? Both neural and weight-bearing activities have been shown to be important physiological factors regulating slow skeletal muscle phenotype in the adult animal. While these phenotypic changes have been well characterized, there is not much known about the molecular mechanisms through which neuromuscular activity regulates the slow contractile protein isoform genes. The experiments described in this proposal (competitive supplement forAR43349) will incorporate microarray technology to perform expression profiling for the identification of genes in skeletal muscle that are slow nerve and/or mechanical load dependent. The inclusion of the microarray studies will increase the breadth of the current proposal on the nerve and mechanical load regulation of slow myosin. Work from the array project will likely identify new molecules (transcription factors and kinases) that are critical for the regulation of the slow myosin gene in response to slow innervation and/or mechanical load.
The specific aims of this supplement are use microarrary technology to 1) identify dusters of slow nerve dependent genes and 2) identify common and unique clusters of genes associated with mechanical loading. Based on the experience and previous collaboration between the PI and Co-PI there is high likelihood that bioinformatic analysis of the microaray data will likely identify new nerve and load dependent genes in skeletal muscle and more importantly will provide important information for the expansion of current hypotheses for the molecular mechanisms underlying physiological response of skeletal muscle phenotype. This work has broad application to basic and applied areas of biomedical and health science fields. At the basic science level, new insight will be gained into molecular mechanisms by which slow skeletal muscle phenotype is attained. At the more applied level, because of the common occurrence of muscle regeneration in humans, this study will have wide rehabilitative application for decisions of stimulation/loading paradigms. Muscle regeneration does occur following muscle transplant surgery for correction of facial paralysis; following muscle damage due to mechanical, thermal, or metabolic stress; as well as its association with dystrophic muscle pathologies. ? ? ?
| Srikuea, Ratchakrit; Esser, Karyn A; Pholpramool, Chumpol (2011) Leukaemia inhibitory factor is expressed in rat gastrocnemius muscle after contusion and increases proliferation of rat L6 myoblasts via c-Myc signalling. Clin Exp Pharmacol Physiol 38:501-9 |
