Muscle wasting and the temporal gene expression pattern in a novel rat intensive care unit model
<p>Abstract</p> <p>Background</p> <p>Acute quadriplegic myopathy (AQM) or critical illness myopathy (CIM) is frequently observed in intensive care unit (ICU) patients. To elucidate duration-dependent effects of the ICU intervention on molecular and functional networks t...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2011-12-01
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| Series: | BMC Genomics |
| Online Access: | http://www.biomedcentral.com/1471-2164/12/602 |
| _version_ | 1819033147965177856 |
|---|---|
| author | Llano-Diez Monica Gustafson Ann-Marie Olsson Carl Goransson Hanna Larsson Lars |
| author_facet | Llano-Diez Monica Gustafson Ann-Marie Olsson Carl Goransson Hanna Larsson Lars |
| author_sort | Llano-Diez Monica |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Acute quadriplegic myopathy (AQM) or critical illness myopathy (CIM) is frequently observed in intensive care unit (ICU) patients. To elucidate duration-dependent effects of the ICU intervention on molecular and functional networks that control the muscle wasting and weakness associated with AQM, a gene expression profile was analyzed at time points varying from 6 hours to 14 days in a unique experimental rat model mimicking ICU conditions, i.e., post-synaptically paralyzed, mechanically ventilated and extensively monitored animals.</p> <p>Results</p> <p>During the observation period, 1583 genes were significantly up- or down-regulated by factors of two or greater. A significant temporal gene expression pattern was constructed at short (6 h-4 days), intermediate (5-8 days) and long (9-14 days) durations. A striking early and maintained up-regulation (6 h-14d) of muscle atrogenes (muscle ring-finger 1/tripartite motif-containing 63 and F-box protein 32/atrogin-1) was observed, followed by an up-regulation of the proteolytic systems at intermediate and long durations (5-14d). Oxidative stress response genes and genes that take part in amino acid catabolism, cell cycle arrest, apoptosis, muscle development, and protein synthesis together with myogenic factors were significantly up-regulated from 5 to 14 days. At 9-14 d, genes involved in immune response and the caspase cascade were up-regulated. At 5-14d, genes related to contractile (myosin heavy chain and myosin binding protein C), regulatory (troponin, tropomyosin), developmental, caveolin-3, extracellular matrix, glycolysis/gluconeogenesis, cytoskeleton/sarcomere regulation and mitochondrial proteins were down-regulated. An activation of genes related to muscle growth and new muscle fiber formation (increase of myogenic factors and JunB and down-regulation of myostatin) and up-regulation of genes that code protein synthesis and translation factors were found from 5 to 14 days.</p> <p>Conclusions</p> <p>Novel temporal patterns of gene expression have been uncovered, suggesting a unique, coordinated and highly complex mechanism underlying the muscle wasting associated with AQM in ICU patients and providing new target genes and avenues for intervention studies.</p> |
| first_indexed | 2024-12-21T07:13:13Z |
| format | Article |
| id | doaj.art-9d2b455e4cb54eaea305e181b970b595 |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-12-21T07:13:13Z |
| publishDate | 2011-12-01 |
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| series | BMC Genomics |
| spelling | doaj.art-9d2b455e4cb54eaea305e181b970b5952022-12-21T19:11:55ZengBMCBMC Genomics1471-21642011-12-0112160210.1186/1471-2164-12-602Muscle wasting and the temporal gene expression pattern in a novel rat intensive care unit modelLlano-Diez MonicaGustafson Ann-MarieOlsson CarlGoransson HannaLarsson Lars<p>Abstract</p> <p>Background</p> <p>Acute quadriplegic myopathy (AQM) or critical illness myopathy (CIM) is frequently observed in intensive care unit (ICU) patients. To elucidate duration-dependent effects of the ICU intervention on molecular and functional networks that control the muscle wasting and weakness associated with AQM, a gene expression profile was analyzed at time points varying from 6 hours to 14 days in a unique experimental rat model mimicking ICU conditions, i.e., post-synaptically paralyzed, mechanically ventilated and extensively monitored animals.</p> <p>Results</p> <p>During the observation period, 1583 genes were significantly up- or down-regulated by factors of two or greater. A significant temporal gene expression pattern was constructed at short (6 h-4 days), intermediate (5-8 days) and long (9-14 days) durations. A striking early and maintained up-regulation (6 h-14d) of muscle atrogenes (muscle ring-finger 1/tripartite motif-containing 63 and F-box protein 32/atrogin-1) was observed, followed by an up-regulation of the proteolytic systems at intermediate and long durations (5-14d). Oxidative stress response genes and genes that take part in amino acid catabolism, cell cycle arrest, apoptosis, muscle development, and protein synthesis together with myogenic factors were significantly up-regulated from 5 to 14 days. At 9-14 d, genes involved in immune response and the caspase cascade were up-regulated. At 5-14d, genes related to contractile (myosin heavy chain and myosin binding protein C), regulatory (troponin, tropomyosin), developmental, caveolin-3, extracellular matrix, glycolysis/gluconeogenesis, cytoskeleton/sarcomere regulation and mitochondrial proteins were down-regulated. An activation of genes related to muscle growth and new muscle fiber formation (increase of myogenic factors and JunB and down-regulation of myostatin) and up-regulation of genes that code protein synthesis and translation factors were found from 5 to 14 days.</p> <p>Conclusions</p> <p>Novel temporal patterns of gene expression have been uncovered, suggesting a unique, coordinated and highly complex mechanism underlying the muscle wasting associated with AQM in ICU patients and providing new target genes and avenues for intervention studies.</p>http://www.biomedcentral.com/1471-2164/12/602 |
| spellingShingle | Llano-Diez Monica Gustafson Ann-Marie Olsson Carl Goransson Hanna Larsson Lars Muscle wasting and the temporal gene expression pattern in a novel rat intensive care unit model BMC Genomics |
| title | Muscle wasting and the temporal gene expression pattern in a novel rat intensive care unit model |
| title_full | Muscle wasting and the temporal gene expression pattern in a novel rat intensive care unit model |
| title_fullStr | Muscle wasting and the temporal gene expression pattern in a novel rat intensive care unit model |
| title_full_unstemmed | Muscle wasting and the temporal gene expression pattern in a novel rat intensive care unit model |
| title_short | Muscle wasting and the temporal gene expression pattern in a novel rat intensive care unit model |
| title_sort | muscle wasting and the temporal gene expression pattern in a novel rat intensive care unit model |
| url | http://www.biomedcentral.com/1471-2164/12/602 |
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