scholarly journals Skeletal muscle IGF-binding protein-3 and -5 expressions are age, muscle, and load dependent

2003 ◽  
Vol 284 (2) ◽  
pp. E340-E350 ◽  
Author(s):  
Espen E. Spangenburg ◽  
Tsghe Abraha ◽  
Tom E. Childs ◽  
J. Scott Pattison ◽  
Frank W. Booth

The purpose of the current study was to examine IGFBP-3, -4, and -5 mRNA and protein expression levels as a function of muscle type, age, and regrowth from an immobilization-induced atrophy in Fischer 344 × Brown Norway rats. IGFBP-3 mRNA expression in the 4-mo-old animals was significantly higher in the red and white portions of the gastrocnemius muscle compared with the soleus muscle. However, there were no significant differences in IGFBP-3 mRNA expression among any of the muscle groups in the 30-mo-old animals. There were no significant differences in IGFBP-5 mRNA expression in any of the muscle groups, whereas in the 30-mo-old animals there was significantly less IGFBP-5 mRNA expression in the white gastrocnemius compared with the red gastrocnemius muscles. Although IGFBP-3 and -5 proteins were detected in the type I soleus muscle with Western blot analyses, no detection was observed in the type II red and white portions of the gastrocnemius muscle. Aging from adult (18 mo) to old animals (30 mo) was associated with decreases in IGFBP-3 mRNA and protein and IGFBP-5 protein only in the soleus muscle. After 10 days of recovery from 10 days of hindlimb immobilization, IGFBP-3 mRNA and protein increased in soleus muscles from young (4-mo) rats; however, only IGFBP-3 protein increased in the old (30-mo) rats. Whereas there were no changes in IGFBP-5 mRNA expression during recovery, IGFBP-5 protein in the 10-day-recovery soleus muscle did increase in the young, but not in the old, rats. Because one of the functions of IGFBPs is to modulate IGF-I action on muscle size and phenotype, it is hypothesized that IGFBP-3 and -5 proteins may have potential modulatory roles in type I fiber-dominated muscles, aging, and regrowth from atrophy.

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Vikash Kumar ◽  
Chun Yang ◽  
Aron M Geurts ◽  
Mingyu Liang ◽  
Allen W Cowley

Pappa2 is a metalloproteinase which specifically cleaves IGFBP-3 and IGFBP-5 and in turn releases IGF-1. Recently, we have shown that a subcongenic Dahl salt-sensitive (SS) rat strain containing a 0.71 Mbp of chromosome 13 which includes Pappa2 gene from salt-insensitive Brown Norway (26-P strain) is protected significantly (24 mmHg) from salt-induced hypertension (Cowley et al., 2016). Although it is recognized that Pappa2 modulates development of bone size, cranial cartilage and angiogenesis, its role in kidney development and function is unknown. The present study determined the contribution of Pappa2 to nephron development by comparing SS and 26-P rat strains. It was found that Pappa2 mRNA expression was 5-fold higher in embryonic kidney (day 20.5) of the salt-resistant 26-P rats compared with age-matched SS rats. Pappa2 mRNA expression significantly increased with age of kidney reaching a maximum at postnatal day 5 in both strains. Pappa2 mRNA expression at postnatal day 15 was found to be 9-fold higher in the kidney of 26-P compared with SS strain. Immunohistochemistry studies revealed that Pappa2 co-localized with IGFBP-5 in the ureteric bud indicating that Pappa2 could be important for ureteric branching and nephron endowment. Glomerulus/mm 2 was therefore determined by counting total number of glomeruli in kidney sections from pups starting from P0 to P20. The salt-resistant 26-P congenic strain exhibited significantly greater nephron density 9.03 and 7.07 glo/mm 2 compared to 6.89 and 4.85 glo/mm 2 in SS rat at day P15 and P20, respectively. It appears that the Brown Norway pappa2 allele variant prevents the reduced nephron numbers observed in SS rats and thereby protects these congenic rats from salt-induced hypertension.


2005 ◽  
Vol 98 (3) ◽  
pp. 940-946 ◽  
Author(s):  
Christopher R. Woodman ◽  
Elmer M. Price ◽  
M. Harold Laughlin

We tested the hypothesis that increased intraluminal shear stress induces endothelial nitric oxide (NO) synthase (eNOS) mRNA expression and improves endothelium-dependent dilation in senescent soleus muscle feed arteries (SFA) by increasing NO production. SFA were isolated from young (4 mo) and old (24 mo) male Fischer 344 rats and cannulated with two resistance-matched glass micropipettes. SFA were exposed to no flow (NF), low flow (LF), intermediate flow (IF), or high flow (HF) for 4 h. Mean intraluminal shear stress ranged from 0 to 82 dyn/cm2. At the end of the 4-h treatment period, eNOS mRNA expression was assessed in each SFA. eNOS mRNA expression was significantly lower in old NF SFA than in young NF SFA. In old SFA, eNOS mRNA expression was induced by IF (+154%) and HF (+136%), resulting in a level of expression that was not different from that of young SFA. In a separate series of experiments, SFA were pretreated with NF or HF for 4 h, and endothelial function was assessed by examining vasodilator responses to ACh. ACh-induced dilation was less in old NF SFA than young NF SFA. Pretreatment with HF improved ACh-induced dilation in old SFA such that the response was similar to that of young SFA. In the presence of Nω-nitro-l-arginine to inhibit NOS, ACh-induced dilation was inhibited in old HF SFA such that the response was no longer greater than that of old NF SFA. These results indicate that increased intraluminal shear stress induces eNOS mRNA expression and improves endothelium-dependent dilation in senescent SFA by increasing NO production.


2005 ◽  
Vol 99 (2) ◽  
pp. 739-746 ◽  
Author(s):  
Antonios Kyparos ◽  
Daniel L. Feeback ◽  
Charles S. Layne ◽  
Daniel A. Martinez ◽  
Mark S. F. Clarke

Unloading-induced muscle atrophy occurs in the aging population, bed-ridden patients, and astronauts. This study was designed to determine whether dynamic foot stimulation (DFS) applied to the plantar surface of the rat foot can serve as a countermeasure to soleus muscle atrophy normally observed in hindlimb unloaded (HU) rats. Forty-four mature (6 mo old), male Wistar rats were randomly assigned to ambulatory control, HU alone, HU with active DFS (i.e., plantar contact with active inflation), HU with passive DFS (i.e., plantar contact without active inflation), and HU while wearing a DFS boot with no plantar contact groups. Application of active DFS during HU significantly counteracted the atrophic response by preventing ∼85% of the reduction in type I myofiber cross-sectional area (CSA) in the soleus while preventing ∼57% of the reduction in type I myofiber CSA and 43% of the reduction in type IIA myofiber CSA of the medial gastrocnemius muscle. Wearing of a DFS boot without active inflation prevented myofiber atrophy in the soleus of HU animals in a fashion similar to that observed in HU animals that wore an actively inflated DFS boot. However, when a DFS boot without plantar surface contact was worn during HU, no significant protection from HU-induced myofiber atrophy was observed. These results illustrate that the application of mechanical foot stimulation to the plantar surface of the rat foot is an effective countermeasure to muscle atrophy induced by HU.


1996 ◽  
Vol 271 (2) ◽  
pp. R432-R436 ◽  
Author(s):  
M. Suwa ◽  
T. Nakamura ◽  
S. Katsuta

The extent to which muscle fiber composition was determined by genes transmitted from parents and the correlated response of the synergistic muscle were analysed by using successive selection of rats. The foundation population (G0) was prepared by random choice from heterogeneous stock produced by random mating of three strains, Wistar-Imamichi, Fischer 344, and Donryu. Selective mating for a high percentage of fast-twitch fibers (%FT) in the deep portion of the lateral head of the gastrocnemius muscle and random mating were made from G0 to the seventh generation (G7). Successive selection caused a significant increase (P < 0.05) of %FT in the gastrocnemius muscle. The realized heritability for seven generations was 0.29. %FT in the soleus muscle of the selected line also increased (P < 0.05). In addition, significantly positive correlations (P < 0.05) were found between %FT in the gastrocnemius and soleus muscles in G1-G7. We conclude that approximately 29% of the variation of %FT was determined by genes transmitted from parents, and %FT in the gastrocnemius muscle was positively correlated with that of the soleus muscle.


1998 ◽  
Vol 84 (6) ◽  
pp. 1937-1942 ◽  
Author(s):  
L. V. Thompson ◽  
S. A. Johnson ◽  
J. A. Shoeman

This investigation compared how hindlimb unweighting (HU) affected the contractile function of single soleus muscle fibers from 12- and 30-mo-old Fischer 344 Brown Norway F1 Hybrid rats. After 1 wk of HU, functional properties of single permeabilized fibers were studied, and, subsequently, the fiber type was established by myosin heavy chain (MHC) analysis. After HU, the relative mass of soleus declined by 12 and 19% and the relative mass of the gastrocnemius declined by 15 and 13% in 12- and 30-mo-old animals, respectively. In 12-mo-old animals, the peak active force (5.0 ± 0.2 ×10−4 vs. 3.8 ± 0.2 ×10−4 N) and the peak specific tension (92 ± 4 vs. 78 ± 3 kN/m2) were significantly reduced in the MHC type I fibers by 24 and 15%, respectively. In 30-mo-old animals, the peak active force declined by 40% (4.7 ± 0.2 ×10−4vs. 2.8 ± 0. 3 ×10−4 N) and the peak specific tension declined by 30% (79 ± 5 vs. 55 ± 4 kN/m2). The maximal unloaded shortening velocity of the MHC type I fibers increased in 12-mo-old animals (from 1.65 ± 0.12 to 2.59 ± 0.26 fiber lengths/s) and in 30-mo-old animals (from 0.90 ± 0.09 to 1.50 ± 0.10 fiber lengths/s) after HU. Collectively, these data suggest that the effects of HU on single soleus skeletal muscle fiber function occur in both age groups; however, the single MHC type I fibers from the older animals show greater changes than do single MHC type I fibers from younger animals.


2000 ◽  
Vol 80 (2) ◽  
pp. 329-335 ◽  
Author(s):  
C. Bertozzi ◽  
D. Portetelle ◽  
S. Massart ◽  
A. Prandi ◽  
V. Darras ◽  
...  

To improve carcass quality in finishing calves, some breeders use preparations containing corticoids alone or in association with other growth promoters. We have investigated the effects of dexamethasone treatment on insulin-like growth factor-I (IGF-I), IGF-binding proteins (IGFBP-2 and 3) and thyroid hormones (T3, T4, free T4). Limousine male calves were allocated to a control group (C) (n = 18) and a group (n = 18) that received dexamethasone esters (DEX). Blood and hepatic tissue samples were collected at slaughtering. Thyroid hormones and IGF-I plasma levels were measured by RIA and IGFBPs were evaluated by immunoblotting. Hepatic type I 5′deiodinase (5′D-I) activity was determined by enzyme assay and hepatic expression of mRNA for GH receptor, IGF-I, IGFBP-2, IGFBP-3 and type I deiodinase (D-I) was evaluated by dot blot analysis. Plasma IGF-I and IGFBP-3 levels were reduced by the DEX treatment (P < 0.001 and P < 0.01, respectively) while IGFBP-2 was unaffected. Significant plasma changes for IGF-I and IGFBP-3 were not corroborated by hepatic mRNA levels, for which only a slight non-significant decrease was noted. Growth hormone receptor mRNA expression was increased after treatment (P < 0.01). T3 plasma level was higher in DEX animals (P < 0.05) than in C calves. Finally, treatment increased 5′D-I activity in the hepatic tissue (P < 0.001) and seemed to also affect D-I mRNA expression (P = 0.1). In conclusion, dexamethasone ester injection in calves altered some of their endocrinological parameters; this could explain the catabolic action of corticoids in the bovine species. Key words: Calves, corticoids, IGF-I, IGFBPs, thyroid axis


2004 ◽  
Vol 97 (3) ◽  
pp. 1082-1090 ◽  
Author(s):  
Jason C. Gallegly ◽  
Nicole A. Turesky ◽  
Beau A. Strotman ◽  
Cathy M. Gurley ◽  
Charlotte A. Peterson ◽  
...  

Muscle mass is decreased with advancing age, likely due to altered regulation of muscle fiber size. This study was designed to investigate cellular mechanisms contributing to this process. Analysis of male Fischer 344 X Brown Norway rats at 6, 20, and 32 mo of age demonstrated that, even though significant atrophy had occurred in soleus muscle by old age, myofiber nuclear number did not change, resulting in a decreased myonuclear domain. Also, the number of centrally located nuclei was significantly elevated in soleus muscle of 32-mo-old rats, correlating with an increase in gene expression of MyoD and myogenin. Whereas total 5′-bromo-2′deoxyuridine (BrdU)-positive nuclei were decreased at older ages, BrdU-positive myofiber nuclei were increased. These results suggest that, with age, loss of muscle mass is accompanied by increased myofiber nuclear density that involves fusion of proliferative satellite cells, resembling ongoing regeneration. Interestingly, centrally located myofiber nuclei were not BrdU labeled. Rats were subjected to hindlimb suspension (HS) for 7 or 14 days and intermittent reloading during HS for 1 h each day (IR) to investigate how aging affects the response of soleus muscle to disuse and an atrophy-reducing intervention. After 14 days of HS, soleus muscle size was decreased to a similar extent at all three ages. However, myofiber nuclear number and the total number of BrdU-positive nuclei decreased with HS only in the young rats. IR was associated with an attenuation of atrophy in soleus muscles of 6- and 20- but not 32-mo-old rats. Furthermore, IR was associated with an increase in BrdU-positive myofiber nuclei only in young rats. These data indicate that altered satellite cell function with age contributes to the impaired response of soleus muscle to an intervention that attenuates muscle atrophy in young animals during imposed disuse.


2003 ◽  
Vol 285 (1) ◽  
pp. H251-H258 ◽  
Author(s):  
John A. Russell ◽  
Casey A. Kindig ◽  
Brad J. Behnke ◽  
David C. Poole ◽  
Timothy I. Musch

The effects of aging on muscle microvascular structure and function may play a key role in performance deficits and impairment of O2 exchange within skeletal muscle of senescent individuals. To determine the effects of aging on capillary geometry, red blood cell (RBC) hemodynamics, and hematocrit in a muscle of mixed fiber type, spinotrapezius muscles from Fischer 344 × Brown Norway hybrid rats aged 6–8 mo [young (Y); body mass 421 ± 10 g, n = 6] and 26–28 mo [old (O); 561 ± 12 g, n = 6] were observed by high-resolution transmission light microscopy under resting conditions. The percentage of RBC-perfused capillaries (Y: 78 ± 3%; O: 75 ± 2%) and degree of tortuosity and branching (Y: 13 ± 2%; O: 13 ± 2%, additional capillary length) were not different in O vs. Y muscles. Lineal density of RBC-perfused capillaries in O was significantly reduced (Y: 30.7 ± 1.8, O: 22.8 ± 3.1 capillaries/mm; P < 0.05). However, RBC-perfused capillaries from O rats ( n = 78) exhibited increased RBC velocity ( VRBC) (Y: 219 ± 12, O: 310 ± 14 μm/s; P < 0.05) and RBC flux ( FRBC) (Y: 27 ± 2, O: 41 ± 2 RBC/s; P < 0.05) vs. Y rats ( n = 66). Thus O2 delivery per unit of muscle was not different between groups (Y: 894 ± 111, O: 887 ± 118 RBC · s-1 · mm muscle-1). Capillary hematocrit was not different in Y vs. O rats (Y: 26 ± 1%, O: 28 ± 1%: P > 0.05). These data indicate that in resting spinotrapezius muscle, aging decreases the lineal density of RBC-perfused capillaries while increasing mean VRBC and FRBC within those capillaries. Whereas muscle conductive O2 delivery and capillary hematocrit were unchanged, elevated VRBC reduces capillary RBC transit time and may impair the diffusive transport of O2 from blood to myocyte particularly under exercise conditions.


2003 ◽  
Vol 285 (4) ◽  
pp. R733-R740 ◽  
Author(s):  
Yuk-Chow Ng ◽  
Murali Nagarajan ◽  
Korinne N. Jew ◽  
Lisa C. Mace ◽  
Russell L. Moore

The present study tests the hypothesis that endurance exercise training (ETr) reverses age-associated alterations in expression of Na+-K+-ATPase subunit isoforms in rat skeletal muscles. Expression of the isoforms was examined in 16-mo-old sedentary middle-aged, 29-mo-old sedentary senescent, and 29-mo-old treadmill exercise-trained senescent Fischer 344 × Brown Norway rats. Levels of the α1-isoform increased with age in red gastrocnemius (GR), white gastrocnemius (GW), and extensor digitorum longus (EDL) muscles, and ETr further increased its levels. Levels of the α2-isoform were unchanged in GR, had a strong trend for a decrease in GW, and decreased significantly in EDL. ETr increased expression of the α2-isoform in all three muscle groups. There was no increase in expression of the β1-isoform in GR, GW, or EDL with age, whereas ETr markedly increased its levels in the muscles. There was a marked decrease with age in expression of the β2-isoform in the muscle groups that was not reversed by ETr. By contrast, β3-isoform levels increased with age in GR and GW, and ETr was able to reverse this increase. Na+-K+-ATPase enzyme activity was unchanged with age in GR and GW but increased in EDL. ETr increased enzyme activity in GR and GW and did not change in EDL. Myosin heavy chain isoforms in the muscle groups did not change significantly with age; ETr caused a general shift toward more oxidative fibers. Thus ETr differentially modifies age-associated alterations in expression of Na+-K+-ATPase subunit isoforms, and a mechanism(s) other than physical inactivity appears to play significant role in some of the age-associated changes.


2000 ◽  
Vol 88 (4) ◽  
pp. 1265-1270 ◽  
Author(s):  
E. R. Blough ◽  
J. K. Linderman

To examine the effect of extreme old age on muscle plasticity, 6- (adult) and 36-mo-old (old) male Fischer 344 × Brown Norway hybrid rats underwent bilateral surgical ablation of the gastrocnemius muscle to functionally overload (OV) the fast-twitch plantaris muscle for 8 wk. Plantaris muscle wet weight, muscle cross-sectional area (CSA), and average fiber CSA decreased by 44, 42, and 40%, respectively, in old compared with adult rats, and peak isometric tetanic tension decreased by 83%. Compared with muscles in age-matched controls, plantaris muscle mass increased by 53% and type I, IIA, and IIX/IIB CSA increased by 91, 76, and 103%, respectively, in adult-OV rats, but neither wet mass nor fiber CSA increased in old-OV rats. OV decreased type I, IIA, and IIX/IIB mean fiber CSA by 31, 35, and 30%, respectively, in old-OV rats. Collectively, our data indicate that in extreme old age the plantaris muscle undergoes significant loss of mass, fiber CSA, and contractile function, as well as its capacity to undergo hypertrophy in response to a chronic increase in mechanical load.


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