IRBIT a Master Regulator of Cell Physiology

(excerpt) Hormones and neurotransmitters regulate cell functions by binding to their receptors, which activate intracellular signaling and produce the physiological response [1]. There are several intracellular pathways, including but not limited to, leading to the activation of protein kinases, phosphatases and increase in intracellular calcium (Ca2+) [1]

Effect of inflammatory cytokines and high fat diet on inositol-1,4,5-trisphosphate (IP3) receptors binding protein released with IP3 (IRBIT) expression in intestinal cells

IP3, upon binding to the IP3 receptor (IP3R), causes the release of intracellular calcium from the endoplasmic reticulum, which drives many cellular responses (e.g., cell spreading, exocytosis). In addition to releasing calcium, IP3 also causes the release of IRBIT from the IP3R. Over the past decade, IRBIT has been described as a protein that regulates calcium release, due to interaction with the IP3R, the activity of the Na-HCO3 cotransporter, the cystic fibrosis transmembrane regulator, and the Na/H exchanger (NHE3). Lack of reabsorption of Na+ by NHE3 in the intestine is responsible for diarrhea. Recently it was shown that IRBIT and NHE3 expression was decreased in a mouse model of diabetes, and the loss of NHE3 expression induced diarrhea in this model. Insulin treatment restored IRBIT and NHE3 expression, resulting in a decrease of diarrhea. Besides insulin, very little is known about factors regulating IRBIT expression in intestinal epithelial cells. In this work, we set to study the effect of inflammatory cytokines and high calorie diet on IRBIT expression, due to the fact that diabetes is associated with chronic inflammation and high caloric intake. To test the effect of inflammatory cytokines, we used the human colonic crypt cells T84. Exposing T84 cells to interleukin 13 or tumor necrosis factor alpha for 72 hours decreased IRBIT expression by 36% (P \u3c 0.001, n = 5) and 44% (P \u3c 0.001, n = 3) respectively. Finally, we compared the expression of IRBIT in mice fed with low fat milk (control) versus high milk fat (37%). We found that in the duodenum of 3 mice with a high fat diet, a substantial increase of IRBIT expression compared to the control. Our work is the first to demonstrate that inflammatory cytokines and dietary fat can alter IRBIT expression

IRBIT a Master Regulator of Cell Physiology

(excerpt) Hormones and neurotransmitters regulate cell functions by binding to their receptors, which activate intracellular signaling and produce the physiological response [1]. There are several intracellular pathways, including but not limited to, leading to the activation of protein kinases, phosphatases and increase in intracellular calcium (Ca2+) [1]

Elucidating internalization mechanism of the Na-K-2Cl cotransporter 1 and its fate in the endocytotic pathway during protein kinase C activation in epithelial cells

Gut clearance (i.e., fluid secretion) is an important mechanism for host defense. Fluid secretion flushes luminal toxins and prevents bacterial attachment to intestinal epithelial cells, which otherwise would harm the host. In the colon, transepithelial chloride fluid secretion drives fluid secretion. The basolateral Na-K-2Cl cotransporter 1 (NKCC1) is the main protein pumping chloride inside the cell for its secretion by apical chloride channels. Previous studies have demonstrated that activation of the protein kinase C (PKC) causes a rapid internalization of NKCC1, thus decreasing chloride secretion. To date, the protein kinase C downstream targets involved in NKCC1 internalization and the fate of NKCC1 in the endocytic pathway is unknown. Using the human colonic crypt cells T84, we demonstrate that T84 cells express α-adducin and Myristoylated, Alanine-Rich C Kinase Substrate, two substrates of the PKC involved in protein internalization in other cells. In presence of phorbol 12-myristate 13-acetate (PMA), an activator of the conventional and novel PKC, we demonstrate that α-adducin is strongly phosphorylated in T84 cells. Next, we hypothesized that upon activation by PKC, α-adducin binds to NKCC1. In T84 cells subjected to PMA, we show that phospho α-adducin co-immunoprecipitates with NKCC1. Next, we used Mardin Darby Canine Kidney (MDCK) cells stably expressing eGFP-NKCC1. In this model, using immunocytochemistry, we show that NKCC1 colocalizes with α-adducin at the plasma membrane during PKC activation. Finally, we tested the fate of NKCC1 in the endocytic pathway. In MDCK cells exposed to PMA, we found that NKCC1 colocalizes with LAMP1, a marker of the lysosome. In conclusion, our data suggest that α-adducin participates to NKCC1 internalization during PKC activation and NKCC1 is targeted for degradation

Improvement Rates in Aerobic and Anaerobic Training

The purpose of this research study was to determine the difference in improvement rates between anaerobic and aerobic training. Over two, four week periods VO2max test and Wingate test were administered on 11 untrained students from a Northwest College. The hypothesis was anaerobic training would facilitate greater improvement rates in both VO2max accessed through use of metabolic cart and anaerobic performance assessed through use of a Wingate test. Depending on what systems an individual wants to improve in performance they should specifically stress the desired system. Overall participants who trained aerobically had a 13.01% average improvement (p=0.275) in the VO2max test compared to 8.18% average improvement (p=0.579) in the Wingate test. Participants who trained anaerobically had a 3.77% average improvement in VO2max (p=0.744) and also a 6.39% improvement (p=0.667) anaerobic performance. In conclusion, the statistical hypothesis was rejected because anaerobic training did not produce the most beneficial results due to training. The anaerobic training only had improvement in the Wingate test while the aerobic training had the biggest effect on the VO2max test. Results from this study indicate that individuals can improve at a faster rate in both aerobic and anaerobic capacity with aerobic training

Serum Endocannabinoid and Mood Changes after Exercise in Major Depressive Disorder

MEYER, J. D., K. M. CROMBIE, D. B. COOK, C. J. HILLARD, and K. F. KOLTYN. Serum Endocannabinoid and Mood Changes after Exercise in Major Depressive Disorder. Med. Sci. Sports Exerc., Vol. 51, No. 9, pp. 1909–1917, 2019. The endocannabinoid (eCB) system is implicated in the pathophysiology of depression and is responsive to acute exercise in healthy adults. Purpose: We aimed to describe acute changes in serum eCB across a prescribed moderate (MOD) and a self-selected/preferred (PREF) intensity exercise session in women with major depressive disorder (MDD) and determine relationships between changes in eCB and mood states. Methods: Women with MDD (n = 17) exercised in separate sessions for 20 min on a cycle ergometer at both MOD or PREF in a within-subjects design. Blood was drawn before and within 10 min after exercise. Serum concentrations of eCB (anandamide [AEA], 2-arachidonoylglycerol) and related lipids (palmitoylethanolamine, oleoylethanolamine, 2-oleoylglycerol) were quantified using stable isotope-dilution, liquid chromatography/mass spectrometry/mass spectrometry. The profile of mood states and state-trait anxiety inventory (state only) were completed before, 10 min and 30 min postexercise. Results: Significant elevations in AEA (P = 0.013) and oleoylethanolamine (P = 0.024) occurred for MOD (moderate effect sizes: Cohen’s d = 0.58 and 0.41, respectively). Significant (P \u3c 0.05) moderate negative associations existed between changes in AEA and mood states for MOD at 10 min (depression, confusion, fatigue, total mood disturbance [TMD] and state anxiety) and 30 min postexercise (confusion, TMD and state anxiety). Significant (P \u3c 0.05) moderate negative associations existed between 2-arachidonoylglycerol and mood states at 10 min (depression and confusion) and 30 min postexercise (confusion and TMD). Changes in eCB or related lipids or eCB–mood relationships were not found for PREF. Conclusion: Given the broad, moderate–strength relationships between improvements in mood states and eCB increases after MOD, it is plausible that the eCB system contributes to the mood-enhancing effects of prescribed acute exercise in MDD. Alternative mechanisms are likely involved in the positive mood state effects of preferred exercis

Exercise Strengthens Central Nervous System Modulation of Pain in Fibromyalgia

To begin to elucidate the mechanisms underlying the benefits of exercise for chronic pain, we assessed the influence of exercise on brain responses to pain in fibromyalgia (FM). Complete data were collected for nine female FM patients and nine pain-free controls (CO) who underwent two functional neuroimaging scans, following exercise (EX) and following quiet rest (QR). Brain responses and pain ratings to noxious heat stimuli were compared within and between groups. For pain ratings, there was a significant (p \u3c 0.05) Condition by Run interaction characterized by moderately lower pain ratings post EX compared to QR (d = 0.39–0.41) for FM but similar to ratings in CO (d = 0.10–0.26), thereby demonstrating that exercise decreased pain sensitivity in FM patients to a level that was analogous to pain-free controls. Brain responses demonstrated a significant within-group difference in FM patients, characterized by less brain activity bilaterally in the anterior insula following QR as compared to EX. There was also a significant Group by Condition interaction with FM patients showing less activity in the left dorsolateral prefrontal cortex following QR as compared to post-EX and CO following both conditions. These results suggest that exercise appeared to stimulate brain regions involved in descending pain inhibition in FM patients, decreasing their sensitivity to pain. Thus, exercise may benefit patients with FM via improving the functional capacity of the pain modulatory system

Team-Based Integrated Knowledge Translation for Enhancing Quality of Life in Long-term Care Settings: A Multi-method, Multi-sectoral Research Design

Multi-sectoral, interdisciplinary health research is increasingly recognizing integrated knowledge translation (iKT) as essential. It is characterized by diverse research partnerships, and iterative knowledge engagement, translation processes and democratized knowledge production. This paper reviews the methodological complexity and decision-making of a large iKT project called Seniors - Adding Life to Years (SALTY), designed to generate evidence to improve late life in long-term care (LTC) settings across Canada. We discuss our approach to iKT by reviewing iterative processes of team development and knowledge engagement within the LTC sector. We conclude with a brief discussion of the important opportunities, challenges, and implications these processes have for LTC research, and the sector more broadly

The thermal tolerance of photosynthetic tissues: a global systematic review and agenda for future research

Understanding plant thermal tolerance is fundamental to predicting impacts of extreme temperature events that are increasing in frequency and intensity across the globe. Extremes, not averages, drive species evolution, determine survival, and increased crop performance. To better prioritise agricultural and natural system research, it is crucial to evaluate how researchers are assessing the capacity of plants to tolerate extreme events. We conducted a systematic review to determine how plant thermal tolerance research is distributed across wild and domesticated plants, growth forms and biomes, and identify crucial knowledge gaps. Our review shows that most thermal tolerance research examines cold tolerance of cultivated species; ~5% of articles consider both heat and cold tolerance. Plants of extreme environments are understudied, and techniques widely applied in cultivated systems are largely unused in natural systems. Lastly, we find that lack of standardised methods and metrics compromises the potential for mechanistic insight. Our review provides an entry point for those new to the methods used in plant thermal tolerance research and bridges often disparate ecological and agricultural perspectives for the more experienced. We present a considered agenda of thermal tolerance research priorities to stimulate efficient, reliable, and repeatable research across the spectrum of plant thermal tolerance