Womens Health Now, Yet So Far to Go [Editorial]
(Source: FASEB Journal)
Source: FASEB Journal - November 30, 2017 Category: Biology Tags: Editorial Source Type: research
Erratum [Erratum]
(Source: FASEB Journal)
Source: FASEB Journal - November 1, 2017 Category: Biology Tags: Erratum Source Type: research
The glucocorticoid receptor in monocyte-derived macrophages is critical for cardiac infarct repair and remodeling [Research]
Cell- and tissue-specific actions of glucocorticoids are mediated by the glucocorticoid receptor. Here, we demonstrate that the glucocorticoid receptor (GR) in macrophages is essential for cardiac healing after myocardial infarction. Compared with GRflox (wild-type controls), GRLysMCre mice that lacked GR in myeloid cells showed increased acute mortality as a result of cardiac rupture. Seven days after left coronary artery ligation, GRLysMCre mice exhibited worse cardiac function and adverse remodeling associated with impaired scar formation and angiogenic response to ischemic injury. Inactivation of GR altered the functio...
Source: FASEB Journal - November 1, 2017 Category: Biology Authors: Galuppo, P., Vettorazzi, S., Hövelmann, J., Scholz, C.-J., Tuckermann, J. P., Bauersachs, J., Fraccarollo, D. Tags: Research Source Type: research
Engineered islet cell clusters transplanted into subcutaneous space are superior to pancreatic islets in diabetes [Research]
An alternative route for pancreatic islet transplantation is the subcutaneous space; however, inadequate vascularization in the subcutaneous space limits the availability of oxygen and nutrients to the subcutaneously transplanted islets, which leads to the development of a necrotic core in the islets, thereby causing islet dysfunction. Thus, we aimed to prevent the early apoptosis of pancreatic islets after transplantation into subcutaneous space by preparing islet clusters of appropriate size. We prepared fully functional islet cell clusters (ICCs) by using the hanging-drop technique. We optimized the size of ICCs on the ...
Source: FASEB Journal - November 1, 2017 Category: Biology Authors: Pathak, S., Regmi, S., Gupta, B., Pham, T. T., Yong, C. S., Kim, J. O., Yook, S., Kim, J.-R., Park, M. H., Bae, Y. K., Jeong, J.-H. Tags: Research Source Type: research
Macrophage migration inhibitory factor enhances Pseudomonas aeruginosa biofilm formation, potentially contributing to cystic fibrosis pathogenesis [Research]
We describe for the first time how Pseudomonas aeruginosa can utilize human recombinant MIF (rMIF) to significantly (P < 0.01) enhance its endogenous biofilm formation. Our in vivo studies demonstrate that utilizing a small-molecular-weight inhibitor targeting MIF’s tautomerase activity (SCD-19) significantly reduces the inflammatory response in a murine pulmonary chronic P. aeruginosa model. In addition, we show that in in vitro experiments, pretreatment of P. aeruginosa with rMIF is associated with reduced bacterial killing by tobramycin. Our novel findings support the concept of an anti-MIF strategy that target...
Source: FASEB Journal - November 1, 2017 Category: Biology Authors: Tynan, A., Mawhinney, L., Armstrong, M. E., OReilly, C., Kennedy, S., Caraher, E., Jülicher, K., ODwyer, D., Maher, L., Schaffer, K., Fabre, A., McKone, E. F., Leng, L., Bucala, R., Bernhagen, J., Cooke, G., Donnelly, S. C. Tags: Research Source Type: research
Leishmania donovani inhibits inflammasome-dependent macrophage activation by exploiting the negative regulatory proteins A20 and UCP2 [Research]
In visceral leishmaniasis, we found that the antileishmanial drug Amp B produces a higher level of IL-1β over the infected control. Moreover, administering anti-IL-1β antibody to infected Amp B–treated mice showed significantly less parasite clearance. Investigation revealed that Leishmania inhibits stimuli-induced expression of a multiprotein signaling platform, NLRP3 inflammasome, which in turn inhibits caspase-1 activation mediated maturation of IL-1β from its pro form. Attenuation of NLRP3 and pro-IL-1β in infection was found to result from decreased NF-B activity. Transfecting infected cells ...
Source: FASEB Journal - November 1, 2017 Category: Biology Authors: Gupta, A. K., Ghosh, K., Palit, S., Barua, J., Das, P. K., Ukil, A. Tags: Research Source Type: research
E-selectin-mediated rolling facilitates pancreatic cancer cell adhesion to hyaluronic acid [Research]
Tumor cell extravasation is a multistep process preceded by cell rolling and arrest on the vessel wall via the formation of specific receptor–ligand bonds. The strength, availability, and number of receptor–ligand bonds regulate the rate by which tumor cells tether, roll, and adhere to vascular walls. Although the mechanics of selectin-mediated rolling have been extensively studied, little is known regarding how tumor cell rolling on selectins facilitates adhesion to a distinct substrate-bound protein with different kinetic properties. By using multicomponent protein patterning and a microfluidic system, we eva...
Source: FASEB Journal - November 1, 2017 Category: Biology Authors: Shea, D. J., Li, Y. W., Stebe, K. J., Konstantopoulos, K. Tags: Research Source Type: research
Hypoxia reduces mature hERG channels through calpain up-regulation [Research]
Human ether-a-go-go-related gene (hERG) encodes the pore-forming subunit of the rapidly activating delayed rectifier potassium current (IKr) potassium channel, which is important for cardiac repolarization. Impairment of hERG function is the primary cause of acquired long QT syndrome, which predisposes individuals to cardiac arrhythmias and sudden death. Patients with hypoxia due to conditions such as cardiac ischemia or obstructive sleep apnea display increased incidence of cardiac arrhythmias and sudden death. We sought to understand the mechanisms that underlie hypoxia-associated cardiac arrhythmias. Using cell biology ...
Source: FASEB Journal - November 1, 2017 Category: Biology Authors: Lamothe, S. M., Song, W., Guo, J., Li, W., Yang, T., Baranchuk, A., Graham, C. H., Zhang, S. Tags: Research Source Type: research
Astrocytes from the brain microenvironment alter migration and morphology of metastatic breast cancer cells [Research]
Tumor cell metastasis to the brain involves cell migration through biochemically and physically complex microenvironments at the blood–brain barrier (BBB). The current understanding of tumor cell migration across the BBB is limited. We hypothesize that an interplay between biochemical cues and physical cues at the BBB affects the mechanisms of brain metastasis. We found that astrocyte conditioned medium (ACM) applied directly to tumor cells increased tumor cell velocity, induced elongation, and promoted actin stress fiber organization. Notably, treatment of the extracellular matrix with ACM led to even more significa...
Source: FASEB Journal - November 1, 2017 Category: Biology Authors: Shumakovich, M. A., Mencio, C. P., Siglin, J. S., Moriarty, R. A., Geller, H. M., Stroka, K. M. Tags: Research Source Type: research
10-oxo-12(Z)-octadecenoic acid, a linoleic acid metabolite produced by gut lactic acid bacteria, enhances energy metabolism by activation of TRPV1 [Research]
Gut microbiota can regulate the host energy metabolism; however, the underlying mechanisms that could involve gut microbiota–derived compounds remain to be understood. Therefore, in this study, we investigated the effects of KetoA [10-oxo-12(Z)-octadecenoic acid]—a linoleic acid metabolite produced by gut lactic acid bacteria—on whole-body energy metabolism and found that dietary intake of KetoA could enhance energy expenditure in mice, thereby protecting mice from diet-induced obesity. By using Ca2+ imaging and whole-cell patch-clamp methods, KetoA was noted to potently activate transient receptor potent...
Source: FASEB Journal - November 1, 2017 Category: Biology Authors: Kim, M., Furuzono, T., Yamakuni, K., Li, Y., Kim, Y.-I., Takahashi, H., Ohue-Kitano, R., Jheng, H.-F., Takahashi, N., Kano, Y., Yu, R., Kishino, S., Ogawa, J., Uchida, K., Yamazaki, J., Tominaga, M., Kawada, T., Goto, T. Tags: Research Source Type: research
Angiotensin II regulates phosphorylation of actin-associated proteins in human podocytes [Research]
In this study, we used stable isotope labeling with amino acids in cell culture coupled to mass spectrometry to characterize relative changes in the phosphoproteome of human podocytes in response to short-term treatment with AngII. In 4 replicates, we identified a total of 17,956 peptides that were traceable to 2081 distinct proteins. Bioinformatic analyses revealed that among the increasingly phosphorylated peptides are predominantly peptides that are related to actin filaments, cytoskeleton, lamellipodia, mammalian target of rapamycin, and MAPK signaling. Among others, this screening approach highlighted the increased ph...
Source: FASEB Journal - November 1, 2017 Category: Biology Authors: Schenk, L. K., Möller-Kerutt, A., Klosowski, R., Wolters, D., Schaffner-Reckinger, E., Weide, T., Pavenstädt, H., Vollenbröker, B. Tags: Research Source Type: research
UBAP2L is amplified in a large subset of human lung adenocarcinoma and is critical for epithelial lung cell identity and tumor metastasis [Research]
The ubiquitin-associated protein 2–like (UBAP2L) gene remains poorly studied in human and mouse development. UBAP2L interacts with the Polycomb group protein B lymphoma Mo-MLV insertion region 1 homolog (BMI1) and determines the activity of mouse hematopoietic stem cells in vivo. Here we show that loss of Ubap2l leads to disorganized respiratory epithelium of mutant neonates, which die of respiratory failure. We also show that UBAP2L overexpression leads to epithelial-mesenchymal transition–like phenotype in a non-small cell lung carcinoma (NSCLC) cell line. UBAP2L is amplified in 15% of human primary lung aden...
Source: FASEB Journal - November 1, 2017 Category: Biology Authors: Aucagne, R., Girard, S., Mayotte, N., Lehnertz, B., Lopes-Paciencia, S., Gendron, P., Boucher, G., Chagraoui, J., Sauvageau, G. Tags: Research Source Type: research
EGCG ameliorates high-fat- and high-fructose-induced cognitive defects by regulating the IRS/AKT and ERK/CREB/BDNF signaling pathways in the CNS [Research]
In this study, our goal was to investigate the protective effects of EGCG treatment on insulin resistance and memory impairment induced by a high-fat and high-fructose diet (HFFD). We randomly assigned 3-mo-old C57BL/6J mice to 3 groups with different diets: control group, HFFD group, and HFFD plus EGCG group. Memory loss was assessed by using the Morris water maze test, during which EGCG was observed to prevent HFFD-elicited memory impairment and neuronal loss. Consistent with these results, EGCG attenuated HFFD-induced neuronal damage. Of note, EGCG significantly ameliorated insulin resistance and cognitive disorder by u...
Source: FASEB Journal - November 1, 2017 Category: Biology Authors: Mi, Y., Qi, G., Fan, R., Qiao, Q., Sun, Y., Gao, Y., Liu, X. Tags: Research Source Type: research
A2A adenosine receptors control pancreatic dysfunction in high-fat-diet-induced obesity [Research]
Adenosine, a key extracellular signaling mediator, regulates several aspects of metabolism by activating 4 G-protein-coupled receptors, the A1, A2A, A2B, and A3 adenosine receptors (ARs). The role of A2AARs in regulating high-fat-diet (HFD)–induced metabolic derangements is unknown. To evaluate the role of A2AARs in regulating glucose and insulin homeostasis in obesity, we fed A2AAR-knockout (KO) and control mice an HFD for 16 wk to initiate HFD-induced metabolic disorder. We found that genetic deletion of A2AARs caused impaired glucose tolerance in mice fed an HFD. This impaired glucose tolerance was caused by a dec...
Source: FASEB Journal - November 1, 2017 Category: Biology Authors: Csoka, B., Töro, G., Vindeirinho, J., Varga, Z. V., Koscso, B., Nemeth, Z. H., Kokai, E., Antonioli, L., Suleiman, M., Marchetti, P., Cseri, K., Deak, A., Virag, L., Pacher, P., Bai, P., Hasko, G. Tags: Research Source Type: research
Hypoxia-inducible protein 2 Hig2/Hilpda mediates neutral lipid accumulation in macrophages and contributes to atherosclerosis in apolipoprotein E-deficient mice [Research]
Recently we identified hypoxia-inducible protein 2 (HIG2)/hypoxia-inducible lipid droplet–associated (HILPDA) as lipid droplet (LD) protein. Because HILPDA is highly expressed in atherosclerotic plaques, we examined its regulation and function in murine macrophages, compared it to the LD adipose differentiation-related protein (Adrp)/perilipin 2 (Plin2), and investigated its effects on atherogenesis in apolipoprotein E–deficient (ApoE–/–) mice. Tie2-Cre-driven Hilpda conditional knockout (cKO) did not affect viability, proliferation, and ATP levels in macrophages. Hilpda proved to be a target of hyp...
Source: FASEB Journal - November 1, 2017 Category: Biology Authors: Maier, A., Wu, H., Cordasic, N., Oefner, P., Dietel, B., Thiele, C., Weidemann, A., Eckardt, K.-U., Warnecke, C. Tags: Research Source Type: research
