scholarly journals Transcriptomic analysis of the development of skeletal muscle atrophy in cancer-cachexia in tumor-bearing mice

2018 ◽  
Vol 50 (12) ◽  
pp. 1071-1082 ◽  
Author(s):  
Thomas A. Blackwell ◽  
Igor Cervenka ◽  
Bhuwan Khatri ◽  
Jacob L. Brown ◽  
Megan E. Rosa-Caldwell ◽  
...  
Keyword(s):  
Time Course ◽  
Gastrocnemius Muscle ◽  
Cancer Cachexia ◽  
Muscle Wasting ◽  
Global Gene Expression ◽  
Skeletal Muscle Atrophy ◽  
Cytoskeletal Structure ◽  
Protein Ubiquitination ◽  
Global Gene Expression Analysis ◽  
Cellular Pathways

Cancer-cachexia (CC) is a wasting condition directly responsible for 20–40% of cancer-related deaths. The mechanisms controlling development of CC-induced muscle wasting are not fully elucidated. Most investigations focus on the postcachectic state and do not examine progression of the condition. We recently demonstrated mitochondrial degenerations precede muscle wasting in time course progression of CC. However, the extent of muscle perturbations before wasting in CC is unknown. Therefore, we performed global gene expression analysis in CC-induced muscle wasting to enhance understanding of intramuscular perturbations across the development of CC. Lewis lung carcinoma (LLC) was injected into the hind-flank of C57BL6/J mice at 8 wk of age with tumor allowed to develop for 1, 2, 3, or 4 wk and compared with PBS-injected control. Muscle wasting was evident at 4 wk LLC. RNA sequencing of gastrocnemius muscle samples showed widespread alterations in LLC compared with PBS animals with largest differences seen in 4 wk LLC, suggesting extensive transcriptomic alterations concurrent to muscle wasting. Commonly altered pathways included: mitochondrial dysfunction and protein ubiquitination, along with other less studied processes in this condition regulating transcription/translation and cytoskeletal structure. Current findings present novel evidence of transcriptomic shifts and altered cellular pathways in CC-induced muscle wasting.

scholarly journals Exercise as an anti-inflammatory therapy for cancer cachexia: a focus on interleukin-6 regulation

2020 ◽  
Vol 318 (2) ◽  
pp. R296-R310 ◽  
Author(s):  
Hélène N. Daou
Keyword(s):  
Skeletal Muscle ◽  
Systemic Inflammation ◽  
Cancer Cachexia ◽  
Muscle Wasting ◽  
Skeletal Muscle Atrophy ◽  
Ampk Signaling ◽  
Skeletal Muscle Wasting ◽  
Skeletal Muscle Loss ◽  
Anti Inflammatory ◽  
Tumor Growth And Metastasis

Cancer cachexia is a complicated disorder of extreme, progressive skeletal muscle wasting. It is directed by metabolic alterations and systemic inflammation dysregulation. Numerous studies have demonstrated that increased systemic inflammation promotes this type of cachexia and have suggested that cytokines are implicated in the skeletal muscle loss. Exercise is firmly established as an anti-inflammatory therapy that can attenuate or even reverse the process of muscle wasting in cancer cachexia. The interleukin IL-6 is generally considered to be a key player in the development of the microenvironment of malignancy; it promotes tumor growth and metastasis by acting as a bridge between chronic inflammation and cancerous tissue and it also induces skeletal muscle atrophy and protein breakdown. Paradoxically, a beneficial role for IL-6 has also been identified recently, and that is its status as a “founding member” of the myokine class of proteins. Skeletal muscle is an important source of circulating IL-6 in people who participate in exercise training. IL-6 acts as an anti-inflammatory myokine by inhibiting TNFα and improving glucose uptake through the stimulation of AMPK signaling. This review discusses the action of IL-6 in skeletal muscle tissue dysfunction and the role of IL-6 as an “exercise factor” that modulates the immune system. This review also sheds light on the main considerations related to the treatment of muscle wasting in cancer cachexia.

scholarly journals Time Course Global Gene Expression Analysis of an In VivoCandidaBiofilm

2009 ◽  
Vol 200 (2) ◽  
pp. 307-313 ◽  
Author(s):  
Jeniel E. Nett ◽  
Alexander J. Lepak ◽  
Karen Marchillo ◽  
David R. Andes
Keyword(s):  
Gene Expression ◽  
Expression Analysis ◽  
Time Course ◽  
Gene Expression Analysis ◽  
Global Gene Expression ◽  
Global Gene Expression Analysis

scholarly journals Muscle oxidative capacity during IL-6-dependent cancer cachexia

2011 ◽  
Vol 300 (2) ◽  
pp. R201-R211 ◽  
Author(s):  
James P. White ◽  
Kristen A. Baltgalvis ◽  
Melissa J. Puppa ◽  
Shuichi Sato ◽  
John W. Baynes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cytochrome C ◽  
Muscle Mass ◽  
Gastrocnemius Muscle ◽  
Cancer Cachexia ◽  
Muscle Wasting ◽  
Muscle Protein ◽  
Oxidative Capacity ◽  
Muscle Oxidative Capacity ◽  
Markers Of Oxidative Stress

Many diseases are associated with catabolic conditions that induce skeletal muscle wasting. These various catabolic states may have similar and distinct mechanisms for inducing muscle protein loss. Mechanisms related to muscle wasting may also be related to muscle metabolism since glycolytic muscle fibers have greater wasting susceptibility with several diseases. The purpose of this study was to determine the relationship between muscle oxidative capacity and muscle mass loss in red and white hindlimb muscles during cancer cachexia development in the Apc Min/+ mouse. Gastrocnemius and soleus muscles were excised from Apc Min/+ mice at 20 wk of age. The gastrocnemius muscle was partitioned into red and white portions. Body mass (−20%), gastrocnemius muscle mass (−41%), soleus muscle mass (−34%), and epididymal fat pad (−100%) were significantly reduced in severely cachectic mice ( n = 8) compared with mildly cachectic mice ( n = 6). Circulating IL-6 was fivefold higher in severely cachectic mice. Cachexia significantly reduced the mitochondrial DNA-to-nuclear DNA ratio in both red and white portions of the gastrocnemius. Cytochrome c and cytochrome- c oxidase complex subunit IV (Cox IV) protein were reduced in all three muscles with severe cachexia. Changes in muscle oxidative capacity were not associated with altered myosin heavy chain expression. PGC-1α expression was suppressed by cachexia in the red and white gastrocnemius and soleus muscles. Cachexia reduced Mfn1 and Mfn2 mRNA expression and markers of oxidative stress, while Fis1 mRNA was increased by cachexia in all muscle types. Muscle oxidative capacity, mitochondria dynamics, and markers of oxidative stress are reduced in both oxidative and glycolytic muscle with severe wasting that is associated with increased circulating IL-6 levels.

scholarly journals Lactate administration increases mRNA expression of PGC-1α and UCP3 in mouse skeletal muscle

2016 ◽  
Vol 41 (6) ◽  
pp. 695-698 ◽  
Author(s):  
Yu Kitaoka ◽  
Kohei Takeda ◽  
Yuki Tamura ◽  
Hideo Hatta
Keyword(s):  
Skeletal Muscle ◽  
Gene Expression Analysis ◽  
Gastrocnemius Muscle ◽  
Potential Role ◽  
Quantitative Polymerase Chain Reaction ◽  
Global Gene Expression ◽  
Signalling Molecule ◽  
Global Gene Expression Analysis ◽  
Polymerase Chain

To examine the potential role of lactate as a signalling molecule in skeletal muscle, we performed global gene expression analysis of the mouse gastrocnemius muscle, 3 h after lactate administration using the Affymetrix GeneChip system (Affymetrix, Santa Clara, Calif., USA). Among the top 15 genes with the largest fold change, increased expression of Ppargc1a, Pdk4, and Ucp3 was confirmed using real-time quantitative polymerase chain reaction. Our findings suggest that lactate serves as a signal for upregulating genes related to mitochondrial function.

scholarly journals Global gene expression analysis of the Myxococcus xanthus developmental time course

Genomics ◽  
2021 ◽  
Vol 113 (1) ◽  
pp. 120-134
Author(s):  
Gaurav Sharma ◽  
Andrew I. Yao ◽  
Gregory T. Smaldone ◽  
Jennifer Liang ◽  
Matt Long ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Analysis ◽  
Time Course ◽  
Gene Expression Analysis ◽  
Myxococcus Xanthus ◽  
Global Gene Expression ◽  
Developmental Time ◽  
Global Gene Expression Analysis

scholarly journals Sex Differences in Cancer Cachexia

2020 ◽  
Vol 18 (6) ◽  
pp. 646-654
Author(s):  
Xiaoling Zhong ◽  
Teresa A. Zimmers
Keyword(s):  
Weight Loss ◽  
Sex Differences ◽  
Cancer Patients ◽  
Cancer Cachexia ◽  
Muscle Wasting ◽  
Fiber Type ◽  
Global Gene Expression ◽  
Skeletal Muscle Wasting ◽  
Progressive Weight Loss ◽  
And Function

Abstract Purpose of Review Cachexia, a feature of cancer and other chronic diseases, is marked by progressive weight loss and skeletal muscle wasting. This review aims to highlight the sex differences in manifestations of cancer cachexia in patients, rodent models, and our current understanding of the potential mechanisms accounting for these differences. Recent Findings Male cancer patients generally have higher prevalence of cachexia, greater weight loss or muscle wasting, and worse outcomes compared with female cancer patients. Knowledge is increasing about sex differences in muscle fiber type and function, mitochondrial metabolism, global gene expression and signaling pathways, and regulatory mechanisms at the levels of sex chromosomes vs. sex hormones; however, it is largely undetermined how such sex differences directly affect the susceptibility to stressors leading to muscle wasting in cancer cachexia. Summary Few studies have investigated basic mechanisms underlying sex differences in cancer cachexia. A better understanding of sex differences would improve cachexia treatment in both sexes.

scholarly journals Role of myokines and osteokines in cancer cachexia

2021 ◽  
pp. 153537022110092
Author(s):  
Fabrizio Pin ◽  
Lynda F Bonewald ◽  
Andrea Bonetto
Keyword(s):  
Cancer Cachexia ◽  
Muscle Wasting ◽  
Skeletal Muscle Atrophy ◽  
Lipid Mediator ◽  
Promising Strategy ◽  
Different Types ◽  
Ultimate Cause ◽  
Endocrine Factors ◽  
Shed Light

Cancer-induced muscle wasting, i.e. cachexia, is associated with different types of cancer such as pancreatic, colorectal, lung, liver, gastric and esophageal. Cachexia affects prognosis and survival in cancer, and it is estimated that it will be the ultimate cause of death for up to 30% of cancer patients. Musculoskeletal alterations are known hallmarks of cancer cachexia, with skeletal muscle atrophy and weakness as the most studied. Recent evidence has shed light on the presence of bone loss in cachectic patients, even in the absence of bone-metastatic disease. In particular, we and others have shown that muscle and bone communicate by exchanging paracrine and endocrine factors, known as myokines and osteokines. This review will focus on describing the role of the most studied myokines, such as myostatin, irisin, the muscle metabolite β-aminoisobutyric acid, BAIBA, and IL-6, and osteokines, including TGF-β, osteocalcin, sclerostin, RANKL, PTHrP, FGF23, and the lipid mediator, PGE2 during cancer-induced cachexia. The interplay of muscle and bone factors, together with tumor-derived soluble factors, characterizes a complex clinical scenario in which musculoskeletal alterations are amongst the most debilitating features. Understanding and targeting the “secretome” of cachectic patients will likely represent a promising strategy to preserve bone and muscle during cancer cachexia thereby enhancing recovery.

scholarly journals Targeted ablation of TRAF6 inhibits skeletal muscle wasting in mice

2010 ◽  
Vol 191 (7) ◽  
pp. 1395-1411 ◽  
Author(s):  
Pradyut K. Paul ◽  
Sanjay K. Gupta ◽  
Shephali Bhatnagar ◽  
Siva K. Panguluri ◽  
Bryant G. Darnay ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Cancer Cachexia ◽  
Muscle Wasting ◽  
Adaptor Protein ◽  
Adenosine Monophosphate ◽  
Nuclear Factor Κb ◽  
Mitogen Activated Protein Kinase ◽  
Skeletal Muscle Atrophy ◽  
Skeletal Muscle Wasting

Skeletal muscle wasting is a major human morbidity, and contributes to mortality in a variety of clinical settings, including denervation and cancer cachexia. In this study, we demonstrate that the expression level and autoubiquitination of tumor necrosis factor (α) receptor adaptor protein 6 (TRAF6), a protein involved in receptor-mediated activation of several signaling pathways, is enhanced in skeletal muscle during atrophy. Skeletal muscle–restricted depletion of TRAF6 rescues myofibril degradation and preserves muscle fiber size and strength upon denervation. TRAF6 mediates the activation of JNK1/2, p38 mitogen-activated protein kinase, adenosine monophosphate–activated protein kinase, and nuclear factor κB, and induces the expression of muscle-specific E3 ubiquitin ligases and autophagy-related molecules in skeletal muscle upon denervation. Inhibition of TRAF6 also preserves the orderly pattern of intermyofibrillar and subsarcolemmal mitochondria in denervated muscle. Moreover, depletion of TRAF6 prevents cancer cachexia in an experimental mouse model. This study unveils a novel mechanism of skeletal muscle atrophy and suggests that TRAF6 is an important therapeutic target to prevent skeletal muscle wasting.

scholarly journals Global Gene Expression Analysis during Germination in the Chytridiomycete Blastocladiella emersonii

2008 ◽  
Vol 8 (2) ◽  
pp. 170-180 ◽  
Author(s):  
Silvia M. Salem-Izacc ◽  
Tie Koide ◽  
Ricardo Z. N. Vêncio ◽  
Suely L. Gomes
Keyword(s):  
Cell Growth ◽  
Nutrient Medium ◽  
Time Course ◽  
Morphological Changes ◽  
Protein Biosynthesis ◽  
Cell Cycle Control ◽  
Global Gene Expression ◽  
Global Gene Expression Analysis ◽  
Blastocladiella Emersonii ◽  
Positive Effect

ABSTRACT Blastocladiella emersonii is an aquatic fungus of the Chytridiomycete class. During germination, the zoospore, a motile nongrowing cell, goes through a cascade of morphological changes that culminates with its differentiation into the germling cell, capable of coenocytic vegetative growth. Transcriptome analyses of B. emersonii cells were carried out during germination induced under various environmental conditions. Microarray data analyzing 3,563 distinct B. emersonii genes revealed that 26% of them are differentially expressed during germination in nutrient medium at at least one of the time points investigated. Over 500 genes are upregulated during the time course of germination under those conditions, most being related to cell growth, including genes involved in protein biosynthesis, DNA transcription, energetic metabolism, carbohydrate and oligopeptide transport, and cell cycle control. On the other hand, several transcripts stored in the zoospores are downregulated during germination in nutrient medium, such as genes involved in signal transduction, amino acid transport, and chromosome organization. In addition, germination induced in the presence of nutrients was compared with that triggered either by adenine or potassium ions in inorganic salt solution. Several genes involved in cell growth, induced during germination in nutrient medium, do not show increased expression when B. emersonii zoospores germinate in inorganic solution, suggesting that nutrients exert a positive effect on gene transcription. The transcriptome data also revealed that most genes involved in cell signaling show the same expression pattern irrespective of the initial germination stimulus.

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