimpedance spectroscopy (BIS) is performed with the participant supine for 10 min. New vertical analyzers are penetrating clinical, home and fitness markets, but have body water values that differ from supine reference measures. The minimum time standing prior to assessment does not appear in the literature. We investigated the time course of body water shifts in healthy adults undergoing 30-min assessments in supine and vertical positions.Subjects/methods:While seated, participants were prepped for standard tetrapolar electrode placement. Starting position was counterbalanced and body water measurements were taken every 5 min for 30 min in both positions. Participants sat for 2 min prior to switching positions. Of the 64 participants, three were unable to stand for 30 min; their data were excluded. Body size differences were minimized via computation of relative (%) change between time intervals for total body water (TBW), extracellular water (ECW) and intracellular water (ICW).Results:ECW and ICW shifted in opposite directions while participants were supine; as ECW decreased at each time point, ICW increased (P<0.0125). Likewise, when participants stood, ECW increased incrementally (P<0.0125), but the decreases in ICW were not significant. At each time interval, the changes in supine ECW and ICW differed from the standing values (P<0.05). No postural or time differences were found for %change TBW.Conclusions:For TBW, 5 min appears sufficient for fluid stabilization in either position. Supine ECW and ICW stabilization require more than 30 min as does standing ECW.

Carbohydrate gel ingestion during running in the heat on markers of gastrointestinal distress

Abstract The purpose of this study is to measure the effects of carbohydrate ingestion during exercise in the heat by measuring markers of gastrointestinal damage and inflammation. Methods: Active subjects (n = 7) completed two 60-min running trials in a heated environment (70% VO2max, 30°C). At minute 20 of exercise, subjects consumed a carbohydrate gel (Cho) (27 g), or a non-carbohydrate placebo (nCho). Plasma endotoxin, I-FABP, TNF-α, IL-6, IL-1β, IL-10, and MCP-1 were measured pre-exercise, 20-min post-exercise, and again 2-h, and 4-h post-exercise. Results: Endotoxin increased 20-min post-exercise compared to pre in the Cho trial only (p = .03). I-FABP levels increased 20-min post-exercise in the Cho trial only compared to pre-exercise (p = .003). I-FABP levels were also increased in Cho trial 20-min post-exercise when compared to same time point in the nCho trial (p = .032). TNF-α increased 20-min post-exercise in the Cho trial only compared to pre (p = .03). Plasma IL-6 concentration increased 20-min post-exercise when compared to pre in both the Cho (p = .002) and nCho (p = .009), but remained elevated at the 2-h time point in the nCho trial (p = .03). I-FABP and several plasma cytokines (TNF-α, MCP-1, Il-6) returned to baseline sooner in the Cho trial. Conclusions: Ingestion of carbohydrate gel during exercise in the heat enhances markers of gastrointestinal wall damage.

HSP72 Up-regulation with heat acclimation

Comment on: Amorim FT, et al. Insights into the role of heat shock proteins 72 to whole-body heat acclimation in humans. Temperature 2015; 2:499-505; http://dx.doi.org/10.1080/23328940.2015.1110655...

The Effects of a Harness Safety System During Maximal Treadmill Run Testing in Collegiate Middle- and Long-Distance Runners

Abstract Mermier, CM, Zuhl, MN, Wilmerding, MV, Beam, JR, White, AC, Salgado, RM, and Beverly, JM. The effects of a harness safety system during maximal treadmill run testing in collegiate middle- and long-distance runners. J Strength Cond Res 27(11): 2934–2938, 2013—This study compared the results of graded maximal treadmill testing with and without a safety harness (SH) spotting system among collegiate middle- and long-distance runners. Thirteen (n = 8 men, n = 5 women) collegiate runners completed 2 randomly selected maximal treadmill tests. One trial used an SH, and one trial used no harness. All tests were separated by at least 48 hours. The subjects began the test at a velocity of 14.5 or 12 km·h−1 with 1% grade for men and women, respectively, and increased 0.80 kilometers/hr per stage. During each trial, metabolic data and running speed values were recorded along with the completion of a safety questionnaire. No significant difference was found for maximal oxygen consumption (60.84 ± 8.89 vs. 60.733 ± 9.38 ml·kg−1·min−1) and velocity at maximal oxygen consumption (5.33 ± 0.62 vs. 5.24 ± 0.57 m·s−1) between the no harness and harness trials, respectively. Test time was found to be significantly longer in the no harness trial (611.06 ± 119.34 vs. 537.38 ± 91.83 seconds, p < 0.05). The results of the safety questionnaire demonstrated that the runners felt significantly more comfortable during the SH trial (p < 0.05).

Exercise Prescription Techniques in Cardiac Rehabilitation Centers in Midwest States

ABSTRACT Introduction: Cardiac rehabilitation (CR) is a primary prescribed treatment for a variety of cardiovascular disease states, including: coronary artery disease, percutaneous coronary interv...

Objective and subjective measures of exercise intensity during thermo-neutral and hot yoga.

While hot yoga has gained enormous popularity in recent years, owing in part to increased environmental challenge associated with exercise in the heat, it is not clear whether hot yoga is more vigorous than thermo-neutral yoga. Therefore, the aim of this study was to determine objective and subjective measures of exercise intensity during constant intensity yoga in a hot and thermo-neutral environment. Using a randomized, crossover design, 14 participants completed 2 identical ∼20-min yoga sessions in a hot (35.3 ± 0.8 °C; humidity: 20.5% ± 1.4%) and thermo-neutral (22.1 ± 0.2 °C; humidity: 27.8% ± 1.6%) environment. Oxygen consumption and heart rate (HR) were recorded as objective measures (percentage of maximal oxygen consumption and percentage of maximal HR (%HRmax)) and rating of perceived exertion (RPE) was recorded as a subjective measure of exercise intensity. There was no difference in exercise intensity based on percentage of maximal oxygen consumption during hot versus thermo-neutral yoga (30.9% ± 2.3% vs. 30.5% ± 1.8%, p = 0.68). However, exercise intensity was significantly higher during hot versus thermo-neutral yoga based on %HRmax (67.0% ± 2.3% vs. 60.8% ± 1.9%, p = 0.01) and RPE (12 ± 1 vs. 11 ± 1, p = 0.04). According to established exercise intensities, hot yoga was classified as light-intensity exercise based on percentage of maximal oxygen consumption but moderate-intensity exercise based on %HRmax and RPE while thermo-neutral yoga was classified as light-intensity exercise based on percentage of maximal oxygen uptake, %HRmax, and RPE. Despite the added hemodynamic stress and perception that yoga is more strenuous in a hot environment, we observed similar oxygen consumption during hot versus thermo-neutral yoga, classifying both exercise modalities as light-intensity exercise.

Dance as a treatment for neurological disorders

Abstract Dance has been explored as a therapeutic intervention because of its unique combination of exercise, music and cognitive engagement. Dance therapy is a specific form of dance-based treatment that focuses on how movement correlates with psychological aspects such as self-awareness, expression and coordination, which culminate in a mind–body treatment. In recent years, dance-based programmes have been used as an intervention to improve symptoms of neurological diseases/disorders. Positive results have been shown for patients suffering from Parkinson’s disease, dementia and depression. The neurological adaptations such as improved neural activity and neurogenesis are induced by the combination of coordinated movement strategies, exercise, musical arrangements and social interactions (partnering). With the continued growth of dance therapy, the purpose of this review is to explain the recently proposed theories of how neural changes are mediated through dance, and discuss the positive effects on those suffering from neurological disorders.