Search

We sought to delineate the effects of acute and chronic exercise on the regulation of intracellular nitric oxide (N[O.sub.i]) production in putative endothelial progenitor cells (EPCs). Putative EPC colony-forming units (CFU-EC) were cultured from blood drawn before and after 30 min of treadmill exercise at 75% of maximal oxygen uptake in active (n = 8) and inactive (n = 8) men. CFU-EC were similar between groups at baseline, but increased after exercise in active men only (P = 0.04). CFU-EC expressed Dower NADPH oxidase subunit [gp91.sup.phox] mRNA and elevated endothelial nitric oxide synthase mRNA in active relative to inactive men at baseline (P < 0.05). Acute exercise reduced [gp91.sup.phox] mRNA in CFU-EC of both groups (P < 0.05), whereas [p47.sup.phox] mRNA levels were reduced in the inactive group only (P = 0.02). There were no differences between groups or with acute exercise in xanthine oxidase, superoxide dismutase isoforms, or gluthathione peroxidase-1 mRNA levels. N[O.sub.i] was significantly greater in CFU-EC of active men at baseline (P = 0.004). N[O.sub.i] increased in CFU-EC of inactive men with acute exercise, and in vitro experiments with apocynin indicated the increased N[O.sub.i] production was caused by suppression of NADPH oxidase. However, the increases in N[O.sub.i] with the different treatments in the inactive group did not reach the baseline levels in the active group (P < 0.05). We conclude that acute exercise increases N[O.sub.i] in cells generated by the CFU-EC assay through an NADPH oxidase-inhibition mechanism in sedentary men. However, differences due to chronic exercise must involve additional factors. Our findings support exercise as a means to improve putative EPC function and suggest a novel mechanism that may explain this effect. physical activity; angiogenesis; oxidative stress doi: 10.1152/ajpheart.00347.2009.

Currently, the repertoire of cellular and molecular pathways that control skeletal muscle atrophy and hypertrophy are not well defined. It is possible that intracellular regulatory signaling pathways are active at different times during the muscle hypertrophy process. The hypothesis of the given experiments was that cellular signals related to protein translation would be active at early time points of skeletal muscle regrowth, whereas transcriptional signals would be active at later time points of skeletal muscle regrowth. The phosphorylation status of p38 MAPK and JNK increased at the end of limb immobilization but returned to control values at recovery day 3. Transient increases in phosphorylation and in protein concentration occurred during recovery of soleus muscle mass. Phosphorylation of Akt, [p70.sup.S6k], and signal transducer and activator of transcription 3 (STAT3) peaked on recovery day 3 compared with day 0. Glycogen synthase kinase (GSK)-3[beta] phosphorylation was increased on the sixth and fifteenth recovery day. In addition, transient peaks in seven protein concentrations occurred at different times of recovery: STAT3, calcineurin A (CaNA), CaNB, and [beta]4E-BP1 protein concentrations peaked on the third recovery day; [p70.sup.S6k], STAT3, Akt, and GSK3-[beta] peaked on the sixth recovery day; and GSK3-[beta] peaked on the fifteenth recovery day. The apexes of STAT3 and GSK3-[beta] protein concentrations remained elevated for two recovery time points. Thus the time course of increase in molecules of signaling pathways differed as the young rat soleus muscle regrew from an atrophied state. skeletal muscle; hypertrophy; rehabilitation; atrophy

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 x 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 tauscie 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. insulin-like growth factor-binding protein; insulin-like growth factor I; growth; hypertrophy; fiber type

To determine whether changes in glycogen synthase kinase-3[beta] (GSK-3[beta]) phosphorylation contribute to muscle hypertrophy, we delineated the effects of GSK-3[beta] activity on [C.sub.2][C.sub.12] myotube size. We also examined possible insulin-like growth factor I (IGF-I) signaling of NFAT (nuclear factors of activated T cells)-inducible gene activity and possible modulation of NFAT activation by GSK-3[beta]. Application of IGF-I (250 ng/ml) or LiCl (10 mM) alone (i.e., both inhibit GSK-3[beta] activity) increased the area of [C.sub.2][C.sub.12] myotubes by 80 and 85%, respectively. The application of IGF-I (250 ng/ml) elevated GSK-3[beta] phosphorylation and reduced GSK-3[beta] kinase activity by ~800% and ~25%, respectively. LY-294002 (100 [micro] M) and wortmannin (150 [micro]M), specific inhibitors of phosphatidylinositol 3'-kinase, attenuated IGF-I-induced GSK-3[beta] phosphorylation by 67 and 92%, respectively. IGF-I suppressed the kinase activity of GSK-3[beta]. IGF-I (250 ng/ml), but not LiCl (10 mM), induced an increase in NFAT-activated luciferase reporter activity. Cotransfection of a constitutively active GSK-3[beta] (cGSK-3[beta]) inhibited the induction by IGF-I of NFAT-inducible reporter activity. LiCl, which inhibits GSK3[beta], removed the block by cGSK-3[beta] on IGF-I-inducible NFAT-responsive reporter gene activity. These data suggest that the IGF-I-induced increase in skeletal myotube size is signaled, in part, through the inhibition of GSK-3[beta]. skeletal muscle; signaling; glycogen synthase kinase-3[beta]; insulin-like growth factor I; nuclear factors of activated T cells

Multiple signaling pathways mediate LIF-induced skeletal muscle satellite cell proliferation. Am J Physiol Cell Physiol 283: C204-C211, 2002. First published March 6, 2002; 10.1152/ ajpcell.00574.2001.--There are many known growth factors/ cytokines that induce skeletal muscle satellite cell proliferation. Currently, the signaling mechanisms in which these growth factors/cytokines activate satellite cell proliferation are not completely understood. Here, we sought to determine signaling mechanisms by which leukemia inhibitory factor (LIF) induces satellite cell proliferation in culture. First, we confirmed that LIF induces proliferation of [C.sub.2][C.sub.12] immortalized myoblasts and cultured primary rat satellite cells. In addition, we also found that this increase in proliferation can be inhibited by incubation of the cells in tyrphostin AG 490, a specific inhibitor of Janus-activated kinase (JAK) 2 activity. Furthermore, we also found that incubation of the cells at various time points with LIF (10 ng/ml) induces a significant, transient increase in JAK2 phosphorylation, signal transducers and activators of transcription (STAT3) phosphorylation, and STAT3 transcriptional activity. Increases in the STAT3-sensitive endogenous SOC3 protein followed these transient increases in STAT3 activation. In addition, AG 490 inhibited the increase in STAT3 phosphorylation. Finally, LIF did not change the phosphorylation status of extracellular signal-regulated protein kinase (ERK)1/2 or affect the phosphorylation status of Akt/protein kinase B. However, LY-294002, an inhibitor of phosphoinositide 3-kinase, blocked LIF-induced proliferation of satellite cells. These data suggest that LIF induces satellite cell proliferation by activation of the JAK2-STAT3 signaling pathway, suggesting that this may be an important pathway in muscle growth and/or hypertrophy. cytokine; mitogen; Janus-activated kinase; leukemia inhibitory factor; signal transducers and activators of transcription

This article discusses the relationship between insulin-like growth factor, cell proliferation, muscle growth, and muscular atrophy prevention.

The effects of physical activity on the uptake and release of calcium ions from the sarcoplasmic reticulum (SR) are investigated using isolated frog sartorius muscle preparations. Activities are classified as constant fatigue or constant duration. Results from constant fatigue experiments reveal that the depression of SR function is independent of the activity protocol. However, when there is imposition of a constant duration in activity, SR function correlate well with force reduction.

The study is divided in to two parts, the first dealing with the cell and the molecular biology of muscle in terms of growth and the second deals with physiological mechanism involved in the alteration of size of the human muscle mass. This study would benefit physicians, physiotherapist and kinesiologists.

Spangenburg, Espen E., Jay H. Williams, Roland R. Roy, and Robert J. Talmadge. Skeletal muscle calcineurin: influence of phenotype adaptation and atrophy. Am J Physiol Regulatory Integrative Comp Physiol 280: R1256-R1260, 2001.--Calcineurin (CAN) has been implicated as a signaling molecule that can transduce physiological stimuli (e.g., contractile activity) into molecular signals that initiate slow-fiber phenotypic gene expression and muscle growth. To determine the influence of muscle phenotype and atrophy on CaN levels in muscle, the levels of soluble CaN in rat muscles of varying phenotype, as assessed by myosin heavy chain (MHC)-isoform proportions, were determined by Western blotting. CaN levels were significantly greater in the plantaris muscle containing predominantly fast (IIx and IIb) MHC isoforms, compared with the soleus (predominantly type I MHC) or vastus intermedius (VI, contains all 4 adult MHC isoforms). Three months after a complete spinal cord transection (ST), the CaN levels in the VI muscle were significantly reduced, despite a significant increase in fast MHC isoforms. Surprisingly, the levels of CaN in the VI were highly correlated with muscle mass but not MHC isoform proportions in ST and control rats. These data demonstrate that CaN levels in skeletal muscle are highly correlated to muscle mass and that the normal relationship with phenotype is lost after ST. calcium; calmodulin; myosin heavy chain; nuclear factor of activated T cells