Enzyme replacement prevents neonatal death, liver damage, and osteoporosis in murine homocystinuria [Research]
In this study, newborn CBS-knockout (KO) mice were treated with recombinant polyethyleneglycolylated human truncated CBS (PEG-CBS). Full survival of the treated KO mice, along with a positive impact on metabolite levels in plasma, liver, brain, and kidneys, was observed. The PEG-CBS treatment prevented an otherwise fatal liver disease characterized by steatosis, death of hepatocytes, and ultrastructural abnormalities of endoplasmic reticulum and mitochondria. Furthermore, treatment of the KO mice for 5 mo maintained the plasma metabolite balance and completely prevented osteoporosis and changes in body composition that cha...
Source: FASEB Journal - November 30, 2017 Category: Biology Authors: Majtan, T., Hulkova, H., Park, I., Krijt, J., Kozich, V., Bublil, E. M., Kraus, J. P. Tags: Research Source Type: research
Dynamic proteome profiling of individual proteins in human skeletal muscle after a high-fat diet and resistance exercise [Research]
It is generally accepted that muscle adaptation to resistance exercise (REX) training is underpinned by contraction-induced, increased rates of protein synthesis and dietary protein availability. By using dynamic proteome profiling (DPP), we investigated the contribution of both synthesis and breakdown to changes in abundance on a protein-by-protein basis in human skeletal muscle. Age-matched, overweight males consumed 9 d of a high-fat, low-carbohydrate diet during which time they either undertook 3 sessions of REX or performed no exercise. Precursor enrichment and the rate of incorporation of deuterium oxide into newly s...
Source: FASEB Journal - November 30, 2017 Category: Biology Authors: Camera, D. M., Burniston, J. G., Pogson, M. A., Smiles, W. J., Hawley, J. A. Tags: Research Source Type: research
Effects of spaceflight on the muscles of the murine shoulder [Research]
Mechanical loading is necessary for the development and maintenance of the musculoskeletal system. Removal of loading via microgravity, paralysis, or bed rest leads to rapid loss of muscle mass and function; however, the molecular mechanisms that lead to these changes are largely unknown, particularly for the spaceflight (SF) microgravity environment. Furthermore, few studies have explored these effects on the shoulder, a dynamically stabilized joint with a large range of motion; therefore, we examined the effects of microgravity on mouse shoulder muscles for the 15-d Space Transportation System (STS)-131, 13-d STS-135, an...
Source: FASEB Journal - November 30, 2017 Category: Biology Authors: Shen, H., Lim, C., Schwartz, A. G., Andreev-Andrievskiy, A., Deymier, A. C., Thomopoulos, S. Tags: Research Source Type: research
6-Methoxyethylamino-numonafide inhibits hepatocellular carcinoma xenograft growth as a single agent and in combination with sorafenib [Research]
Hepatocellular carcinoma (HCC) is the third leading form of cancer worldwide, and its incidence is increasing rapidly in the United States, tripling over the past 3 decades. The current chemotherapeutic strategies against localized and metastatic HCC are ineffective. Here we report that 6-methoxyethylamino-numonafide (MEAN) is a potent growth inhibitor of murine xenografts of 2 human HCC cell lines. At the same dose and with the same treatment strategies, MEAN was more efficacious in inhibiting tumor growth in mice than sorafenib, the only approved drug for HCC. Treatment by MEAN at an effective dose for 6 wk was well tole...
Source: FASEB Journal - November 30, 2017 Category: Biology Authors: Liu, Y., Lou, G., Norton, J. T., Wang, C., Kandela, I., Tang, S., Shank, N. I., Gupta, P., Huang, M., Avram, M. J., Green, R., Mazar, A., Appella, D., Chen, Z., Huang, S. Tags: Research Source Type: research
Nicotinamide riboside, a form of vitamin B3, protects against excitotoxicity-induced axonal degeneration [Research]
NAD+ depletion is a common phenomenon in neurodegenerative pathologies. Excitotoxicity occurs in multiple neurologic disorders and NAD+ was shown to prevent neuronal degeneration in this process through mechanisms that remained to be determined. The activity of nicotinamide riboside (NR) in neuroprotective models and the recent description of extracellular conversion of NAD+ to NR prompted us to probe the effects of NAD+ and NR in protection against excitotoxicity. Here, we show that intracortical administration of NR but not NAD+ reduces brain damage induced by NMDA injection. Using cortical neurons, we found that provisi...
Source: FASEB Journal - November 30, 2017 Category: Biology Authors: Vaur, P., Brugg, B., Mericskay, M., Li, Z., Schmidt, M. S., Vivien, D., Orset, C., Jacotot, E., Brenner, C., Duplus, E. Tags: Research Source Type: research
Cell-autonomous cytotoxicity of type I interferon response via induction of endoplasmic reticulum stress [Research]
In this study, the classic non–cell-autonomous cytotoxicity of IFN was augmented by cell-autonomous mechanisms that operated independently of the interaction of IFN with its receptors. Cells primed to produce IFN by 5-azacytidine (5-aza) underwent endoplasmic reticulum (ER) stress. The chemical chaperones tauroursodeoxycholate (TUDCA) and 4-phenylbutyrate (4-PBA), as well as the iron chelator ciclopirox (CPX), which reduces ER stress, alleviated the cytotoxicity of 5-aza. Ablation of CCAAT-enhancer-binding protein homologous protein (CHOP), the major ER stress–associated proapoptotic transcription factor, prote...
Source: FASEB Journal - November 30, 2017 Category: Biology Authors: Mihailidou, C., Papavassiliou, A. G., Kiaris, H. Tags: Research Source Type: research
A critical role for plasma kallikrein in the pathogenesis of autoantibody-induced arthritis [Research]
In this study, we generated 2 knockout mouse strains that lacked pKal and HK and determined the role of KKS in autoantibody-induced arthritis. In a K/BxN serum transfer-induced arthritis (STIA) model, mice that lacked HK, pKal, or bradykinin receptors displayed protective phenotypes in joint swelling, histologic changes in inflammation, and cytokine production; however, FXII-deficient mice developed normal arthritis. Inhibition of Kal ameliorated arthritis severity and incidence at early stage STIA and reduced the levels of major cytokines in joints. In addition to releasing bradykinin from HK, Kal directly activated monoc...
Source: FASEB Journal - November 30, 2017 Category: Biology Authors: Yang, A., Zhou, J., Wang, B., Dai, J., Colman, R. W., Song, W., Wu, Y. Tags: Research Source Type: research
Amyloid-{beta} and islet amyloid pathologies link Alzheimers disease and type 2 diabetes in a transgenic model [Research]
Alzheimer’s disease (AD) and type 2 diabetes (T2D) present a significant risk to each other. AD and T2D are characterized by deposition of cerebral amyloid-β (Aβ) and pancreatic human islet amyloid polypeptide (hIAPP), respectively. We investigated the role of amyloidogenic proteins in the interplay between these diseases. A novel double transgenic mouse model combining T2D and AD was generated and characterized. AD-related amyloid transgenic mice coexpressing hIAPP displayed peripheral insulin resistance, hyperglycemia, and glucose intolerance. Aβ and IAPP amyloid co-deposition increased tau phosphory...
Source: FASEB Journal - November 30, 2017 Category: Biology Authors: Wijesekara, N., Ahrens, R., Sabale, M., Wu, L., Ha, K., Verdile, G., Fraser, P. E. Tags: Research Source Type: research
Lipidomic and proteomic analysis of exosomes from mouse cortical collecting duct cells [Research]
Exosomes are endosome-derived nanovesicles that are involved in cellular communication and signaling. Exosomes are produced by epithelial cells and are found in biologic fluids including blood and urine. The packaged material within exosomes includes proteins and lipids, but the molecular comparison within exosome subtypes is largely unknown. The purpose of this study was to investigate differences between exosomes derived from the apical plasma membrane and basolateral plasma membrane of polarized murine cortical collecting duct principal cells. Nanoparticle tracking analysis showed that the size and concentration of apic...
Source: FASEB Journal - November 30, 2017 Category: Biology Authors: Dang, V. D., Jella, K. K., Ragheb, R. R. T., Denslow, N. D., Alli, A. A. Tags: Research Source Type: research
The specialized proresolving lipid mediator maresin 1 protects hepatocytes from lipotoxic and hypoxia-induced endoplasmic reticulum stress [Research]
Endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) are hallmarks of nonalcoholic fatty liver disease (NAFLD), which is the hepatic manifestation of the metabolic syndrome associated with obesity. The specialized proresolving lipid mediator maresin 1 (MaR1) preserves tissue homeostasis by exerting cytoprotective actions, dampening inflammation, and expediting its timely resolution. Here, we explored whether MaR1 protects liver cells from lipotoxic and hypoxia-induced ER stress. Mice were rendered obese by high-fat diet feeding, and experiments were performed in primary hepatocytes, Kupff...
Source: FASEB Journal - November 30, 2017 Category: Biology Authors: Rius, B., Duran-Güell, M., Flores-Costa, R., Lopez-Vicario, C., Lopategi, A., Alcaraz-Quiles, J., Casulleras, M., Lozano, J. J., Titos, E., Claria, J. Tags: Research Source Type: research
Maternal Western diet age-specifically alters female offspring voluntary physical activity and dopamine- and leptin-related gene expression [Research]
Prenatal overnutrition affects development into adulthood and influences risk of obesity. We assessed the transgenerational effect of maternal Western diet (WD) consumption on offspring physical activity. Voluntary wheel running was increased in juvenile (4–7 wk of age), but decreased in adult (16–19 wk of age), F1 female WD offspring. In contrast, no wheel-running differences in F1 male offspring were observed. Increased wheel running in juvenile female WD offspring was associated with up-regulated dopamine receptor (DRD)-1 and -2 in the nucleus accumbens (NAc) and with down-regulated Lepr in the ventral tegme...
Source: FASEB Journal - November 30, 2017 Category: Biology Authors: Ruegsegger, G. N., Grigsby, K. B., Kelty, T. J., Zidon, T. M., Childs, T. E., Vieira-Potter, V. J., Klinkebiel, D. L., Matheny, M., Scarpace, P. J., Booth, F. W. Tags: Research Source Type: research
Antibody-mediated blockade of JMJD6 interaction with collagen I exerts antifibrotic and antimetastatic activities [Research]
JMJD6 is known to localize in the nucleus, exerting histone arginine demethylase and lysyl hydroxylase activities. A novel localization of JMJD6 in the extracellular matrix, resulting from its secretion as a soluble protein, was unveiled by a new anti-JMJD6 mAb called P4E11, which was developed to identify new targets in the stroma. Recombinant JMJD6 binds with collagen type I (Coll-I), and distinct JMJD6 peptides interfere with collagen fibrillogenesis, collagen-fibronectin interaction, and adhesion of human tumor cells to the collagen substrate. P4E11 and collagen binding to JMJD6 are mutually exclusive because the amino...
Source: FASEB Journal - November 30, 2017 Category: Biology Authors: Miotti, S., Gulino, A., Ferri, R., Parenza, M., Chronowska, A., Lecis, D., Sangaletti, S., Tagliabue, E., Tripodo, C., Colombo, M. P. Tags: Research Source Type: research
Glucose potentiates {beta}-cell function by inducing Tph1 expression in rat islets [Research]
Impaired pancreatic β-cell function is the primary defect in type 2 diabetes. Glucose is an important regulator of β-cell growth and function; however, the mechanisms that are involved in the chronic adaptation of β cells to hyperglycemia remain largely unknown. In the present study, global gene expression patterns revealed that tryptophan hydroxylase 1 (Tph1) was the most profound of genes that are up-regulated in rat islets exposed to high glucose. Calcium and cAMP signals synergistically mediated glucose-stimulated Tph1 transcription in β cells by activating cAMP-responsive element–binding prot...
Source: FASEB Journal - November 30, 2017 Category: Biology Authors: Zhang, Y., Deng, R., Yang, X., Xu, W., Liu, Y., Li, F., Zhang, J., Tang, H., Ji, X., Bi, Y., Wang, X., Zhou, L., Ning, G. Tags: Research Source Type: research
Internal epithelia in Drosophila display rudimentary competence to form cytoplasmic networks of transgenic human vimentin [Research]
Cytoplasmic intermediate filaments (cIFs) are found in all eumetazoans, except arthropods. To investigate the compatibility of cIFs in arthropods, we expressed human vimentin (hVim), a cIF with filament-forming capacity in vertebrate cells and tissues, transgenically in Drosophila. Transgenic hVim could be recovered from whole-fly lysates by using a standard procedure for intermediate filament (IF) extraction. When this procedure was used to test for the possible presence of IF-like proteins in flies, only lamins and tropomyosin were observed in IF-enriched extracts, thereby providing biochemical reinforcement to the parad...
Source: FASEB Journal - November 30, 2017 Category: Biology Authors: Gullmets, J., Torvaldson, E., Lindqvist, J., Imanishi, S. Y., Taimen, P., Meinander, A., Eriksson, J. E. Tags: Research Source Type: research
IFN-{gamma} aggravates neointimal hyperplasia by inducing endoplasmic reticulum stress and apoptosis in macrophages by promoting ubiquitin-dependent liver X receptor-{alpha} degradation [Research]
Neointimal hyperplasia is the main cause of restenosis after percutaneous coronary interventions (PCIs). Both IFN- and macrophages play nonredundant roles in the pathogenesis of vascular intimal hyperplasia; however, the underlying mechanisms remain elusive and must be further investigated. In mouse peritoneal macrophages, IFN- significantly accelerated degradation and up-regulated polyubiquitination of liver X receptor (LXR)-α. Signal transducer and activator of transcription 1 (STAT1) inhibitor, fludarabine, and PIAS1 knockdown reduced ubiquitination and increased the expression of LXR-α in IFN-–treated...
Source: FASEB Journal - November 30, 2017 Category: Biology Authors: Zhao, Q., Zhou, D., You, H., Lou, B., Zhang, Y., Tian, Y., Guo, N., Chen, X., Liu, Y., Wu, Y., Yuan, Z., Zhou, J. Tags: Research Source Type: research
