scholarly journals Muscle adaptations to hindlimb suspension in mature and old Fischer 344 rats

1997 ◽  
Vol 82 (6) ◽  
pp. 1875-1881 ◽  
Author(s):  
Craig S. Stump ◽  
Charles M. Tipton ◽  
Erik J. Henriksen
Keyword(s):  
Cardiac Muscle ◽  
Old Age ◽  
Glucose Transporter ◽  
Citrate Synthase ◽  
Hindlimb Suspension ◽  
Fischer 344 Rats ◽  
Fischer 344 ◽  
Glut 4 ◽  
Hindlimb Muscles ◽  
Old Rats

Stump, Craig S., Charles M. Tipton, and Erik J. Henriksen.Muscle adaptations to hindlimb suspension in mature and old Fischer 344 rats. J. Appl. Physiol.82(6): 1875–1881, 1997.—We examined skeletal and cardiac muscle responses of mature (8 mo) and old (23 mo) male Fischer 344 rats to 14 days of hindlimb suspension. Hexokinase (HK) and citrate synthase (CS) activities and GLUT-4 glucose transporter protein level, which are coregulated in many instances of altered neuromuscular activity, were analyzed in soleus (Sol), plantaris (Pl), tibialis anterior (TA), extensor digitorum longus (EDL), and left ventricle. Protein content was significantly ( P < 0.05) lower in all four hindlimb muscles after suspension compared with controls in both mature (21–44%) and old (17–43%) rats. Old rats exhibited significantly lower CS activities than mature rats for the Sol, Pl, and TA. HK activities were significantly lower in the old rats for the Pl (19%) and TA (33%), and GLUT-4 levels were lower in the old rats for the TA (38%) and EDL (24%) compared with the mature rats. Old age was also associated with a decrease in CS activity (12%) and an increase in HK activity (14%) in cardiac muscle. CS activities were lower in the Sol (20%) and EDL (18%) muscles from mature suspended rats and in the Sol (25%), Pl (27%), and EDL (25%) muscles from old suspended rats compared with corresponding controls. However, suspension was associated with significantly higher HK activities for all four hindlimb muscles examined, in both old (16–57%) and mature (10–43%) rats, and higher GLUT-4 concentrations in the TA muscles of the old rats (68%) but not the mature rats. These results indicate that old age is associated with decreased CS and HK activities and GLUT-4 protein concentration for several rat hindlimb muscles, and these variables are not coregulated during suspension. Finally, old rat skeletal muscle appears to respond to suspension to a similar or greater degree than mature rat muscle responds.

Glucose transporter content and enzymes of metabolism in nerve-repair grafted muscle of aging Fischer 344 rats

1997 ◽  
Vol 83 (5) ◽  
pp. 1623-1629 ◽  
Author(s):  
Lisa Larkin ◽  
Eric R. Leiendecker ◽  
Mark Supiano ◽  
Jeffrey Halter
Keyword(s):  
Glucose Transporter ◽  
Citrate Synthase ◽  
Nerve Repair ◽  
Medial Gastrocnemius ◽  
Fischer 344 Rats ◽  
Glut 1 ◽  
Fischer 344 ◽  
Glut 4 ◽  
Phosphofructokinase Activity ◽  
And Control

Larkin, Lisa, Eric R. Leiendecker, Mark Supiano, and Jeffrey Halter. Glucose transporter content and enzymes of metabolism in nerve-repair grafted muscle of aging Fischer 344 rats. J. Appl. Physiol. 83(5): 1623–1629, 1997.—Aging and grafting are associated with decreased ability of muscle to sustain power, likely reflecting diminished fuel availability. To assess mechanisms that may contribute to availability of glucose, we studied GLUT-1 and GLUT-4 protein as well as mRNA contents and enzymes of glucose metabolism in grafted and control medial gastrocnemius (MG) muscles of 6-, 12-, and 24-mo-old male Fischer 344 rats. There was no effect of age or grafting on MG GLUT-4 content. There was both an age- and graft-associated increase in GLUT-1 content ( P = 0.0044 and 0.0063, respectively). There was no effect of aging or grafting on hexokinase and phosphofructokinase activity or on protein and glycogen content. Muscle mass and citrate synthase activity were significantly diminished with grafting. Citrate synthase activity was significantly greater in the 12-mo-old compared with the 6- and 24-mo-old animals. Grafting in combination with aging had no impact on any of the parameters measured. We conclude that diminished glucose transporter expression cannot explain the decreased ability of aged muscle to sustain power. In addition, we conclude that the diminished ability of the grafted MG muscle to sustain power may be explained, in part, by a decrease in energy available from oxidative metabolism.

Exercise training increases GLUT-4 protein concentration in previously sedentary middle-aged men

1993 ◽  
Vol 264 (6) ◽  
pp. E896-E901 ◽  
Author(s):  
J. A. Houmard ◽  
M. H. Shinebarger ◽  
P. L. Dolan ◽  
N. Leggett-Frazier ◽  
R. K. Bruner ◽  
...  
Keyword(s):  
Exercise Training ◽  
Protein Concentration ◽  
Glucose Transporter ◽  
Citrate Synthase ◽  
Sensitivity Index ◽  
Insulin Sensitivity Index ◽  
Middle Aged ◽  
Lateral Gastrocnemius ◽  
Transporter Protein ◽  
Glut 4

The purpose of this study was to determine if 14 wk of exercise training would increase insulin-sensitive glucose transporter protein (GLUT-4) concentration in skeletal muscle of previously sedentary middle-aged men (47.2 +/- 1.3 yr; n = 13). Muscle samples (lateral gastrocnemius) and insulin action [insulin sensitivity index (ISI), minimal model] were obtained in the sedentary condition and 48 h after the final training bout. GLUT-4 protein concentration increased (P < 0.001, 2,629 +/- 331 to 4,140 +/- 391 absorbance units/100 micrograms protein) with exercise training by 1.8-fold. ISI increased by twofold (P < 0.05, 2.1 +/- 0.5 to 3.4 +/- 0.7 SI x 10(5) min/pM) with training. The percentage of GLUT-4 rich type IIa muscle fibers increased by approximately 10% (P < 0.01), which may have contributed to the elevation in transporter protein. GLUT-4 concentration and citrate synthase activity (1.7-fold, P < 0.001) also increased by similar increments. These findings indicate that GLUT-4 protein concentration is elevated in middle-aged individuals with exercise training.

Glucose transporters and glucose transport in skeletal muscles of 1- to 25-mo-old rats

1993 ◽  
Vol 264 (3) ◽  
pp. E319-E327 ◽  
Author(s):  
E. A. Gulve ◽  
E. J. Henriksen ◽  
K. J. Rodnick ◽  
J. H. Youn ◽  
J. O. Holloszy
Keyword(s):  
Glucose Transport ◽  
Skeletal Muscles ◽  
Glucose Transporter ◽  
Contractile Activity ◽  
Transport Activity ◽  
Glut 4 ◽  
Flexor Digitorum Brevis ◽  
Old Rats ◽  
Growth And Aging ◽  
Flexor Digitorum

It is widely thought that aging results in development of insulin resistance in skeletal muscle. In this study, we examined the effects of growth and aging on the concentration of the GLUT-4 glucose transporter and on glucose transport activity in skeletal muscles of female Long-Evans rats. Relative amounts of immunoreactive GLUT-4 protein were measured in muscle homogenates of 1-, 10-, and 25-mo-old rats by immunoblotting with a polyclonal antibody directed against GLUT-4. In the epitrochlearis, plantaris, and the red and white regions of the quadriceps muscles, GLUT-4 immunoreactivity decreased by 14-33% between 1 and 10 mo of age and thereafter remained constant. In flexor digitorum brevis (FDB) and soleus muscles, GLUT-4 concentration was similar at all three ages studied. Glucose transport activity was assessed in epitrochlearis and FDB muscles by incubation with 2-deoxyglucose under the following conditions: basal, submaximal insulin, and either maximal insulin or maximal insulin combined with contractile activity. Glucose transport in the epitrochlearis muscle decreased by approximately 60% between 1 and 4 mo of age and then did not decline further between 4 and 25 mo of age. Transport activity in the FDB assessed with a maximally effective insulin concentration decreased only slightly (< 20%) between 1 and 7 mo of age. Aging, i.e., the transition from young adulthood to old age, was not associated with a decrease in glucose transport activity in either the epitrochlearis or the FDB.(ABSTRACT TRUNCATED AT 250 WORDS)

Overexpression of PKC-βI and -δ contributes to higher PKC activity in the proximal tubules of old Fischer 344 rats

2003 ◽  
Vol 285 (6) ◽  
pp. F1100-F1107 ◽  
Author(s):  
Mohammad Asghar ◽  
Tahir Hussain ◽  
Mustafa F. Lokhandwala
Keyword(s):  
Skf 38393 ◽  
Proximal Tubules ◽  
Fischer 344 Rats ◽  
Adult Rats ◽  
Altered Expression ◽  
Fischer 344 ◽  
Pkc Isoforms ◽  
Diuretic Response ◽  
Old Rats ◽  
Pkc Ζ

Previously, we reported that natriuretic and diuretic response to dopamine is diminished in old Fischer 344 rats, which is due to higher basal protein kinase C (PKC) activity and hyperphosphorylation of Na-K-ATPase in the proximal tubules (PTs) of old rats. The present study was conducted to determine whether higher PKC activity could be due to altered expression of some of the PKC isoforms in the superficial cortex (rich in PTs) of old rats. Fluorimetric measurement showed almost twofold increase in the PKC activities in homogenates and membranes of old (24 mo) compared with adult (6 mo) rats. Interestingly, in the basal state PKC-βI was overexpressed in the membranes, whereas PKC-δ expression was increased in the cytosol of old compared with adult rats. Treatment of the cortical slices with either SKF-38393, a D1-like agonist, or PDBu, a direct activator of PKC, caused translocation of PKC-βI from cytosol to membranes in adult but not in old rats. Both of these drugs caused translocation of PKC-δ from membranes to cytosol in adult but not in old rats. These drugs had no effect on translocation of PKC-ζ in both adult and old rats. Both PKC-βI and -δ coimmunoprecipiated with α1-subunit of Na-K-ATPase in adult and old rats. These observations suggest that both SKF-38393 and PDBu differentially regulate PKC-βI and -δ in adult but not in old rats. Also, PKC-βI and -δ seem to interact with Na-K-ATPase in these animals. The overexpression of both PKC-βI and -δ in old rats could be responsible for a higher basal PKC activity, which causes the hyperphosphorylation of Na-K-ATPase and contributes to the diminished inhibition of Na-K-ATPase activity by dopamine in old rats.

Role of glucose transport in glycogen supercompensation in reweighted rat skeletal muscle

1996 ◽  
Vol 80 (5) ◽  
pp. 1540-1546 ◽  
Author(s):  
E. J. Henriksen ◽  
C. S. Stump ◽  
T. H. Trinh ◽  
S. D. Beaty
Keyword(s):  
Glucose Transport ◽  
Citrate Synthase ◽  
Specific Activity ◽  
Glycogen Synthase ◽  
Average Rate ◽  
Weight Bearing ◽  
Hindlimb Suspension ◽  
Transport Activity ◽  
Glut 4 ◽  
Insulin Dependent

Hindlimb weight bearing after a 3-day period of hindlimb suspension (reweighting) of juvenile rats results in a marked transient elevation in soleus glycogen concentration that cannot be explained on the basis of the activities of glycogen synthase and phosphorylase. We have hypothesized that enhanced glucose transport activity could underlie this response. We directly tested this hypothesis by assessing the response of insulin-dependent and insulin-independent glucose transport activity (in vitro 2-[1,2-3H]deoxy-D-glucose uptake) as well as glucose transporter (GLUT-4) protein levels during a 48-h reweighting period. After a net glycogen loss (from 29 +/- 2 to 16 +/- 1 nmol/mg muscle; P < 0.05) during the first 2 h of reweighting, glycogen accumulated at an average rate of 1.4 nmol.mg-1.h-1 up to 18 h, reaching an apex of 38 +/- 1 nmol/mg. During this same reweighting period, insulin-independent, but not insulin-dependent, glucose transport activity was significantly enhanced (P < 0.05 vs. weight-bearing control values) and was associated with an elevated level of GLUT-4 protein and the specific activity of total hexokinase. The specific activity of citrate synthase was also increased. By 24 h of reweighting, although insulin-independent glucose transport activity and GLUT-4 protein remained elevated, glycogen accumulation had ceased, likely due to enhanced phosphorylase activity at this time point. These results are consistent with the interpretation that the glycogen supercompensation seen during reweighting of the rat soleus may be regulated in part by an enhanced glucose flux arising from an increase in insulin-independent glucose transport activity and hexokinase activity.

scholarly journals Aging and arteriosclerosis. I. Development of myointimal hyperplasia after endothelial injury.

1986 ◽  
Vol 164 (4) ◽  
pp. 1171-1178 ◽  
Author(s):  
R J Hariri ◽  
D R Alonso ◽  
D P Hajjar ◽  
D Coletti ◽  
M E Weksler
Keyword(s):  
Vascular Injury ◽  
Experimental Models ◽  
Endothelial Injury ◽  
Vascular Lesions ◽  
Fischer 344 Rats ◽  
Cell Nuclei ◽  
Fischer 344 ◽  
Endothelial Denudation ◽  
Old Rats ◽  
Intimal Thickness

Old Fischer 344 rats are more susceptible to vascular lesions after arterial endothelial injury than are young animals. Thus, 20-26-mo-old Fischer 344 rats developed greater and more persistent intimal proliferative lesions than did 2-5-mo-old rats after aortic endothelial denudation. 3 d after deendothelialization, intimal thickness was increased two-fold in both old and young animals. However, 14 d after endothelial injury, intimal thickness had increased nearly five times in old animals, but had regressed to normal in young animals. Intimal thickness of young aortic grafts transplanted into young recipients did not differ significantly from adjacent host aorta or autotransplanted aortic segments 6 wk after surgery. In contrast, intimal thickness of old grafts transplanted into young recipients was eight times greater than adjacent young host aorta 6 wk after surgery. The density of cell nuclei in the intima of old grafts was also much greater than that in young grafts. Thus, in two experimental models of vascular injury, old rats have consistently had greater myointimal hyperplasia than young rats. The increased proliferative response of aortic smooth muscle cells after vascular injury of old animals may contribute to the increased prevalence of vascular disease with age.

NAD(P)H oxidase-generated superoxide anion accounts for reduced control of myocardial O2 consumption by NO in old Fischer 344 rats

2003 ◽  
Vol 285 (3) ◽  
pp. H1015-H1022 ◽  
Author(s):  
Alexandra Adler ◽  
Eric Messina ◽  
Ben Sherman ◽  
Zipping Wang ◽  
Harer Huang ◽  
...  
Keyword(s):  
Oxidant Stress ◽  
Heart Weight ◽  
Fischer 344 Rats ◽  
No Donor ◽  
Fischer 344 ◽  
Old Rats ◽  
Fischer Rats ◽  
Enos Protein

We investigated the role of nitric oxide (NO) in the control of myocardial O2 consumption in Fischer 344 rats. In Fischer rats at 4, 14, and 23 mo of age, we examined cardiac function using echocardiography, the regulation of cardiac O2 consumption in vitro, endothelial NO synthase (eNOS) protein levels, and potential mechanisms that regulate superoxide. Aging was associated with a reduced ejection fraction [from 75 ± 2%at4moto66 ± 3% ( P < 0.05) at 23 mo] and an increased cardiac diastolic volume [from 0.60 ± 0.04 to 1.00 ± 0.10 ml ( P < 0.01)] and heart weight (from 0.70 ± 0.02 to 0.90 ± 0.02 g). The NO-mediated control of cardiac O2 consumption by bradykinin or enalaprilat was not different between 4 mo (36 ± 2 or 34 ± 3%) and 14 mo (29 ± 1 or 25 ± 3%) but markedly ( P < 0.05) reduced in 23-mo-old Fischer rats (15 ± 3 or 7 ± 2%). The response to the NO donor S-nitroso- N-acetyl penicillamine was not different across groups (35%, 35%, and 44%). Interestingly, the eNOS protein level was not different at 4, 14, and 23 mo. The addition of tempol (1 mmol/l) to the tissue bath eliminated the depression in the control of cardiac O2 consumption by bradykinin (25 ± 3%) or enalaprilat (28 ± 3%) in 23-mo-old Fischer rats. We next examined the levels of enzymes involved in the production and breakdown of superoxide. The expression of Mn SOD, Cu/Zn SOD, extracellular SOD, and p67phox, however, did not differ between 4- and 23-mo-old rats. Importantly, there was a marked increase in gp91phox, and apocynin restored the defect in NO-dependent control of cardiac O2 consumption at 23 mo to that seen in 4-mo-old rats, identifying the role of NADPH oxidase. Thus increased biological activity of superoxide and not decreases in the enzyme that produces NO are responsible for the altered control of cardiac O2 consumption by NO in 23-mo-old Fischer rats. Increased oxidant stress in aging, by decreasing NO bioavailability, may contribute not only to changes in myocardial function but also to altered regulation of vascular tone and the progression of cardiac or vascular disease.

Age-related immunosenescence in Fischer 344 rats: influence of exercise training

1992 ◽  
Vol 73 (5) ◽  
pp. 1932-1938 ◽  
Author(s):  
I. Nasrullah ◽  
R. S. Mazzeo
Keyword(s):  
Endurance Training ◽  
Interleukin 2 ◽  
Cytolytic Activity ◽  
Treadmill Running ◽  
Target Cells ◽  
Fischer 344 Rats ◽  
Middle Aged ◽  
Fischer 344 ◽  
Age Related ◽  
Old Rats

The present investigation examined the extent to which 15 wk of endurance training could influence immune function in young, middle-aged, and older animals. Forty-eight male Fischer 344 rats were divided into trained and untrained groups. Training consisted of treadmill running at 75% maximal running capacity for 1 h/day, 5 days/wk, for 15 wk. Animals were killed at 8, 17, and 27 mo, at which time splenocytes were isolated. The capacity for lymphocyte proliferation in response to mitogen (concanavalin A, ConA), interleukin-2 (IL-2) production, and cytolytic activity against YAC-1 target cells was determined. ConA-induced proliferation declined significantly with age. Training suppressed the proliferative response in the young (-41%) and middle-aged animals (-27%) compared with the age-matched controls; however, training improved this response (+58%) in the older group. IL-2 production followed a pattern similar to that for mitogen-induced proliferation, such that production declined with age and was reduced with training in young and middle-aged animals but was significantly more improved in the older animals than in age-matched controls. The ability to lyse target cells, measured as percent cytotoxicity, declined steadily with advancing age at all effector-to-target cell ratios tested: 52, 14, and -16% for 8-, 17-, and 27-mo-old rats, respectively. It was concluded that the capacity for ConA-induced splenocyte proliferation, IL-2 production, and cytolytic activity declines significantly with advancing age. Furthermore, 15 wk of endurance training suppressed proliferation and IL-2 production in young animals but improved these responses in older animals. Training had no effect on cytolytic activity.

Effect of age on induction of hepatic phosphoenolpyruvate carboxykinase by fasting

1994 ◽  
Vol 267 (2) ◽  
pp. G195-G200 ◽  
Author(s):  
H. Van Remmen ◽  
W. F. Ward
Keyword(s):  
G Protein ◽  
Time Course ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Age Groups ◽  
Fischer 344 Rats ◽  
Fischer 344 ◽  
Fasting And Refeeding ◽  
Old Rats ◽  
Rate Limiting ◽  
Effect Of Age

This study examines the effect of age on the induction of the rate-limiting enzyme in gluconeogenesis, phosphoenolpyruvate carboxykinase (PEPCK), in response to fasting and refeeding in male Fischer 344 rats aged 3-18 mo. The rats were fasted for 30 h to increase the activity of PEPCK and subsequently were refed for 24 h to lower activity toward basal levels. PEPCK activity increased 2.2-fold in the 3-mo-old rats and 2.3-fold in the 18-mo-old rats during the 30-h fast. Therefore PEPCK induction during the 30-h fast was not altered with age. Similarly, refeeding resulted in a significant decrease in PEPCK activity at all ages. After the 24-h refeeding period, the rats were fasted a second time, and the time course of induction from the basal refed level was measured. In the young rats (6 mo), the activity of PEPCK increased rapidly from 18.12 +/- 1.61 to 42.66 +/- 5.94 U/g protein (P < 0.01) within 8 h of fasting. However, in the 18-mo-old rats, the initiation of the induction of PEPCK activity was delayed, and, after 12 h, PEPCK activity had increased from 17.34 +/- 1.34 to only 32.50 +/- 3.21 U/g protein (P < 0.01). Furthermore, the rate of induction appears to be decreased in the older animals. The activity after 24 h of fasting was equivalent in all four age groups (ranging from 44.72 +/- 5.38 at 3 mo to 40.18 +/- 5.42 U/g protein at 18 mo).(ABSTRACT TRUNCATED AT 250 WORDS)

An age-related difference in hyperoxia lethality: role of lung antioxidant defense mechanisms

1995 ◽  
Vol 268 (4) ◽  
pp. L539-L545 ◽  
Author(s):  
A. T. Canada ◽  
L. A. Herman ◽  
S. L. Young
Keyword(s):  
Defense Mechanisms ◽  
Antioxidant Defense ◽  
Fischer 344 Rats ◽  
Fischer 344 ◽  
Related Difference ◽  
Age Related ◽  
65 H ◽  
Old Rats ◽  
Gpx Activity

The role of animal age in the lethal response to > 98% oxygen has been extensively studied, with the observation that neonatal rats were resistant while mature animals were sensitive. Antioxidant enzymes increased during the oxygen exposure in neonatal but not in mature rats, suggesting they were important in the age-related toxicity difference. Because no studies had compared the response of mature and old rats to hyperoxia, we exposed Fischer 344 rats, aged 2 and 27 mo, to > 98% oxygen. Unexpectedly, the old rats lived significantly longer than young, 114 and 65 h, respectively. No histopathological differences were found to explain the results. Of the antioxidants, only glutathione peroxidase (GPx) activity was higher in the lungs of nonexposed old rats. Superoxide dismutase (SOD) was higher in the young, results opposite those expected if SOD was important in the lethality difference. No antioxidant induction occurred in the old oxygen-exposed rats. These results suggest that although there may be a role for GPx, mechanisms in addition to antioxidant protection and inflammation are likely responsible for the age-related difference in hyperoxia lethality.

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