Thus, further work is needed before the increased protein ubiquitination observed here is attributed to MuRF-1 and/or atrogin-1 as well as to precisely define the role of proteasomal pathways in human immobilization-induced muscle atrophy.
To examine the potential role of mTOR in human immobilization-induced muscle atrophy both the levels of total cellular mTOR and phospho-mTOR were measured and no significant change in the former was detected (not shown).
Results using micro-array analysis obtained here support a role for decreased protein synthesis in the later stages of human immobilization-induced muscle atrophy as genes encoding ribosomal subunits, translation initiation and elongation factors, and tRNA synthesizing enzymes were significantly down-regulated in the late (14 D) time-point of immobilization (Table S1, Figure 1B).
In addition, the large cohort used in this study enabled us to map out both early and late transcriptional patterns in human muscle during immobilization.
Together, these findings suggest that signaling through mTOR may decline transiently during the early response of human muscle to immobilization and may contribute to decreased mitochondrial gene expression, possibly through interactions with PGC-1α [42].
Yet, several human studies with immobilization have casted doubt on this hypothesis because they observed decreases in the rates of protein synthesis and muscle mass in the absence of changes in mTOR signaling (de Boer et al., 2007; Marimuthu et al., 2011).
Bidarra, S. J., Barrias, C. C., Barbosa, M. A., Soares, R. & Granja, P. L. Immobilization of human mesenchymal stem cells within RGD-grafted alginate microspheres and assessment of their angiogenic potential.
We report on a methodology for the covalent immobilization of human CYP2E1 and glucose-6-phosphate dehydrogenase (G6PD) in the microchannels of porous alumina membranes (60 μm thickness) for the purpose of xenobiotic metabolic's studies.
Therefore, in this study, polymer poly ethylene terephthalate) (PET) films were surface modified by graft polymerization of acrylic acid, to subsequently allow collagen (types I and III) immobilization and human smooth muscle cell expansion.
In addition, future experiments focused on evaluating cellular proteasomal pathways by directly measuring the activity of Ub-proteasome, calpains, and caspases are vital to understanding the role of these systems in human muscle atrophy following immobilization.
