Protective Gene Expression Changes Elicited by an Inherited Defect in Photoreceptor Structure

Inherited defects in retinal photoreceptor structure impair visual transduction, disrupt relationship with the retinal pigment epithelium (RPE), and compromise cell viability. A variety of progressive retinal degenerative diseases can result, and knowledge of disease etiology remains incomplete. To investigate pathogenic mechanisms in such instances, we have characterized rod photoreceptor and retinal gene expression changes in response to a defined insult to photoreceptor structure, using the retinal degeneration slow (rds) mouse model. Global gene expression profiling was performed on flow-sorted rds and wild-type rod photoreceptors immediately prior and subsequent to times at which OSs are normally elaborated. Dysregulated genes were identified via microarray hybridization, and selected candidates were validated using quantitative PCR analyses. Both the array and qPCR data revealed that gene expression changes were generally modest and dispersed amongst a variety of known functional networks. Although genes showing major (>5-fold) differential expression were identified in a few instances, nearly all displayed transient temporal profiles, returning to WT levels by postnatal day (P) 21. These observations suggest that major defects in photoreceptor cell structure may induce early homeostatic responses, which function in a protective manner to promote cell viability. We identified a single key gene, Egr1, that was dysregulated in a sustained fashion in rds rod photoreceptors and retina. Egr1 upregulation was associated with microglial activation and migration into the outer retina at times subsequent to the major peak of photoreceptor cell death. Interestingly, this response was accompanied by neurotrophic factor upregulation. We hypothesize that activation of Egr1 and neurotrophic factors may represent a protective immune mechanism which contributes to the characteristically slow retinal degeneration of the rds mouse model

Growth response to resistance exercise : influence of exercise device

The purpose of this study was to compare the growth response elicited by an acute bout of resistance exercise (RE) conducted on a traditional weight stack device (WS) and a flywheel device (FW). Eight recreationally trained males (25 ± 9 y, 77 ± 27 kg) performed 4 sets of 7 repetitions of bilateral knee extension on each exercise device separated by 7 days. Muscle biopsies were obtained from the vastus lateralis at rest and 4 hrs post-exercise to examine the expression of selected myogenic and proteolytic genes. RE increased (P < 0.05) mRNA expression of Myogenin (3.6 vs. 3.6 fold), and MyoD (2.2 vs. 2.0 fold) and decreased (P < 0.05) expression of Myostatin (1.4 vs. 1.5 fold) to a similar degree on both exercise devices. There was no change in the expression of Atrogin-1, MuRF-1 or MRF4 following RE on either device. The only device mediated difference in the expression of the selected genes was observed in Atrogin-1 which was lower following RE on the FW versus the WS device. The current data shows that in the initial hrs following RE, use of the FW is as effective as the traditional resistance training devices (WS) in promoting the induction of genes involved with muscle remodeling and growth.School of Physical Education, Sport, and Exercise ScienceThesis (Ph. D.

The influence of training status on ERK and AKT phosphorylation in human skeletal muscle

Exercise induces morphological and metabolic adaptations that are highly specific to the mode of exercise training. These specific phenotypical changes are due to an equally specific molecular response that may depend on the activation and coordination intramuscular signaling pathways. Just as metabolic and morphological changes are influenced by the mode of exercise training, the signaling pathways that mediate exercise adaptation may also be directly related to the training status of skeletal muscle. For example, pre-conditioned skeletal muscle may exhibit a specific intracellular signaling response to an acute bout of exercise that is dependent on past training history. Both Akt (protein kinase B) and extra-cellular signal-related kinase (ERK 1 /2) have been shown to be phosphorylated in response to an acute bout of resistance exercise in human skeletal muscle and have been suggested to mediate the adaptive response to exercise. The purpose of this investigation was to examine the response of Akt and ERKI/2 to an acute bout of resistance exercise in three groups with distinctly different exercise training backgrounds. Twenty one subjects performed 3 sets of 10 repetitions of knee extension exercise at 70% 1-RM. The subjects consisted of a resistance-trained group (RE) (n=7), endurance trained group (END) (n=7) and a sedentary group (SED) (n=7). Muscle biopsies were taken from the vastus lateralis muscle before, immediately after, and 10 min post-exercise and were analyzed for phosphorylation of Akt and ERK1/2. ERK1/2 phosphorylation increased 47%, and 54% from pre-exercise to immediately post-exercise in the SED and RE groups respectively (p < 0.05). ERK1/2 phosphorylation increased 95%, 196%, and 47% from pre-exercise to 10 min post-exercise in the SED, RE, and END groups, respectively. (p < 0.05). The magnitude of ERK1/2 phosphorylation 10 min post-exercise was different between each group and may be linked to the group's training status. (p < 0.05) Akt phosphorylation decreased 42% and 37% from pre-exercise to immediately post-exercise in the SED and END group, respectively (p < 0.05). There was a 40 % increase in Akt phosphorylation from immediate post-exercise to 10 min post-exercise in the END group. In conclusion, training status appears to influence the magnitude and time course of activation of both Akt and ERK1/2 in response to an acute bout of resistance exercise. The immediate response of both ERK1/2 and Akt may play a key role in the adaptive response of skeletal muscle ultimately resulting in metabolic and morphological changes that are dependent on the past training history of the individual.Thesis (M.S.)School of Physical Education, Sport, and Exercise Scienc

The influence of training status on ERK and AKT phosphorylation in human skeletal muscle

Exercise induces morphological and metabolic adaptations that are highly specific to the mode of exercise training. These specific phenotypical changes are due to an equally specific molecular response that may depend on the activation and coordination intramuscular signaling pathways. Just as metabolic and morphological changes are influenced by the mode of exercise training, the signaling pathways that mediate exercise adaptation may also be directly related to the training status of skeletal muscle. For example, pre-conditioned skeletal muscle may exhibit a specific intracellular signaling response to an acute bout of exercise that is dependent on past training history. Both Akt (protein kinase B) and extra-cellular signal-related kinase (ERK 1 /2) have been shown to be phosphorylated in response to an acute bout of resistance exercise in human skeletal muscle and have been suggested to mediate the adaptive response to exercise. The purpose of this investigation was to examine the response of Akt and ERKI/2 to an acute bout of resistance exercise in three groups with distinctly different exercise training backgrounds. Twenty one subjects performed 3 sets of 10 repetitions of knee extension exercise at 70% 1-RM. The subjects consisted of a resistance-trained group (RE) (n=7), endurance trained group (END) (n=7) and a sedentary group (SED) (n=7). Muscle biopsies were taken from the vastus lateralis muscle before, immediately after, and 10 min post-exercise and were analyzed for phosphorylation of Akt and ERK1/2. ERK1/2 phosphorylation increased 47%, and 54% from pre-exercise to immediately post-exercise in the SED and RE groups respectively (p < 0.05). ERK1/2 phosphorylation increased 95%, 196%, and 47% from pre-exercise to 10 min post-exercise in the SED, RE, and END groups, respectively. (p < 0.05). The magnitude of ERK1/2 phosphorylation 10 min post-exercise was different between each group and may be linked to the group's training status. (p < 0.05) Akt phosphorylation decreased 42% and 37% from pre-exercise to immediately post-exercise in the SED and END group, respectively (p < 0.05). There was a 40 % increase in Akt phosphorylation from immediate post-exercise to 10 min post-exercise in the END group. In conclusion, training status appears to influence the magnitude and time course of activation of both Akt and ERK1/2 in response to an acute bout of resistance exercise. The immediate response of both ERK1/2 and Akt may play a key role in the adaptive response of skeletal muscle ultimately resulting in metabolic and morphological changes that are dependent on the past training history of the individual.School of Physical Education, Sport, and Exercise ScienceThesis (M.S.

Effect of food form on postprandial plasma amino acid concentrations in older adults

To assess the effect of food form (FF) on postprandial (PP) plasma amino acid (AA) concentrations, ten older adults (five men and five women, age 72 (sem 2) years, BMI 26·0 (sem 0·9) kg/m2) consumed, on separate days, energy and macronutrient-matched test meal replacement products (MRP) (approximately 25 % of the subject's daily energy need; approximately 54 % carbohydrate, 21 % protein, 25 % fat) in beverage and solid form. Blood samples were taken during fasting and throughout the 4 h PP period; plasma AA concentrations were assessed using HPLC. Consumption of each MRP led to an increase in total AA, branched-chain AA (BCAA), essential AA (EAA), non-essential AA (NEAA) and leucine concentrations (4 h area under the curve, AUC) (time effect; P &lt; 0·05). The beverage MRP resulted in a greater initial (i.e. 30 min) and sustained (4 h AUC) increase in total AA, BCAA, EAA, NEAA and leucine concentrations compared with the solid MRP (each effect of FF; P &lt; 0·05). Although there was no effect of FF on PP insulin response, glucose concentration was greater 1 and 2 h after the solid MRP was consumed (FF × time interaction; P &lt; 0·05). For all PP time points combined, total AA concentration was positively associated with plasma insulin (r 0·25) and glucose (r 0·24) concentrations for the solid MRP but not for the beverage MRP. In conclusion, older adults can achieve higher plasma AA concentrations when a protein-containing MRP is ingested in beverage form. The implications of the higher AA availability on anabolic processes warrant investigation.</jats:p