Biomedical subjects

E G Noble

Publications and source records attributed to E G Noble.

36 records · Page 2Linked to original sources

PubMed1995

Stress proteins: the exercise response.

A class of proteins that undergoes preferential synthesis following a variety of stressors has been demonstrated to carry out important cellular functions under both stressed and nonstressed conditions. These so-called heat shock (HSP) or stress (SP) proteins have been termed "molecular chaperones" and play important roles in cellular transportation, assembly/degradation, and cell survival. This review provides a basic introduction to the function and regulation of these proteins. Emphasis is placed on members of the HSP 70 family of proteins (especially HSP 72) and their role in cellular protection, their pattern of distribution in skeletal muscle, and changes in their expression following exercise and exercise training.

Animals↗

PubMed1995

Activation of heat-shock transcription factor in rat heart after heat shock and exercise.

Stress-induced transcriptional regulation of the heat-shock proteins (HSP) is mediated by activation and binding of the heat-shock transcription factors (HSF) to the heat-shock element (HSE). Given the similarities between the stressors known to activate the HSF in cultured cells and the physiological stresses known to occur during exercise, HSF activation was examined in the hearts from exercising animals. Sprague-Dawley rats (5 rats/group) were run on a treadmill (24 m/min) for either 0, 20, 40, or 60 min or to exhaustion (102 +/- 7 min). Protein extracts were assessed for HSF activation by mobility-shift gels. Extracts from the hearts of nonrunning rats demonstrated no HSF activation, whereas HSF activation was detected in 80% of the hearts from animals that run for at least 40 min. These results demonstrate that treadmill running is capable of activating the HSF and increasing 70-kDa HSP mRNA in the rat myocardium.

Animals↗

PubMed1994

Shifts in type I fiber proportion in rat hindlimb muscle are accompanied by changes in HSP72 content.

Heat-shock protein 72 (HSP72), the inducible isoform of the HSP70 family, is constitutively expressed in rat hindlimb muscles in proportion to the content of type I muscle fibers. To determine whether this relationship was maintained after fiber transformation, male Sprague-Dawley rats were treated with 3,5,3'-triiodo-DL-thyronine (T3) for 40 days or underwent surgical removal of the left gastrocnemius muscle, after which the left plantaris muscle was allowed to hypertrophy for 30 days. Hypertrophied plantaris muscles exhibited an increased number of type I fibers, type I myosin heavy-chain (MHC) protein, and HSP72 content compared with contralateral muscles. Soleus muscles from rats administered T3 exhibited an increased number of type II fibers, citrate synthase activity, and decreased HSP72 content compared with soleus muscles from controls. These results indicate that the relationship between HSP72 content and type I muscle fiber-MHC composition is maintained when muscles undergo fiber transformation and substantiate that HSP72 content in rat skeletal muscle is not directly linked to a muscle's oxidative capacity.

Animals↗

PubMed1994

The effect of STZ-induced diabetes on serum triiodothyronine (T3) and thyroxine (T4) levels in the rat: a seven week time course.

This study examined the effect of a seven week period of diabetes on serum triiodothyronine (T3) and thyroxine (T4) levels in male Sprague-Dawley rats. Diabetes was induced by a sublingual injection of streptozotocin (80 mg/kg) in one-half of the animals (D) while the other half of the animals received a sham injection of 40mM citrate (pH 4.5) (C). Blood was sampled weekly via a cardiac puncture and serum T3 and T4 levels were determined by radioimmunoassay (Pharmacia) techniques. For the first two weeks after diabetes inducement T3 levels were significantly (p < or = .05) less in the D animals, after which time T3 levels did not differ significantly (p < or = .05) between the two groups. A significant (p < or = .05) decrease in serum T4 levels occurred by the first week of diabetes and was sustained through the seventh week. T3:T4 ratio was significantly (p < or = .05) higher in the diabetic animals at weeks 2 and 5. These findings suggest that the organism attempts to maintain levels of the more biologically active of the two thyroid hormones, T3, at the expense of circulating levels of serum T4 during prolonged states of STZ-induced diabetes.

Animals↗

PubMed1991

Inducible isoform of HSP70 is constitutively expressed in a muscle fiber type specific pattern.

The most prominent group of stress or heat-shock proteins (HSPs) has an Mr of approximately 70,000 and is collectively referred to as the HSP70 family. The extent of stress inducibility and subcellular location of the various HSP70 isoforms differ, but all appear to be involved with ATP-dependent stabilization or solubilization of proteins. One isoform, termed the inducible isoform of HSP70 (HSP72i), is normally absent in unstressed cells. In a previous study, we detected a protein corresponding in Mr and pI to HSP72i in unstressed rat muscle. Therefore, it was of interest to determine if this expression in unstressed muscle cells is general or confined to specific muscle fiber types. To answer this question we have employed various rat hindlimb muscles that differ in fiber type proportion from predominantly type I (soleus) to predominantly type IIB (white gastrocnemius). Proteins from muscle homogenates were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, blotted to a nylon membrane, probed with a monoclonal antibody for HSP72i, and visualized using an alkaline phosphatase-conjugated secondary antibody. Immunoblot analyses demonstrate the constitutive expression of HSP72i in rat muscles comprised primarily of type I muscle fibers (soleus), but not in muscles comprised primarily of type IIB fibers (white gastrocnemius). In muscles of mixed fiber type, HSP72i content is roughly proportional to the percentage of type I fibers. These results substantiate that unstressed rat muscles express the inducible HSP72 isoform and demonstrate that its constitutive expression is proportional to the type I muscle fiber composition.

Animals↗

PubMed1991

Shifts in rat plantaris motor unit characteristics with aging and compensatory overload.

Contractile characteristics of single motor units from plantaris muscles of young (6 mo), middle-aged (14 mo), and older (20 mo) rats were examined. Some of the muscles were subjected to a short-term (30 days) compensatory overload. After overload, the absolute increase in muscle weight was less for the 20-mo-old rats (38%) than the other groups (62%). However, when muscle weight per unit body weight was examined, the ratio was increased to a similar extent for all age groups. Aging was associated with an increase in slow (6 mo, 12.5%; 14 mo, 17.7%; 20 mo, 30.2%) and transitional (6 mo, 2.5%; 14 mo, 15.2%; 20 mo, 12.7%) motor unit proportions. This increase initially occurred at the expense of fast-fatigable motor units (6 mo, 36.3%; 14 mo, 13.9%; 20 mo, 20.7%) and then fast-intermediate units (6 mo, 40%; 14 mo, 39.2%; 20 mo, 26.7%). In addition, the maximal tension of individual motor units tended to increase with age. In younger rats compensatory overload produced changes in the motor unit profile similar to those that occurred with aging. In contrast, overload of the plantaris from 20-mo-old rats resulted in an increase in the force contribution from fast motor units. These results demonstrate that aging is accompanied by a gradual reorganization of the skeletal muscle motor unit pool, such that there is a loss of fast motor units and an increase in the proportion of slow motor units. While compensatory overload initially appears to mimic the aging effect, in older animals it may delay or reverse some of the age-related changes.

Adaptation, Physiological↗

PubMed1990

Exercising mammals synthesize stress proteins.

Spleen cells, peripheral lymphocytes, and soleus muscles were removed from male Sprague-Dawley rats that had been run on a treadmill (24 m/min) for either 20, 40, or 60 min or to exhaustion (86 +/- 41 min) and were labeled in vitro with [35S]methionine at 37 degrees C. Similar tissues from nonrunning control rats were labeled in vitro at either 37 or 43 degrees C (heat shock). Fluorographic analyses of one- and two-dimensional polyacrylamide gel electrophoretic separations of the proteins from cells and tissues of exercised rats demonstrate the new or enhanced synthesis of proteins of approximately 65, 72, 90, and 100 kDa. Although synthesis of these proteins is low or not detectable in tissues from control rats labeled at 37 degrees C, they are prominent products of similar tissues labeled under heat-shock conditions (43 degrees C) and, in fact, correspond in Mr and pI with the so-called heat-shock proteins. These results suggest that exercise is a sufficient stimulus to induce or enhance the synthesis of heat shock and/or stress proteins in mammalian cells and tissues.

Animals↗

PubMed1989

Appearance of "transitional" motor units in overloaded rat skeletal muscle.

The contractile characteristics of single motor units, isolated from rat plantaris muscles subjected to short-term (30 days) compensatory overload, were assessed to determine whether motor units in transition could be detected. In the control plantaris 88% of the motor units were classified as fast. After overload, a large decline (26.5%) in the proportion of typical fast motor units was noted. The estimated contribution of fast fatigable units to whole muscle tetanic tension (Po 200) also declined (from 55 to 25%), whereas that of fast intermediate motor units increased (from 33 to 55%). In the overloaded plantaris, motor units that exhibited unusual "sag" and contraction time characteristics were detected. These motor units, which could be further subdivided into two distinct types by a variety of indexes, exhibited characteristics intermediate to fast and slow units and therefore were termed "transitional." Transitional units accounted for 12% of the estimated whole muscle Po200 after overload. These experiments characterize novel classifications of motor units undergoing transformation and further detail the motor unit shift that accompanies compensatory overload.

Analysis of Variance↗

PubMed1989

Effect of dietary manipulation on a high intensity performance test.

The effects of dietary manipulation (low- or high-carbohydrate) on performance of a short-duration exercise were studied with endurance- and intermittent-trained athletes. Eight subjects performed a depletion drill of 10 one minute workbouts at 7 W/kg and 85 rpm on a cycle ergometer. The subjects followed a dietary regimen of three days on a low-carbohydrate diet followed by three days on a high-carbohydrate diet. Muscle biopsy samples were taken immediately prior to and immediately after the testing sessions. Dietary manipulation did not affect resting muscle glycogen levels. However, subjects accustomed to continuous training regimens used less glycogen, produced less muscle lactate and exercised longer than subjects accustomed to intermittent training programs. These biochemical changes appeared to be related to the fibre type distribution and the training background of the athletes.

Adult↗

PubMed1988

Simple and complex carbohydrate-rich diets and muscle glycogen content of marathon runners.

The effects of simple-carbohydrate (CHO)- and complex-CHO-rich diets on skeletal muscle glycogen content were compared. Twenty male marathon runners were divided into four equal groups with reference to dietary consumption: depletion/simple, depletion/complex, nondepletion/simple, and nondepletion/complex. Subjects consumed either a low-CHO (15% energy [E] intake), or a mixed diet (50% CHO) for 3 days, immediately followed by a high-CHO diet (70% E intake) predominant in either simple-CHO or in complex-CHO (85% of total CHO intake) for another 3 days. Skeletal muscle biopsies and venous blood samples were obtained one day prior to the start of the low-CHO diet or mixed diet (PRE), and then again one day after the completion of the high-CHO diet (POST). The samples were analysed for skeletal muscle glycogen, serum free fatty acids (FFA), insulin, and lactate and blood glucose. Skeletal muscle glycogen content increased significantly (p less than 0.05) only in the nondepletion/simple group. When groups were combined, according to the type of CHO ingested and/or utilization of a depletion diet, significant increases were observed in glycogen content. Serum FFA decreased significantly (p less than 0.05) for the nondepletion/complex group only, while serum insulin, blood glucose, and serum lactate were not altered. It is concluded that significant increases in skeletal muscle glycogen content can be achieved with a diet high in simple-CHO or complex-CHO, with or without initial consumption of a low-CHO diet.

Adult↗

PubMed1988

Lipoprotein lipase activity in skeletal muscle and adipose tissue of marathon runners after simple and complex carbohydrate-rich diets.

A comparison of the influence of simple and complex carbohydrate (CHO) consumption on adipose tissue- and skeletal muscle-lipoprotein lipase activity (AT-LPLA, SM-LPLA) was examined. Twenty male marathon runners were divided into two equal dietary groups: simple-CHO and complex-CHO. Half of the subjects in each group consumed either a low-CHO (15% energy [E] intake), or a mixed diet (50% CHO) for 3 days. Immediately following this dietary period, the subjects consumed a CHO-rich diet (70% E intake) predominant in simple-CHO or in complex-CHO for an additional 3 days. Thereafter, all subjects returned to a normal mixed diet. Skeletal muscle biopsies, adipose tissue aspirations, and venous blood samples were obtained prior to dietary manipulation (PRE), upon completion of the 6 day diet (POST I), and 2 weeks after returning to a normal diet (POST II). The samples were analysed for AT-LPLA, SM-LPLA, serum insulin, and free fatty acids (FFA), and blood glucose, and lactate. SM-LPLA fell 71% from PRE values of 0.39 +/- 0.30 mu mol.g-1.h-1 to POST I values of 0.11 +/- 0.09 mu mol.g-1.h-1 (means +/- SD) (p less than 0.05), after a complex-CHO diet. However, the simple-CHO diet did not alter SM-LPLA. AT-LPLA similarly decreased (p less than 0.05) after the complex-CHO diet, and no significant decrease was noted after the simple-CHO diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

PubMed1985

Influence of training on skeletal muscle enzymatic adaptations in normal and diabetic rats.

Muscle homogenates representing slow-twitch oxidative, fast-twitch oxidative-glycolytic, fast-twitch glycolytic, and mixed fiber types were prepared from normal, diabetic, and insulin-treated diabetic rats. Diabetes was induced by injection of 80 mg . kg-1 of streptozotocin. The activities of citrate synthase, succinate dehydrogenase, and 3-hydroxyacyl-CoA dehydrogenase were employed as markers of oxidative potential, whereas phosphorylase, hexokinase, and phosphofructokinase activities were used as an indication of glycolytic capacity. Diabetes was associated with a general decrement in the activity of oxidative marker enzymes for all fiber types except the fast-twitch glycolytic fiber. In contrast, the fast-twitch glycolytic fibers demonstrated the greatest decline in glycolytic enzymatic activity. Insulin-treated animals, either trained or untrained, exhibited enzyme activities similar to their normal counterparts. Exercise training of diabetic rats mimicked the effect of insulin treatment and caused a near normalization of the activity of the marker enzymes. These findings suggest that the enzymatic potential of all skeletal muscle fiber types of diabetic rats may be normalized by exercise training even in the absence of significant amounts of insulin.

Adaptation, Physiological↗

PubMed1984

Protein synthesis in compensatory hypertrophy of rat plantaris.

Protein synthesis in rat plantaris muscle undergoing surgically induced hypertrophy was studied using a perfused hindquarter preparation. The tissue mass of the hypertrophied muscle increased 11, 33, 33, and 104% at 2, 5, 15, and 50 days postsurgery. Total tissue protein synthesis was unchanged during the early phase but was significantly elevated after 15 and 50 days of work overload. Myosin synthesis was also significantly elevated after 15 and 50 days of hypertrophic growth. Increases in muscle protein content (milligrams per muscle) for each protein fraction examined were temporally in step with the altered synthetic rates. The shift in muscle fibre-type profile from approximately 10% alkaline-labile fibres in the control muscle to about 25% alkaline-labile fibres in the hypertrophied muscle also followed a similar time course. These data suggest that during compensatory hypertrophy, enhanced protein synthesis may be the dominant mechanism for the massive accumulation of muscle protein. However, its contribution to muscle growth does not become evident until about 15 days after the initial growth stimulus.

Animals↗

PubMed1984

Glycogen repletion in different skeletal muscles from diabetic rats.

It was hypothesized that chronically untreated streptozotocin-diabetic rats may compensate for the detrimental effect of insulin deficiency on glycogen restoration following muscular work. Glycogen concentration ([GLY]) was reduced by in situ stimulation of the sciatic nerve of anesthetized normal (N) and diabetic (D) Sprague-Dawley albino rats. Glycogen repletion occurred most rapidly within 30 min after stimulation. By 2 h all N muscles returned to basal [GLY]. D muscles repleted glycogen at a rate 45-75% of normal and not all of the D muscle returned to basal [GLY] by 8 h poststimulation. Neither the partial reduction in diabetic hyperglycemia by using phlorizin nor the acute further lowering of diabetic hypoinsulinemia by using insulin antibody affected glycogen restoration in D muscles. Acute insulin replenishment resulted in restoration of normal [GLY] in D muscles within 2 h poststimulation. These findings are not consistent with the proposed hypothesis and indicate insulin is necessary to have normal rates of glycogen restoration following muscular activity.

Animals↗

PubMed1983

Myosin transformation in hypertrophied rat muscle.

Chronic hypertrophy (X = 88%) of the fast-twitch rat plantaris muscle was induced by surgical ablation of the synergistic gastrocnemius. Alterations in the catalytic activity and the light chain composition of myosin extracted from the hypertrophied plantaris muscle were examined. The hypertrophied muscle exhibited a decreased Ca2+-activated myosin ATPase activity and an increase in the content of LCS1 and LCS2 light chains when compared to its contralateral control. These changes, which occur in the absence of a direct manipulation of the muscle's innervation, suggest that the histochemically observed increase in the percent of alkaline labile fibres found in hypertrophied muscle are the result of the expression of a different myosin phenotype.

Animals↗

PubMed1982

Effects of streptozotocin diabetes, insulin treatment, and training on the diaphragm.

The adaptive capability of the diaphragm, the only skeletal muscle considered a vital organ, has received little investigative attention compared with the limb muscles. Since it is chronically active, we asked whether it will adapt to exercise training and if so to what extent. Metabolic adaptations of the diaphragm to exercise training were studied under three conditions: normal, streptozotocin-diabetic, and diabetic receiving insulin treatment. The activities of hexokinase (HK), phosphorylase, and phosphofructokinase (PFK) in the diaphragm of sedentary diabetic Sprague-Dawley albino rats were 22-36% lower than in normal animals. Insulin treatment returned PFK and HK to normal and above normal, respectively. Tricarboxylic acid cycle marker enzymes were not affected by the diabetic condition or insulin treatment. beta-Oxidation enzyme 3-hydroxyacyl-CoA dehydrogenase (HADH) was 60% higher than normal in the diabetic diaphragm and returned to normal with insulin treatment. Training resulted in increases in the glycolytic and aerobic capacities of all groups. The aerobic changes were similar to those of limb muscles. HADH activity was increased in the normal and diabetic insulin-treated trained groups, but because of its already high activity in the diabetic diaphragm, it did not require an adaptation.

Animals↗

PubMed1982

Exercise-induced glycogenolysis in sympathectomized rats.

The role of the adrenergic system in regulating glycogenolysis during exercise was studied in rats. Alterations in the adrenergic system were produced by injections of 6-hydroxydopamine (6-OHD), surgical removal of the adrenal medulla (ADMX), or the combination of ADMX and 6-OHD injection. Exercise was treadmill running at 22 m/min for 60 min. Colonic temperature averaged 2.8 degrees C higher in the exercised than control rats. Exercise reduced the glycogen of the liver and skeletal muscles of all groups. The glycogen concentrations of the soleus and red portion of the gastrocnemius muscles of the ADMX and ADMX-6-OHD groups were about 3.8 and 2.5 times higher after exercise than those of the normal-exercised rats. Glycogen depletion of the white portion of the gastrocnemius muscle was similar for all exercised groups. 6-OHD treatment depleted the catecholamines of the myocardium. These results demonstrate that glycogen depletion during exercise occurs in rats devoid of adrenergic control. However, differences between types of skeletal muscle suggest that factors other than the adrenergic system may be involved in controlling glycogen metabolism during exercise.

Adrenal Medulla↗

PubMed1981

Lipolysis and cAMP accumulation in adipocytes in response to physical training.

Adenylate cyclase activity is lower in membrane preparations of fat cell homogenates from exercise-trained compared with sedentary rats (J. Appl. Physiol.: Respirat. Environ, Exercise Physiol. 42: 884-888, 1977). In the present investigations lipolysis and cyclic adenosine 3':5'-monophosphate (cAMP) accumulation were measured in isolated parametrial fat cells prepared from sedentary and trained rats. The purpose of these investigations was to determine whether the normal catecholamine-induced increases in cAMP accumulation is affected in isolated adipocytes from endurance-trained rats. The increases in cAMP accumulation in response to isoproterenol (0.01-10 microM) was reduced in fat cells isolated from trained rats. However, glycerol release in response to the same hormonal challenge was greater in these adipocytes. cAMP phosphodiesterase activity measured at 0.125 and 1.025 microM cAMP was greater in the particulate fraction of fat cell homogenates obtained from trained rats as compared with their sedentary counterparts. Hormone-sensitive lipase activity was reduced in crude fat pad homogenate preparations from trained rats if the animals were killed at rest. However, if the animals were run to exhaustion immediately prior to being killed, there were no differences in the hormone-sensitive lipase activity between preparations from trained and nontrained rats. These data indicate that, although cAMP accumulation by isolated fat cells in response to isoproterenol is markedly lower in trained rats, lipolysis and hormone-sensitive lipase activation is not reduced.

3',5'-Cyclic-AMP Phosphodiesterases↗