Cell adhesion is essential to cell motility and tissue integrity and is regulated by the Integrin family of transmembrane receptors. Integrin binds to ligand extracellularly and provide anchor to the intracellular cytoskeleton via adhesion scaffolding proteins. In order to link cell to the surrounding matrix Integrin needs to be activated. Intracellular activation signals induce perturbations in Integrin cytoplasmic domain that are translated into a conformational change in extracellular region for high affinity ligand binding. Integrin engagement by matrix, in turn, triggers the assembly of adhesion complexes. Such early adhesions promote cytoskeletal organization with subsequent contractile activity that exerts forces against initial Integrin-matrix adhesions. In response to force, Integrin strengthens the interaction with matrix through its clustering and successive recruitment of additional adhesion components. These bidirectional regulatory loops mediated by such interactions are largely dependent on the unique function of Integrin adhesion components. / We demonstrate a novel role for the PDZ/LIM domain protein Zasp as a core component of Integrin adhesions. Specifically, Zasp colocalizes with Integrins at focal adhesion in cultured cells and myotendinous junctions in Drosophila embryos. In both cases elimination of Zasp modifies Integrin function causing consequently defects in cell spreading and muscle attachment. Zasp supports Integrin adhesion to the extracellular matrix that is required to withstand tensile forces exerted during cell spreading and muscle contraction. Furthermore, we found that the distribution of Zasp in muscle Z-lines is essential to orchestrate the cross-linking of alpha-Actinin and Actin filaments. Disruption of Zasp leads to loss of muscle cytoarchitecture, pointing to a larger role for Zasp in sarcomere assembly. Finally, we demonstrate that Zasp, in addition to alpha-Actinin, physically interacts with the Integrin- and Actin-bound cytoskeletal protein Talin. / Collectively, our results point to a dual role for Zasp as a structural scaffold. First it regulates Integrin adhesion to the extracellular matrix by interacting with the head domain of Talin at the myotendinous junctions. Second, Zasp controls sarcomere assembly by tethering the presarcomeric alpha-Actinin component to the tail domain of Talin. Zasp finding as a crucial adhesion component provides further insights on the mechanism underlying Integrin-mediated adhesion.

For the past 45 years, QKI has been studied for its role in the processes of development and central nervous system myelination using the qkv mouse. The presence of a single KH domain and the recent identification of a high-affinity binding site in mRNAs, suggests that it can bind to and regulate mRNAs through processes such as stability, splicing and transport. As a member of the STAR RNA binding family of proteins the QKI isoforms may also be involved in cell signaling pathways. / QKI's involvement in all of these processes, lead us to examine both the protein partners and the mRNA targets of the QKI complex in order to identify potentially new pathways regulated by QKI. In doing so, we identified a novel direct protein-protein interaction with PABP and for the first time described the relocalization of QKI to cytoplasmic granules following oxidative stress. In addition, in vivo mRNA interaction studies were performed and allowed the identification of approximately 100 new mRNA targets in human glioblastoma cells. One of the targets identified was VEGF mRNA. / Another QKI target mRNA is MBP, a major protein component of the myelin sheath and the candidate auto-antigen in multiple sclerosis (MS). In vivo MBP is symmetrically dimethylated on a single arginine residue. To further establish the role of the methylation of MBP in myelination, a methyl-specific antibody and an adenovirus expressing a recombinant protein arginine methyltransferase 5 (PRMT5) was generated. We show that methylated MBP is found in areas of mature myelin and that overexpression of the PRTM5 blocked the differentiation of oligodendrocytes. / Taken together these datas implicate QKI for the first time in the process of human cancer angiogenesis and could explain the vascularization defects observed in some of the qkI mutant mice. In addition, arginine methylation of MBP may prove to have an important role in the process of myelination and in the pathogenesis of demyelination and the autoimmune reaction in diseases such as MS.

No description available.

No description available.

Four studies were conducted to determine the effect of synchronization of protein and starch degradation on nutrient utilization, microbial protein synthesis and milk production in dairy cows. In Experiment 1, five cereal grains and five protein supplements were compared for extent of solubility and degradability of their starch and nitrogen fractions. Results indicated large differences which permitted their ranking from high to low degradability as follows: grains, oats > wheat > barley > corn > milo protein supplements, soybean meal > cottonseed meal, (CSM) > corn gluten meal > brewers dried grains, (BDG) > blood meal. In Experiment 2, the five grains were incubated for varying times in vitro (with added amylase) or in situ to determine rate and extent of degradation of dry matter, crude protein and starch. Results showed that rate of starch degradation followed a similar, but slightly different trend than in trial 1 (wheat > barley > oats > corn > milo). Rates for DM and CP degradation were similar than those for starch. In Experiment 3, high (barley, HS) and low (milo, LS) degradable starch sources were combined with a high (CSM, HP) and a low (BDG, LP) degradable protein sources to formulate four diets; HSHP, HSLP, LSHP and LSLP. Diets were fed to 32 cows, starting two to four weeks postpartum, for a 60-d milk production and digestibility study. Apparent digestibility was calculated using chromium oxide. Organic matter digestibility was higher (P < .05) was found in nutrient output to the small intestine among diets and microbial CP synthesis was higher (P > .05) for barley diets.

by Mo Flora. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1991. / Includes bibliographical references (leaves 168-184). / ACKNOWLEDGEMENT --- p.i / ABSTRACT --- p.ii / TABLE OF CONTENTS --- p.iv / Chapter CHAPTER ONE --- INTRODUCTION / Chapter 1.1 --- Stroke as a major disabling disease --- p.1 / Chapter 1.2 --- Classification of stroke --- p.4 / Chapter 1.3 --- Risk factors attributing to stroke --- p.15 / Chapter 1.4 --- Experimental methods to induce cerebral ischemia --- p.19 / Chapter 1.4.1 --- The establishment of animal models for stroke --- p.21 / Chapter 1.4.2 --- Gerbil as a putative model --- p.25 / Chapter 1.5 --- Mechanisms of focal ischemia damage --- p.30 / Chapter 1.6 --- Potential biochemical markers for cerebral ischemia --- p.38 / Chapter 1.7 --- Aim of investigation --- p.48 / Chapter CHAPTER TWO --- MATERIALS AND METHODS / Chapter 2.1 --- Common chemicals --- p.49 / Chapter 2.2 --- Common bench solutions --- p.52 / Chapter 2.3 --- Animals / Chapter 2.3.1 --- Gerbils --- p.52 / Chapter 2.3.2 --- Rabbit --- p.53 / Chapter 2.4 --- Establishment of an animal model / Chapter 2.4.1 --- Surgical methods for common carotid artery (CCA) ligation --- p.54 / Chapter 2.5 --- Methods to determine stroke conditions of gerbils / Chapter 2.5.1 --- Ocular fundus examination --- p.56 / Chapter 2.5.2 --- Stroke index --- p.56 / Chapter 2.5.3 --- Inclined plane method --- p.59 / Chapter 2.6 --- Preparation of gerbil brain for subsequent analysis / Chapter 2.6.1 --- Preparation of gerbil brain slices --- p.61 / Chapter 2.6.2 --- "2,3,5-triphenytetrazolium chloride (TTC) for quantitative staining of brain slices" --- p.61 / Chapter 2.6.3 --- Preparation of normal and stroke gerbil brain extract --- p.62 / Chapter 2.7 --- Polyacrylamide gel electrophoresis (PAGE) using a discontinuous buffer system / Chapter 2.7.1 --- Stock reagents --- p.63 / Chapter 2.7.2 --- Separation gel preparation --- p.65 / Chapter 2.7.3 --- Stacking gel preparation --- p.66 / Chapter 2.7.4 --- Electrophoresis conditions --- p.67 / Chapter 2.7.5 --- Staining and destaining --- p.67 / Chapter 2.8 --- Two dimensional slab gel electrophoresis / Chapter 2.8.1 --- Equipment --- p.70 / Chapter 2.8.2 --- Chemical --- p.70 / Chapter 2.8.3 --- Procedure --- p.74 / Chapter 2.9 --- Production of rabbit polyclonal antibodies against isolated stroke protein / Chapter 2.9.1 --- Isolation of stroke protein band from SDS-PAGE slab gel --- p.78 / Chapter 2.9.2 --- Production of anti-stroke protein serum in rabbits --- p.79 / Chapter 2.10 --- Western blotting method / Chapter 2.10.1 --- Reagents --- p.80 / Chapter 2.10.2 --- Procedures --- p.81 / Chapter 2.11 --- Extraction of total cellular RNA by lithium chloride method / Chapter 2.11.1 --- Reagents --- p.83 / Chapter 2.11.2 --- Procedures --- p.84 / Chapter 2.11.3 --- Checking the purity of the extracted RNA --- p.85 / Chapter 2.12 --- Purification of mRNA / Chapter 2.12.1 --- Reagents --- p.85 / Chapter 2.12.2 --- Procedure --- p.86 / Chapter 2.13 --- Verification of purity of mRNA / Chapter 2.13.1 --- Reagents --- p.87 / Chapter 2.13.2 --- Procedure --- p.88 / Chapter 2.14 --- Translation of gerbil brain mRNA in reticulocyte lysates and analysis of its product by SDS PAGE / Chapter 2.14.1 --- Reagents --- p.89 / Chapter 2.14.2 --- Procedures --- p.89 / Chapter CHAPTER THREE --- ESTABLISHMENT OF AN ANIMAL STROKE MODEL / Chapter 3.1 --- Foreword --- p.92 / Chapter 3.2 --- Preliminary studies / Chapter 3.2.1 --- Introduction --- p.92 / Chapter 3.2.2 --- Results --- p.93 / Chapter 3.2.3 --- Discussion --- p.96 / Chapter 3.3 --- Survival rate analysis / Chapter 3.3.1 --- Introduction --- p.97 / Chapter 3.3.2 --- Result --- p.98 / Chapter 3.3.3 --- Discussion --- p.102 / Chapter 3.4 --- Neurologic signs of ischemia / Chapter 3.4.1 --- Introduction --- p.103 / Chapter 3.4.2 --- Result --- p.105 / Chapter 3.4.3 --- Discussion --- p.111 / Chapter 3.5 --- Ocular fundus examination / Chapter 3.5.1 --- Introduction --- p.112 / Chapter 3.5.2 --- Result --- p.114 / Chapter 3.5.3 --- Discussion --- p.116 / Chapter 3.6 --- Inclined plane method / Chapter 3.6.1 --- Introduction --- p.117 / Chapter 3.6.2 --- Result --- p.118 / Chapter 3.6.3 --- Discussion --- p.121 / Chapter 3.7 --- Histologic examination using TTC as staining agent / Chapter 3.7.1 --- Introduction --- p.122 / Chapter 3.7.2 --- Result --- p.124 / Chapter 3.7.3 --- Discussion --- p.129 / Chapter CHAPTER FOUR --- IDENTIFICATION OF ALTERED PROTEIN PATTERN IN THE - BRAINS OF STROKE GERBILS BY ELECTROPHORETIC METHODS / Chapter 4.1 --- Separation of soluble brain extracts by SDS-PAGE analysis / Chapter 4.1.1 --- Introduction --- p.130 / Chapter 4.1.2 --- Result --- p.132 / Chapter 4.1.3 --- Discussion --- p.140 / Chapter 4.2 --- Two dimensional electrophoretic analysis of soluble brain extracts from stroke gerbils / Chapter 4.2.1 --- Introduction --- p.142 / Chapter 4.2.2 --- Result --- p.143 / Chapter 4.2.3 --- Discussion --- p.148 / Chapter CHAPTER FIVE --- ISOLATION OF STROKE-ASSOCIATED PROTEIN FROM BRAINS OF STROKE GERBILS BY IMMUNOCHEMICAL METHOD / Chapter 5.1 --- Introduction --- p.149 / Chapter 5.2 --- Result --- p.151 / Chapter 5.3 --- Discussion --- p.153 / Chapter CHAPTER SIX --- DETECTION OF NEW PROTEIN TRANSLATED FROM MESSENGER RIBONUCLEIC ACID FROM BRAINS OF STROKE GERBIL / Chapter 6.1 --- Introduction / Chapter 6.1.1 --- Extraction of stroke gerbil brain messenger ribonucleic acid --- p.154 / Chapter 6.1.2 --- Translation of mRNA --- p.154 / Chapter 6.2 --- Results / Chapter 6.2.1 --- Yield of total cellular RNA --- p.157 / Chapter 6.2.2 --- Verification of purity of mRNA --- p.157 / Chapter 6.2.3 --- Autoradiographic patterns of translated proteins --- p.159 / Chapter 6.3 --- Discussion --- p.163 / Chapter CHAPTER SEVEN --- GENERAL DISCUSSION --- p.165 / BIBLIOGRAPHY --- p.168

Chu Lai On. / Thesis submitted in: July 2004. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 152-172). / Abstracts in English and Chinese. / Acknowledgements --- p.2 / Abstract --- p.3 / Table of Content --- p.7 / Abbreviations --- p.12 / Naming system for mutant proteins --- p.13 / Abbreviations for amino acid --- p.14 / Chapter Chapter 1 --- Introduction --- p.15 / Chapter 1.1 --- Structure-function relationship of trichosanthin --- p.18 / Chapter 1.2 --- Properties of acidic ribosomal P-proteins --- p.21 / Chapter 1.3 --- Interaction among P-proteins and trichosanthin --- p.25 / Chapter 1.4 --- Properties of eukaryotic elongation factor 2 and interaction with P-proteins --- p.26 / Chapter 1.5 --- "Objectives and strategy of studying the interaction among trichosanthin, P-proteins and eukaryotic elongation 2" --- p.30 / Chapter Chapter 2 --- Materials and Methods --- p.33 / Chapter 2.1 --- General techniques --- p.33 / Chapter 2.1.1 --- Preparation and transformation of Escherichia coli competent cells --- p.33 / Chapter 2.1.2 --- Minipreparation of plasmid DNA using Wizard Plus SV Minipreps DNA purification kit from Promega --- p.34 / Chapter 2.1.3 --- Agarose gel electrophoresis of DNA --- p.36 / Chapter 2.1.4 --- Purification of DNA from agarose gel using Wizard SV Gel and PCR Clean-Up System from Promega --- p.36 / Chapter 2.1.5 --- Polymerase Chain Reaction (PCR) --- p.37 / Chapter 2.1.5.1 --- Basic Protocol --- p.37 / Chapter 2.1.5.2 --- Generation of P2 truncation mutants --- p.38 / Chapter 2.1.5.3 --- Generation of TCS mutants --- p.39 / Chapter 2.1.6 --- Restriction digestion of DNA --- p.41 / Chapter 2.1.7 --- Ligation of DNA fragments --- p.41 / Chapter 2.1.8 --- SDS-polyacrylamide gel electrophoresis (SDS-PAGE) --- p.42 / Chapter 2.1.9 --- Staining of protein in polyacrylamide gel --- p.45 / Chapter 2.2 --- Expression and purification of recombinant proteins --- p.46 / Chapter 2.2.1 --- "Bacterial culture, harvesting and lysis" --- p.46 / Chapter 2.2.2 --- Purification of recombinant TCS and mutants --- p.47 / Chapter 2.2.3 --- Purification of acidic ribosomal protein P2 and mutants --- p.48 / Chapter 2.2.4 --- Purification of MBP-fusion proteins --- p.50 / Chapter 2.3 --- Purification of eEF2 from rat livers --- p.51 / Chapter 2.4 --- In vitro binding assay by NHS-activated Sepharose resin --- p.53 / Chapter 2.4.1 --- Coupling of protein sample to NHS-activated Sepharose resin --- p.53 / Chapter 2.4.2 --- In vitro binding of protein sample to coupled NHS-activated resin --- p.54 / Chapter 2.5 --- Ribosome-inactivated activity assay using rabbit reticulocyte lysate in vitro translation system --- p.55 / Chapter 2.6 --- Circular dichroism (CD)spectrometry --- p.57 / Chapter 2.7 --- Isothermal titration calorimetry (ITC) experiment --- p.57 / Chapter 2.8 --- Surface plasmon resonance (SPR) experiment --- p.58 / Chapter 2.8.1 --- Immobilization of P2 onto aminosilane cuvette --- p.58 / Chapter 2.8.2 --- Interaction between eEF2 and immobilized P2 --- p.60 / Chapter 2.9 --- Preparation of Anti-P antibody --- p.61 / Chapter 2.10 --- Western blotting of protein --- p.62 / Chapter 2.11 --- Reagents and buffer --- p.64 / Chapter 2.11.1 --- Reagents for competent cell preparation --- p.64 / Chapter 2.11.2 --- Nucleic acids electrophoresis buffer --- p.65 / Chapter 2.11.3 --- Media for bacterial culture --- p.66 / Chapter 2.11.4 --- Buffers for TCS purification --- p.67 / Chapter 2.11.5 --- Buffers for eEF2 purification --- p.68 / Chapter 2.11.6 --- Reagents for SDS-PAGE --- p.68 / Chapter 2.11.7 --- Reagents and buffers for Western blot --- p.70 / Chapter 2.11.8 --- Reagents and buffers for coupling sample proteins to NHS-activated Sepharose resin --- p.72 / Chapter 2.11.9 --- Reagents and buffers for in vitro binding assay --- p.72 / Chapter 2.11.10 --- Reagents and Buffers for surface plasmon resonance --- p.72 / Chapter 2.12 --- Sequences of primers --- p.73 / Chapter Chapter 3 --- Interaction between TCS and P2 --- p.80 / Chapter 3.1 --- Introduction --- p.80 / Chapter 3.2 --- Interaction between TCS and P-proteins in rat liver lysate --- p.83 / Chapter 3.3 --- Construction of TCS mutants --- p.85 / Chapter 3.4 --- Expression and purification of TCS mutants --- p.87 / Chapter 3.5 --- Biological assay of TCS mutants --- p.91 / Chapter 3.6 --- Physical interaction of TCS mutants and P2 by surface plasmon resonance (SPR) --- p.94 / Chapter 3.7 --- Discussion --- p.100 / Chapter Chapter 4 --- Mapping the region of P2 that binds TCS and eEF2 --- p.104 / Chapter 4.1 --- Introduction --- p.104 / Chapter 4.2 --- Construction of P2 truncation mutants --- p.106 / Chapter 4.3 --- Expression and purification of P2 truncation mutants --- p.107 / Chapter 4.4 --- Mapping the region of P2 that binds TCS --- p.111 / Chapter 4.4.1 --- Interaction between TCS and P2 mutants by in vitro binding assay --- p.111 / Chapter 4.4.2 --- Interaction study of TCS and P2 mutant by isothermal titration calorimetry (ITC) --- p.116 / Chapter 4.5 --- Mapping the region of P2 that binds eEF2 --- p.120 / Chapter 4.5.1 --- Purification of eEF2 from rat liver --- p.120 / Chapter 4.5.2 --- Physical interaction of P2 and eEF2 by surface plasmon resonance (SPR) --- p.126 / Chapter 4.5.3 --- Interaction between eEF2 and P2 mutants by in vitro binding assay --- p.128 / Chapter 4.6 --- Mapping the C-terminal region of P2 by MBP-fusion proteins --- p.130 / Chapter 4.6.1 --- Construction and purification of MBP-fusion proteins --- p.131 / Chapter 4.6.2 --- "Interaction among eEF2, TCS and MBP-fusion proteins by in vitro binding assay" --- p.133 / Chapter 4.7 --- Discussion --- p.137 / Chapter Chapter 5 --- Effect of C-17 peptide on TCS biological activity --- p.143 / Chapter 5.1 --- Introduction --- p.143 / Chapter 5.2 --- Ribosome-inactivating activity of TCS with C-17 peptide --- p.145 / Chapter 5.3 --- Discussion --- p.147 / Chapter Chapter 6 --- Conclusion and suggestions for future study --- p.149 / References --- p.152 / Appendix --- p.173

Background. B-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi-1) acts as an oncogene in various cancer such as non-small cell lung cancer, colon cancer, gastric cancer, bladder cancer and nasopharyngeal cancer (NPC). / Methods. Immunohistochemistry was performed to evaluate Bmi-1 expression in 252 breast cancer samples. The correlations were analyzed between Bmi-1 expression and clinicopathologic parameters, including age, tumor size, lymph nodal involvement, distant metastasis, clinical stages, hormone receptor (ER, PR) and Human Epidermal Growth Factor Receptor 2 (HER-2). The overall survivals were compared by Kaplan-Meier analysis based on Bmi-1 expression. / Results. Bmi-1 expression was significantly increased in primary cancer tissues than in matched adjacent non-cancerous tissues ( P&lt;0.001). Only 35.9% (14 of 39) of adjacent non-cancerous tissues displayed high expression compared with 72.2% (182 of 252) in primary cancer tissues. Among adjacent non-cancerous tissues, no Bmi-1 staining signal was detected in 30.8% (12 in 39) samples. Only 28.2% (11 in 39) samples showed nucleus staining and the remaining 41.0% (16 in 39) samples exhibited cytoplasm staining. Of those cancer tissues, however, 75.4% (190 in 252) was stained in the nucleus and 24.6% (62 in 252) located in the cytoplasm. The elevated Bmi-1 expression was correlated with advanced clinicopathologic classifications (T, N, M) and clinical stages (P&lt;0.001, respectively). A high level of Bmi-1 expression displayed unfavorable overall survival ( P&lt;0.001). The overall survival rate, assessed by the Kaplan-Meier method, was 85.1% (57 in 67) in low Bmi-1 expression group, whereas it was only 59.9% (103 in 172) in high Bmi-1 expression group. In addition, Bmi-1 serves as a high risk for breast cancer and the relative risk increased almost four fold in patients with high Bmi-1 expression compared with that with low Bmi-1 expression by univariate Cox regression analyses. After the adjustment of the confounding factors, Bmi-1 was still found to predict the poor survival (P=0.042), which indicated Bmi-1 was an independent prognostic factor. The overexpression of Bmi-1 increased the mobility and invasiveness in 76N-TERT and MCF-10A, concurrent EMT-like molecular changes, the stabilization of Snail protein and the activation of Akt/GSK3beta pathway. Consistent with these observations, the repression of Bmi-1 in MDA-MB-435S remarkably attenuated the cellular mobility, invasiveness and transformation, as well as tumorigenesis and spontaneous lung metastases in nude mice. In addition, the repression of Bmi-1 reversed the EMT markers and inhibited the Akt/GSK3beta/Snail pathway. However, ectopic Bmi-1 alone was not able to lead to the phenotype of HMECs. Additionally, discordant mRNA expression levels of Bmi-1 and E-cadherin were detected between primary cancer tissues and matched adjacent non-cancerous tissues. The mRNA level of Bmi-1 was strongly up-regulated in breast cancer tissues compared with paired non-cancerous tissues ( P=0.001), whereas the mRNA level of E-cadherin was markedly down-regulated (P=0.042). Furthermore, there was a converse correlation between Bmi-1 and E-cadherin expression at the transcriptional level ( P=0.041). (Abstract shortened by UMI.) / Guo, Baohong. / Adviser: Kung, Hsiang Fu. / Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 161-183). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Protein wasting is a complication of glucocorticoid (GC) therapy. It causes substantial morbidity and there is no treatment. This thesis investigates the metabolic mechanisms underlying GC-induced protein wasting and the potential for anabolic hormones to reverse protein loss. The models of GC excess were Cushing's syndrome and GC therapy. Whole body protein metabolism was assessed using the leucine turnover technique and body composition by dual-energy X-ray absorptiometry to estimate lean body mass (LBM) and fat mass (FM). As previous studies demonstrated that LBM and FM influenced rates of protein metabolism, the magnitude of body compositional abnormality in Cushing's syndrome was determined. After accounting for the greater FM (30%) and lesser LBM (15%), protein metabolism in Cushing's syndrome was characterised by a significant increase in protein oxidation, an abnormality that leads to irreversible protein loss. Successful treatment of Cushing's syndrome normalised protein oxidation. Studies of the acute and chronic effects of therapeutic GCs revealed a time-dependent effect on protein metabolism. GCs acutely increased protein oxidation. However, the rate of protein oxidation during chronic therapy at a similar dose was not significantly different to untreated control subjects. This time-dependent change suggests that GC-induced stimulation of protein oxidation does not persist and could represent a metabolic adaptation to limit protein loss. This finding contrasts with that in Cushing's syndrome, where protein oxidation is persistently elevated. This difference may represent a dose effect. Studies in GH-deficient subjects revealed that GH induced a fall in protein oxidation that was significantly correlated with a subsequent gain in LBM. This suggests that the anabolic potential of a therapeutic substance can be predicted by its ability to suppress protein oxidation acutely. Finally, the potential for GH and androgens to reverse the metabolic effects of GCs was assessed. A preliminary study in GC users revealed that a GH dose of 0.8 mg/d was effective in reducing protein oxidation. In a subsequent study, the GH-induced reduction in protein oxidation in women on GCs was enhanced by combined treatment with dehydroepiandrosterone, an androgen. In summary, GCs induce protein loss by stimulating protein oxidation. GH reverses this effect and this action is enhanced by coadministration of androgens. GH and androgens may be used therapeutically to prevent protein loss induced by GCs.

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