Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.24 (mitogen-activated protein kinase)
 95,810 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The toxic aldehydes acetaldehyde and acrolein were previously suggested to damage skeletal muscle. Several conditions in which exposure to acetaldehyde and acrolein is increased were associated with muscle wasting and dysfunction. These include alcoholic myopathy, renal failure, oxidative stress, and inflammation. A main exogenous source of both acetaldehyde and acrolein is cigarette smoking, which was previously associated with increased muscle catabolism. Recently, we have shown that exposure of skeletal myotubes to cigarette smoke stimulated muscle catabolism via increased oxidative stress, activation of p38 MAPK, and upregulation of muscle-specific E3 ubiquitin ligases. In this study, we aimed to investigate the effects of acetaldehyde and acrolein on catabolism of skeletal muscle. Skeletal myotubes differentiated from the C2 myoblast cell line were exposed to acetaldehyde or acrolein and their effects on signaling pathways related to muscle catabolism were studied. Exposure of myotubes to acetaldehyde did not promote muscle catabolism. However, exposure to acrolein caused increased generation of free radicals, activation of p38 MAPK, upregulation of the muscle-specific E3 ligases atrogin-1 and MuRF1, degradation of myosin heavy chain, and atrophy of myotubes. Inhibition of p38 MAPK by SB203580 abolished acrolein-induced muscle catabolism. Our findings demonstrate that acrolein but not acetaldehyde activates a signaling cascade resulting in muscle catabolism in skeletal myotubes. Although within the limitations of an in vitro study, these findings indicate that acrolein may promote muscle wasting in conditions of increased exposure to this aldehyde.
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PMID:The effects of acetaldehyde and acrolein on muscle catabolism in C2 myotubes. 2379 74

Long-term abuse of alcohol results in chronic alcoholic myopathy which is associated with increased oxidative stress. Ginkgo biloba extract (EGB) is widely used as a therapeutic agent to treat certain cardiovascular and neurological disorders. Although EGB is known to possess antioxidant functions and potent cytoprotective effects, its protective mechanism on alcohol-induced oxidative damage in C2C12 myoblasts remains unclear. In this study, we investigated the cytoprotective mechanisms of EGB against alcohol-derived oxidative stress in mouse C2C12 myoblasts. Challenge with alcohol (100mM) caused an increase in intracellular reactive oxygen species in mouse C2C12 myoblasts, which was not alleviated by treatment with EGB. These results indicate that EGB does not seem to act as an ROS scavenger in this experimental model. Additionally, EGB produced activation of ERK and JNK [two major mitogen-activated protein kinases (MAPKs)], an increase in the nuclear level of nuclear factor erythroid-2-related factor 2 (Nrf2) and upregulation of heme oxygenase-1 (HO-1, a stress-responsive protein with antioxidant function). Pretreatment with inhibitors of MAPKs PD98059 (a specific inhibitor of ERK), SP600125 (a specific inhibitor of JNK) abolished both EGB-induced Nrf2 nuclear translocation and HO-1 up-regulation. We conclude that EGB confers cytoprotective effects from oxidative stress induced by alcohol in mouse C2C12 myoblasts depend on transcriptional upregulation of HO-1 by EGB via the MAPKs/Nrf2 pathway.
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PMID:Transcriptional upregulation centra of HO-1 by EGB via the MAPKs/Nrf2 pathway in mouse C2C12 myoblasts. 2544 24