scholarly journals Increased Adenine Nucleotide Degradation in Skeletal Muscle Atrophy

2019 ◽  
Vol 21 (1) ◽  
pp. 88 ◽  
Author(s):  
Spencer G. Miller ◽  
Paul S. Hafen ◽  
Jeffrey J. Brault
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Intracellular Signaling ◽  
Adenine Nucleotide ◽  
Degradation Products ◽  
Adenine Nucleotides ◽  
Skeletal Muscle Atrophy ◽  
Valuable Insight ◽  
Disease States ◽  
Nucleotide Degradation

Adenine nucleotides (AdNs: ATP, ADP, AMP) are essential biological compounds that facilitate many necessary cellular processes by providing chemical energy, mediating intracellular signaling, and regulating protein metabolism and solubilization. A dramatic reduction in total AdNs is observed in atrophic skeletal muscle across numerous disease states and conditions, such as cancer, diabetes, chronic kidney disease, heart failure, COPD, sepsis, muscular dystrophy, denervation, disuse, and sarcopenia. The reduced AdNs in atrophic skeletal muscle are accompanied by increased expression/activities of AdN degrading enzymes and the accumulation of degradation products (IMP, hypoxanthine, xanthine, uric acid), suggesting that the lower AdN content is largely the result of increased nucleotide degradation. Furthermore, this characteristic decrease of AdNs suggests that increased nucleotide degradation contributes to the general pathophysiology of skeletal muscle atrophy. In view of the numerous energetic, and non-energetic, roles of AdNs in skeletal muscle, investigations into the physiological consequences of AdN degradation may provide valuable insight into the mechanisms of muscle atrophy.

Intracellular signaling during skeletal muscle atrophy

2006 ◽  
Vol 33 (2) ◽  
pp. 155-165 ◽  
Author(s):  
Susan C. Kandarian ◽  
Robert W. Jackman
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Intracellular Signaling ◽  
Skeletal Muscle Atrophy

Adenine nucleotide degradation in slow-twitch red muscle

1990 ◽  
Vol 258 (2) ◽  
pp. C258-C265 ◽  
Author(s):  
P. C. Tullson ◽  
D. M. Whitlock ◽  
R. L. Terjung
Keyword(s):  
Soleus Muscle ◽  
High Performance ◽  
Adenine Nucleotide ◽  
Degradation Products ◽  
Adenine Nucleotides ◽  
Extended Period ◽  
Red Muscle ◽  
Slow Twitch ◽  
Nucleotide Degradation ◽  
Purine Degradation

The catabolism of adenine nucleotides (AdN) in rat soleus muscle (predominantly slow twitch) is very different from that in fast-twitch muscle. AMP deaminase is highly inhibited during brief (3 min) intense (120 tetani/min) in situ stimulation, resulting in little inosine 5'-monophosphate (IMP) accumulation (0.21 mumol/g). Even with ligation of the femoral artery during the same brief intense contraction conditions there is surprisingly little increase in IMP (0.37 mumol/g), although AdN depletion is evident (-1.30 mumol/g). We have tested the hypothesis that accumulation of purine nucleosides and bases accounts for the AdN depletion by measuring purine degradation products using high-performance liquid chromatography. There was no stoichiometric accumulation of purine degradation products to account for the observed AdN depletion even though metabolite recovery was essentially quantitative. We hypothesis that under these conditions AdN are converted to a form different from purine nucleoside and base degradation products. In contrast to the inhibition of AMP deamination seen during brief ischemia, slow-twitch muscle depletes a substantial fraction (28%) of muscle AdN (1.75 mumol/g) that can be accounted for stoichiometrically as purine degradation products during an extended 10-min ischemic period of mild (12 tetani/min) contraction conditions. IMP accumulation (1 mumol/g) is most prominent with inosine, accounting for 23% (0.4 mumol/g) of the depleted AdN, showing that slow-twitch red muscle is capable of both AMP deamination and the subsequent production of purine nucleosides during an extended period of ischemic contractions. The present results indicate that AdN metabolism in the soleus muscle is complex, yielding expected degradation products or a loss of total purines, depending on contraction conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Energy metabolism and adenine nucleotide degradation in twitch-stimulated rat hindlimb during ischemia-reperfusion

1993 ◽  
Vol 264 (4) ◽  
pp. E655-E661 ◽  
Author(s):  
D. G. Welsh ◽  
M. I. Lindinger
Keyword(s):  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Time Course ◽  
Ischemia Reperfusion Injury ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Ischemia Reperfusion ◽  
Control Period ◽  
High Energy ◽  
Nucleotide Degradation

The purpose of this study was to characterize twitch tension and energy metabolism in ischemic, stimulated rat hindlimb to determine its suitability as a rapid time course model of ischemia-reperfusion injury. After 15 min equilibration, rat hindlimbs were stimulated (1-Hz twitches, 0.2 ms pulse duration, 15 V) for 5 min (control, n = 8). This twitch protocol was maintained throughout the ischemic and reperfusion periods. The control period was followed by 5, 20, or 40 min of ischemia (ligation of femoral artery and vein) or 40 min of ischemia with 0, 5, or 20 min of reperfusion (removal of ligature). The soleus [89% slow oxidative (SO)] and the white gastrocnemius [WG; 91% fast glycolytic (FG)] were analyzed for phosphocreatine (PCr), adenine nucleotides, glycogen, and glycolytic intermediates. Ischemia was characterized by progressive decreases in twitch tension, high-energy phosphagens, total adenine nucleotides (TAN), and glycogen. Also, energy metabolism was altered at a greater rate in WG than in soleus. Reperfusion resulted in a recovery in PCr and lactate, with little change in ATP, TAN, or glycogen. The inability to resynthesize adenine nucleotides and glycogen during reperfusion is characteristic of damaged skeletal muscle. The extent of the metabolic alterations in SO and FG muscles during twitch stimulation was comparable with previously reported noncontracting ischemia protocols of 2-4 and 4-7 h in length, respectively. The present study demonstrates that twitch stimulation of ischemic skeletal muscle is a useful model for inducing rapid metabolic changes and an ischemic insult comparable to prolonged noncontracting ischemia-reperfusion models.

scholarly journals IL-6-induced skeletal muscle atrophy

2005 ◽  
Vol 98 (3) ◽  
pp. 911-917 ◽  
Author(s):  
F. Haddad ◽  
F. Zaldivar ◽  
D. M. Cooper ◽  
G. R. Adams
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Muscle Atrophy ◽  
Intracellular Signaling ◽  
Skeletal Muscle Atrophy ◽  
Growth Factor Signaling ◽  
Low Level ◽  
Healthy Elderly ◽  
Ribosomal S6 Kinase

Chronic, low-level elevation of circulating interleukin (IL)-6 is observed in disease states as well as in many outwardly healthy elderly individuals. Increased plasma IL-6 is also observed after intense, prolonged exercise. In the context of skeletal muscle, IL-6 has variously been reported to regulate carbohydrate and lipid metabolism, increase satellite cell proliferation, or cause muscle wasting. In the present study, we used a rodent local infusion model to deliver modest levels of IL-6, comparable to that present after exercise or with chronic low-level inflammation in the elderly, directly into a single target muscle in vivo. The aim of this study was to examine the direct effects of IL-6 on skeletal muscle in the absence of systemic changes in this cytokine. Data included cellular and molecular markers of cytokine and growth factor signaling (phosphorylation and mRNA content) as well as measurements to detect muscle atrophy. IL-6 infusion resulted in muscle atrophy characterized by a preferential loss of myofibrillar protein (−17%). IL-6 induced a decrease in the phosphorylation of ribosomal S6 kinase (−60%) and STAT5 (−33%), whereas that of STAT3 was increased approximately twofold. The changes seen in the IL-6-infused muscles suggest alterations in the balance of growth factor-related signaling in favor of a more catabolic profile. This suggests that downregulation of growth factor-mediated intracellular signaling may be a mechanism contributing to the development of muscle atrophy induced by elevated IL-6.

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