Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In muscular dystrophy (MD) the imbalance between muscle protein synthesis and degradation may be an important factor leading to muscle wasting. The three major pathways of muscle proteolysis identified in skeletal muscle are: the lysosomal cathepsin pathway, the calcium-dependent calpain pathway, and the ATP-dependent ubiquitin pathway. Insulin-like growth factor I (IGF-I) and a high-protein diet (HPD) have been shown to reduce proteolysis in skeletal muscle. We examined the effect of 6 weeks of recombinant human IGF-I (rhIGF-I) alone or in combination with HPD treatment on the proteolytic pathways in skeletal muscle of 129 ReJ dystrophic (dy) mice. (A group of normal (Norm) nondystrophic (129 J) mice were included as controls). Untreated dy mice exhibited increased net proteolysis (P < 0.05), elevated net calpain activity (P < 0.01), and increased ubiquitin levels when compared to control mice (P < 0.05). Our evidence suggests that HPD and rhIGF-I decrease proteolysis in the 129 ReJ dy mouse. This effect appears attributable, at least in part, to reduced calpain-mediated myofibrillar breakdown (P < 0.05) due to decreased calpain autolysis or increased calpastatin levels. In contrast to calpain, cathepsin B activity was increased in HPD and rhIGF-I + HPD-treated dy muscle (P < 0.05) and unaltered in the rhIGF-I treated animals. Levels of free and protein-conjugated ubiquitin were also increased in rhIGF-I, and rhIGF-I + HPD treated dyanimals (P < 0.05). The amelioration of muscle wasting in the 129 ReJ dy model by HPD and/or rhIGF-I may have potential implications in the treatment of human MD.
 ...
PMID:Insulin-like growth factor-I and high protein diet decrease calpain-mediated proteolysis in murine muscular dystrophy. 964 44

Insulin-like growth factor I (IGF-I) is an important growth factor for embryonic development, postnatal growth, tissue repair and maintenance of homeostasis. IGF-I functions and regulations are complex and tissue-specific. IGF-I mediates growth hormone signaling to target tissues during growth, but many IGF-I variants have been discovered, resulting in complex models to describe IGF-I function and regulation. Mechano-growth factor (MGF) is an alternative splicing variant of IGF-I and serves as a local tissue repair factor that responds to changes in physiological conditions or environmental stimuli. MGF expression is significantly increased in muscle, bone and tendon following damage resulting from mechanical stimuli and in the brain and heart following ischemia. MGF has been shown to activate satellite cells in muscle resulting in hypertrophy or regeneration, and functions as a neuroprotectant in brain ischemia. Both expression and processing of this IGF-I variant are tissue specific, but the functional mechanism is poorly understood. MGF and its short derivative have been examined as a potential therapy for muscular dystrophy and cerebral hypoxia-ischemia using experimental animals. Although the unique mode of action of MGF has been identified, the details remain elusive. Here we review the expression and regulation of MGF and the function of this IGF-I isoform in tissue protection.
 ...
PMID:IGF-IEc expression, regulation and biological function in different tissues. 2049