Proteasome proteolytic activity in skeletal muscle is increased in patients with sepsis

2007 ◽  
Vol 112 (9) ◽  
pp. 499-506 ◽  
Author(s):  
Maria Klaude ◽  
Katarina Fredriksson ◽  
Inga Tjäder ◽  
Folke Hammarqvist ◽  
Bo Ahlman ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Proteolytic Activity ◽  
Prolonged Mechanical Ventilation ◽  
Multiple Organ ◽  
Proteasome Activity ◽  
Control Group ◽  
Icu Patients ◽  
Leg Muscles ◽  
Skeletal Muscle Wasting ◽  
Leg Muscle

Patients with sepsis in the ICU (intensive care unit) are characterized by skeletal muscle wasting. This leads to muscle dysfunction that also influences the respiratory capacity, resulting in prolonged mechanical ventilation. Catabolic conditions are associated with a general activation of the ubiquitin–proteasome pathway in skeletal muscle. The aim of the present study was to measure the proteasome proteolytic activity in both respiratory and leg muscles from ICU patients with sepsis and, in addition, to assess the variation of proteasome activity between individuals and between duplicate leg muscle biopsy specimens. When compared with a control group (n=10), patients with sepsis (n=10) had a 30% (P<0.05) and 45% (P<0.05) higher proteasome activity in the respiratory and leg muscles respectively. In a second experiment, ICU patients with sepsis (n=17) had a 55% (P<0.01) higher proteasome activity in the leg muscle compared with a control group (n=10). The inter-individual scatter of proteasome activity was larger between the patients with sepsis than the controls. We also observed a substantial intra-individual difference in activity between duplicate biopsies in several of the subjects. In conclusion, the proteolytic activity of the proteasome was higher in skeletal muscle from patients with sepsis and multiple organ failure compared with healthy controls. It was shown for the first time that respiratory and leg muscles were affected similarly. Furthermore, the variation in proteasome activity between individuals was more pronounced in the ICU patients for both muscle types, whereas the intra-individual variation between biopsies was similar for ICU patients and controls.

scholarly journals Skeletal muscle and liver protein degradation in mice divergently selected for low and high body weight over 108 generations

2005 ◽  
Vol 48 (5) ◽  
pp. 505-517 ◽  
Author(s):  
S. J. Rosochacki ◽  
E. Wirth-Dzięciołowska ◽  
M. Zimowska ◽  
T. Sakowski ◽  
J. Połoszynowicz ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Weight ◽  
Cell Size ◽  
Cathepsin D ◽  
Liver Protein ◽  
Protein Catabolism ◽  
Leg Muscles ◽  
Leg Muscle ◽  
And Control ◽  
Old Mice

Abstract. Experiment was carried out on 111 and 13-14 weeks old mice divergently selected for low (L) and high (C) body weight over 108 generations. In leg muscle and liver cathepsin D (CatD) was determined as pepstatin sensitive activity (PSCatD), and as pepstatin-insensitive (PIA) and leupeptin-insensitive (LIA) acid autolytic activities (AAA) were measured. In leg muscle and liver all measured activities were higher in L as compared to C and control (K) mice. The percent of inhibition of LIA was lower in L then C mice in both examined tissues. In the leg muscles, in L mice protein catabolism was mostly influenced by CatD, but in the liver CatD was mostly active in K mice. CatD, PSCatD, AAA and LIA in leg muscle of L mice as compare to K were higher in female (F) by 68 %, 68.5 %, 91.3 % and 94.5 %, respectively, and in male (M) mice by 43.4 %, 54 %, 47.1 % and 64 %, respectively. The percent of inhibition by leupeptin in AAA was higher in C mice by 61.9 % in F and by 40 % in M mice. In the liver, PIA was higher by about 45 % in L and by 28.5 % in C mice as compare to K ones. There were about 36% of 30.00-39.99 μm muscle fibrils in M mice and in males of L group 40.00-49.99 μm fibrils appeared at 25% (absent in 3 weeks mice). In female, all measured fibril diameters were in higher percent in L than in C group. RNA variables were higher by about 25% (in average) in C as compare to K and L groups. Functional cell size (FCS) was lowered in L and C group as compared to K by about 10 % (in average). These results indicate on faster proteins turnover in L than in C group of mice.

scholarly journals Thoracic skeletal muscle quantification using computed tomography and prognosis of elderly ICU patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sung Woo Moon ◽  
Song Yee Kim ◽  
Ji Soo Choi ◽  
Ah Young Leem ◽  
Su Hwan Lee ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Prolonged Mechanical Ventilation ◽  
Significant Risk ◽  
Pectoralis Muscle ◽  
Muscle Loss ◽  
Icu Patients ◽  
Icu Admission ◽  
Icu Stay ◽  
Prolonged Ventilation ◽  
Skeletal Muscle Loss

AbstractIn elderly ICU patients, the prevalence of skeletal muscle loss is high. Longitudinal effect of thoracic muscles, especially in elderly ICU patients, are unclear although skeletal muscle loss is related with the short- and long-term outcomes. This study aimed to evaluate whether pectoralis muscle mass loss could be a predictor of prognosis in elderly ICU patients. We retrospectively evaluated 190 elderly (age > 70 years) patients admitted to the ICU. We measured the cross-sectional area (CSA) of the pectoralis muscle (PMCSA) at the fourth vertebral region. CT scans within two days before ICU admission were used for analysis. Mortality, prolonged mechanical ventilation, and longitudinal changes in Sequential Organ Failure Assessment (SOFA) scores were examined. PMCSA below median was significantly related with prolonged ventilation (odds ratio 2.92) and a higher SOFA scores during the ICU stay (estimated mean = 0.94). PMCSA below median was a significant risk for hospital mortality (hazards ratio 2.06). In elderly ICU patients, a low ICU admission PMCSA was associated with prolonged ventilation, higher SOFA score during the ICU stay, and higher mortality. Adding thoracic skeletal muscle CSA at the time of ICU admission into consideration in deciding the therapeutic intensity in elderly ICU patients may help in making medical decisions.

scholarly journals Skeletal Muscle Transcriptome Analysis of Hanzhong Ma Duck at Different Growth Stages Using RNA-Seq

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 315
Author(s):  
Zhigang Hu ◽  
Junting Cao ◽  
Jianqin Zhang ◽  
Liyan Ge ◽  
Huilin Zhang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
Anas Platyrhynchos ◽  
Breast Muscle ◽  
Growth Stages ◽  
Rna Seq ◽  
Leg Muscles ◽  
Exon Splicing ◽  
Annotation Information ◽  
Leg Muscle

As one of the most important poultry worldwide, ducks (Anas platyrhynchos) are raised mainly for meat and egg products, and muscle development in ducks is important for meat production. Therefore, an investigation of gene expression in duck skeletal muscle would significantly contribute to our understanding of muscle development. In this study, twenty-four cDNA libraries were constructed from breast and leg muscles of Hanzhong Ma ducks at day 17, 21, 27 of the embryo and postnatal at 6-month-old. High-throughput sequencing and bioinformatics were used to determine the abundances and characteristics of transcripts. A total of 632,172,628 (average 52,681,052) and 637,213,938 (average 53,101,162) reads were obtained from the sequencing data of breast and leg muscles, respectively. Over 71.63% and 77.36% of the reads could be mapped to the Anas platyrhynchos genome. In the skeletal muscle of Hanzhong duck, intron variant (INTRON), synonymous variant (SYNONYMOUS_CODING), and prime 3′ UTR variant (UTR_3_PRIME) were the main single nucleotide polymorphisms (SNP) annotation information, and “INTRON”, “UTR_3_PRIME”, and downstream-gene variant (DOWNSTREAM) were the main insertion-deletion (InDel) annotation information. The predicted number of alternative splicing (AS) in all samples were mainly alternative 5′ first exon (transcription start site)-the first exon splicing (TSS) and alternative 3′ last exon (transcription terminal site)-the last exon splicing (TTS). Besides, there were 292 to 2801 annotated differentially expressed genes (DEGs) in breast muscle and 304 to 1950 annotated DEGs in leg muscle from different databases. It is worth noting that 75 DEGs in breast muscle and 49 DEGs in leg muscle were co-expressed at all developmental points of comparison, respectively. The RNA-Seq data were confirmed to be reliable by qPCR. The identified DEGs, such as CREBL2, RHEB, GDF6, SHISA2, MYLK2, ACTN3, RYR3, and STMN1, were specially highlighted, indicating their strong associations with muscle development in the Hanzhong Ma duck. KEGG pathway analysis suggested that regulation of actin cytoskeleton, oxidative phosphorylation, and focal adhesion were involved in the development of skeletal muscle. The findings from this study can contribute to future investigations of the growth and development mechanism in duck skeletal muscle.

The ubiquitin–proteasome system and skeletal muscle wasting

2005 ◽  
Vol 41 (1) ◽  
pp. 173 ◽  
Author(s):  
Didier Attaix ◽  
Sophie Ventadour ◽  
Audrey Codran ◽  
Daniel Béchet ◽  
Daniel Taillandier ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Wasting ◽  
Ubiquitin Proteasome System ◽  
Skeletal Muscle Wasting ◽  
Ubiquitin Proteasome

Glacial Acetic Acid Catalyzed Synthesis, Physicochemical and Biological Evaluation of Benzodiazepines as Potent CNS Agents

2019 ◽  
Vol 19 (2) ◽  
pp. 146-151
Author(s):  
Vipin Kumar ◽  
Shweta Verma ◽  
Sushil Kumar
Keyword(s):  
Skeletal Muscle ◽  
Muscle Relaxant ◽  
Treated Group ◽  
Biological Evaluation ◽  
Log P ◽  
Control Group ◽  
Skeletal Muscle Relaxant ◽  
Benzodiazepine Derivatives ◽  
Chloro Group ◽  
Muscle Relaxant Activity

Background: Approach for green chemistry for chemical synthesis is found to be very efficient as it makes the reaction more easily, less tedious, maximize desired products and minimize by-products. Materials & Methods: Utilizing this approach 1, 5-benzodiazepines and its derivatives have been synthesized and evaluated for skeletal muscle and antianxiety activity. 1, 5-benzodiazepine derivatives have attracted great attention due to its diversity of pharmacological activities and its application in heterocyclic synthesis and medicines. The target compounds were synthesized by first reacting o-phenylenediamine with acetophenone to yield 1, 5-benzodiazepines. In the next step the NH of 1, 5-benzodiazepines were chloroacetylated and then the chloro group was substituted with different anilines. The structures were confirmed on the basis of their TLC, IR, 1H NMR and CHN elemental studies. The physicochemical parameters were determined for BBB penetration through online software. Results: The Log P values of the compounds tested showed that compounds have the potential to be CNS active. The compounds were evaluated for the skeletal muscle relaxant activity and antianxiety activity. It was investigated that 1, 5-benzodiazepines derivatives possess significant differences between control group and treated group. Conclusion: Among these derivatives, the compound bearing chloro group possesses the highest skeletal muscle relaxant and antianxiety activity.

Effects ofS-nitroso-N-acetylcysteine on contractile function of reperfused skeletal muscle

1998 ◽  
Vol 274 (3) ◽  
pp. R822-R829 ◽  
Author(s):  
Long-En Chen ◽  
Anthony V. Seaber ◽  
Rima M. Nasser ◽  
Jonathan S. Stamler ◽  
James R. Urbaniak
Keyword(s):  
Skeletal Muscle ◽  
Reperfusion Injury ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Protective Role ◽  
Control Group ◽  
Group Vi ◽  
No Donor ◽  
Early Reperfusion ◽  
Reconstructive Operations

The ultimate goal of replantation and microsurgical reconstructive operations is to regain or improve impaired function of the tissue. However, the data related to the influence of NO on tissue function are limited. This study evaluated the effects of the NO donor S-nitroso- N-acetylcysteine (SNAC) on contractile function of skeletal muscle during reperfusion. Forty-nine rats were divided into six groups. The extensor digitorum longus (EDL) muscles in groups I and II were not subjected to ischemia-reperfusion but were treated with a low (100 nmol/min) or high (1 μmol/min) dose of SNAC. In groups III- V, the EDL underwent 3 h of ischemia and 3 h of reperfusion and was also treated with low (100 nmol/min) or high doses (1 or 5 μmol/min) of SNAC. Group VI was a phosphate-buffered saline (PBS)-treated control group. Twenty additional animals were used to document systemic effects of SNAC and PBS only. SNAC or PBS was infused for 6.5 h, beginning 30 min before ischemia and continuing throughout the duration of reperfusion. Contractile testing compared the maximal twitch force, isometric tetanic contractile forces, fatigue, and fatigue half time of the experimental EDL and the contralateral nontreated EDL. The findings indicate that 1) SNAC does not influence contractile function of EDL muscle not subjected to ischemia-reperfusion, 2) SNAC significantly protects the contractile function of ischemic skeletal muscle against reperfusion injury in the early reperfusion period, and 3) the protective role of SNAC is critically dosage dependent; protection is lost at higher doses. The conclusion from this study is that supplementation with exogenous NO exerts a protective effect on the tissue against reperfusion injury.

scholarly journals PSIX-29 JAK2-STAT3 Pathway Mediated Satellite Cell Apoptosis to Govern Skeletal Muscle Growth with Lysine

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 334-334
Author(s):  
Zhi-wen Song ◽  
Cheng-long Jin ◽  
Mao Ye ◽  
Chun-qi Gao ◽  
Hui-chao Yan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Growth ◽  
Longissimus Dorsi ◽  
Control Group ◽  
Stat3 Pathway ◽  
Skeletal Muscle Growth ◽  
Longissimus Dorsi Muscle ◽  
Dorsi Muscle ◽  
Pathway Inhibition ◽  
Induced Apoptosis

Abstract Apoptosis is programmed cell death that can be stimulated by external stress or nutrition restrictions. Lysine (Lys) is an essential amino acid for pig growth, and the relationship between Lys deficiency caused apoptosis and inhibition of skeletal muscle growth remains unknown. The objective of this study was to investigate whether apoptosis could be regulated by Lys supplementation and the potential mechanism. In current work, 30 male Duroc × Landrace × Large weaned piglets were divided randomly into 3 groups: control group (Lys 1.30%), Lys deficiency group (Lys 0.86%), and Lys rescue group (Lys 0.86%, 0-14d; 1.30%,15–28 d). The experiment lasted for 28 days, and on the morning of 29 d, piglets were slaughtered to collect samples. Isobaric tag for relative and absolute quantification (iTRAQ) proteomics analysis of the longissimus dorsi muscle showed that Janus family tyrosine kinase (JAK)-signal transducer and activator of transcription (STAT) pathway was involved in Lys deficiency-induced apoptosis and inhibited skeletal muscle growth. Meanwhile, western blotting results of the longissimus dorsi muscle demonstrated that Lys deficiency caused apoptosis (P &lt; 0.05) with the JAK2-STAT3 pathway inhibition (P &lt; 0.05). Interestingly, apoptosis was suppressed (P &lt; 0.05), and the JAK2-STAT3 pathway was reactivated (P &lt; 0.05) after Lys re-supplementation in longissimus dorsi muscle. In addition, results of satellite cells (SCs) isolated from the longissimus dorsi muscle of 5-day-old Landrace piglets showed that Lys deficiency-induced apoptosis (P &lt; 0.05) was mediated by the JAK2-STAT3 pathway inhibition (P &lt; 0.05). Moreover, the JAK2-STAT3 pathway was reactivated (P &lt; 0.05) by Lys re-supplementation and suppressed apoptosis in SCs (P &lt; 0.05), and this effect was blocked (P &lt; 0.05) after SCs treated with AG-490 (a specific inhibitor of JAK2). Collectively, Lys inhibited apoptosis in SCs to govern skeletal muscle growth via the JAK2-STAT3 pathway.

scholarly journals Mitochondrial Dysfunction Is a Common Denominator Linking Skeletal Muscle Wasting Due to Disease, Aging, and Prolonged Inactivity

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 588
Author(s):  
Hayden W. Hyatt ◽  
Scott K. Powers
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
Chronic Diseases ◽  
Muscle Mass ◽  
Cancer Chemotherapy ◽  
Muscle Wasting ◽  
The Body ◽  
Common Denominator ◽  
Skeletal Muscle Wasting ◽  
Vital Functions

Skeletal muscle is the most abundant tissue in the body and is required for numerous vital functions, including breathing and locomotion. Notably, deterioration of skeletal muscle mass is also highly correlated to mortality in patients suffering from chronic diseases (e.g., cancer). Numerous conditions can promote skeletal muscle wasting, including several chronic diseases, cancer chemotherapy, aging, and prolonged inactivity. Although the mechanisms responsible for this loss of muscle mass is multifactorial, mitochondrial dysfunction is predicted to be a major contributor to muscle wasting in various conditions. This systematic review will highlight the biochemical pathways that have been shown to link mitochondrial dysfunction to skeletal muscle wasting. Importantly, we will discuss the experimental evidence that connects mitochondrial dysfunction to muscle wasting in specific diseases (i.e., cancer and sepsis), aging, cancer chemotherapy, and prolonged muscle inactivity (e.g., limb immobilization). Finally, in hopes of stimulating future research, we conclude with a discussion of important future directions for research in the field of muscle wasting.

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