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The available chlamydial genome sequences have made it possible to comprehensively analyze host responses to all chlamydial proteins, which is essential for further understanding of chlamydial pathogenesis and development of effective chlamydial vaccines. Microplates arrayed with 156 Chlamydia trachomatis fusion proteins were used to evaluate antibody responses in women urogenitally infected with C. trachomatis. Based on both the antibody recognition frequency and titer, seven chlamydial antigens encoded by open reading frames (ORFs) CT089, CT147, CT226, CT681, CT694, CT795, and CT858, respectively, were identified as relatively immunodominant; six of these are encoded by hypothetical ORFs. Antibody binding to these chlamydial fusion proteins was blocked by C. trachomatis-infected but not by normal HeLa cell lysates or irrelevant bacterial lysates. These results have revealed novel immune-reactive chlamydial antigens, not only indicating that the hypothetical ORF-encoded proteins are expressed during chlamydial infection in humans but also providing the proof of principle that the fusion protein-based approach can be used to profile human immune responses to chlamydial infection at the whole-genome scale.

C ellular oxidative stress is one of the factors responsible for the propagation of liver diseases, such as hepatitis, cirrhosis, and hepatoma. 1 Several primary antioxidant defense systems such as superoxide dismutase (SOD), catalase, glutathione (GSH), and glutathione peroxidase are present intracellularly. These systems scavenge reactive oxygen species (ROS) such as hydrogen peroxide, superoxide, lipid peroxides, and free radicals. Exposure to oxidative stress may, however, deplete the cellular antioxidant capacity. Therefore, other antioxidant defense systems are expected to play an important role in oxidative stress.Liver fatty acid binding protein (L-FABP) is a 14-kd protein found abundantly in the cytoplasm and the nucleus of hepatocytes. 2,3 L-FABP is very likely to be an effective endogenous antioxidant, because it has high affinity and capacity to bind long-chain fatty acid oxidation products. 4,5 Hepatocyte L-FABP concentration could be as high as 0.4 mmol/L, 6 and it contains a large number of reducing amino acid residues (1 cysteine and 7 methionine residues) in its molecular structure. With an accessible volume enclosed by the molecular surface of L-FABP of 28,600 Å 3,7 the concentration of total methionine residues in L-FABP could be as high as approximately 400 mmol/L. Methionine and cysteine amino acids are regarded as cellular scavengers of activated xenobiotics and

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discovered by Ockner et al. in 1972 ( 2 ) and was originally named Z-protein. Since that time, there has been an explosive growth in information regarding the role of L-FABP in cellular homeostasis. While FABPs are present in many tissues, such as heart, brain, intestinal, skin, adipose, muscle, epidermal, ileal, myelin, and testis, L-FABP is found in abundance in hepatocytes where it accounts for ‫ف‬ 2% of the total cellular protein. Although L-FABP is abundant in the liver, it also is present in tissues such as murine alveolar macrophages ( 3 ), kidney ( 4 ), and intestine ( 5 ).L-FABP is made up of 127 amino acids that compose 10 antiparallel ␤ -strands. These stands are organized into two fi ve-stranded ␤ -sheets and two ␣ -helices. The two ␣ -helices are hypothesized to function as a portal that controls entry and release of ligands from the binding pocket created by the ␤ -strands ( 6 ). A large interior water-fi lled cavity forms the confi nes of the ␤ -strands, which serve as the hydrophobic ligand-binding site. L-FABP is able to bind and translocate many lipophilic substrates throughout the cytosol. Some of these substrates include long-chain fatty acids ( 7-9 ), bile acids ( 10 ), eicosanoids ( 11 ), and hypolipidemic drugs ( 12 ). Transfer of these ligands from L-FABP to membranes is thought to occur by a diffusive process; i.e., the ligand fi rst dissociates from the binding pocket and then diffuses to its site of action, while transfer of ligands from other FABPs, such as I-FABP, is thought to occur by a direct collisional interaction ( 13 ). It seems that L-FABP also plays a role in transferring bound ligands into the nucleus. These ligands could activate the peroxisome proliferator-activated receptor ␣ nuclear receptors and

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Mizunoya W, Upadhaya R, Burczynski FJ, Wang G, Anderson JE. Nitric oxide donors improve prednisone effects on muscular dystrophy in the mdx mouse diaphragm. Am J Physiol Cell Physiol 300: C1065-C1077, 2011. First published January 26, 2011 doi:10.1152/ajpcell.00482.2010.-In Duchenne muscular dystrophy (DMD), palliative glucocorticoid therapy can produce myopathy or calcification. Since increased nitric oxide synthase activity in dystrophic mice promotes regeneration, the outcome of two nitric oxide (NO) donor drugs, MyoNovin (M) and isosorbide dinitrate (I), on the effectiveness of the anti-inflammatory drug prednisone (P) in alleviating progression of dystrophy was tested. Dystrophic mdx mice were treated (18 days) as controls or with an NO donor Ϯ P. Fiber permeability and DNA synthesis were labeled by Evans blue dye (EBD) and bromodeoxyuridine uptake, respectively. P decreased body weight gain, M increased quadriceps mass, and I increased heart mass. P increased fiber permeability (%EBDϩ fibers) and calcification in diaphragm. Treatment with NO donors ϩ P (MϩP, IϩP) reduced %EBDϩ fibers and calcification vs. P alone. %EBDϩ fibers in MϩP diaphragm did not differ from control. NO donor treatment reduced proliferation and the population of c-metϩ cells and accelerated fiber regeneration. Concurrent with P, NO donor treatment suppressed two important detrimental effects of P in mice, possibly by accelerating regeneration, rebalancing satellite cell quiescence and activation in dystrophy, and/or increasing perfusion. Results suggest that NO donors could improve current therapy for DMD.Duchenne muscular dystrophy; skeletal muscle; satellite cells; glucocorticoid MUSCULAR DYSTROPHIES are lethal genetic muscle diseases, and the most common form, Duchenne muscular dystrophy (DMD), is caused by mutation in the dystrophin gene (37). Absence of dystrophin from the cytoskeleton in DMD fibers leads to disruption of the sarcolemma by mechanical stress or exercise and progressive muscle weakness and wasting (20,27,56,69). Investigations of possible therapeutic interventions using the mdx mouse model of DMD have examined gene therapy by viral delivery of full-length dystrophin (28) or microdystrophin (97), stem (satellite) cell transplantation (40), and read-through (91) or exon-skipping approaches (2, 55, 93) to restore dystrophin expression. As these investigations are ongoing, pharmacological treatment with glucocorticoids remains the current "gold standard" therapy in DMD.Treatment with prednisone promotes a palliative reduction in inflammation and delays disease progression (57, 58) in DMD. In DMD patients and mdx mice, prednisone and deflazacort reduce the secondary inflammation that extends muscle fiber necrosis outside the region of primary damage that is caused by exercise-induced membrane breaks or eccentric contraction (25, 63). In addition, deflazacort also upregulates the calcineurin/nuclear factor of activated T cells (NFAT) pathway activity, which counteracts the muscle-specific activation of JNK1 that damages...