Eliciting improved antibacterial efficacy of host proteins in the presence of antibiotics [Research]
We recently reported the aptitude of a membrane-active lipopeptide (C10OOc12O) to sensitize gram-negative bacilli (GNB) to host antibacterial proteins. Here we explored the potential of harnessing such capacity in the presence of antibiotics. For this purpose, we compared Escherichia coli sensitization to antibiotics in broth and plasma; assessed inner and outer membrane damages using scanning electron microscopy, dyes, and mutant strains; and assessed the ability to affect disease course using the mouse peritonitis–sepsis model for mono- and combination therapies. We found that by altering permeability of both outer...
Source: FASEB Journal - January 2, 2018 Category: Biology Authors: Jammal, J., Zaknoon, F., Mor, A. Tags: Research Source Type: research
Effects of aging and resistance training in rat tendon remodeling [Research]
In elderly persons, weak tendons contribute to functional limitations, injuries, and disability, but resistance training can attenuate this age-related decline. We evaluated the effects of resistance training on the extracellular matrix (ECM) of the calcaneal tendon (CT) in young and old rats and its effect on tendon remodeling. Wistar rats aged 3 mo (young, n = 30) and 20 mo (old, n = 30) were divided into 4 groups: young sedentary, young trained, old sedentary (OS), and old trained (OT). The training sessions were conducted over a 12-wk period. Aging in sedentary rats showed down-regulation in key genes that regulated EC...
Source: FASEB Journal - January 2, 2018 Category: Biology Authors: Marqueti, R. C., Durigan, J. L. Q., Oliveira, A. J. S., Mekaro, M. S., Guzzoni, V., Aro, A. A., Pimentel, E. R., Selistre-de-Araujo, H. S. Tags: Research Source Type: research
BaP exposure causes oocyte meiotic arrest and fertilization failure to weaken female fertility [Research]
Benzo[a]pyrene (BaP) is a ubiquitous environmental pollutant and carcinogen that is frequently found in particulate matter, with a diameter of ≤2.5 μm (PM2.5). It has been reported to interrupt the normal reproductive system, but the exact molecular basis has not been clearly defined. To understand the underlying mechanisms regarding how BaP exposure disrupts female fertility, we evaluated oocyte quality by assessing the critical regulators and events during oocyte meiotic maturation and fertilization. We found that BaP exposure compromised the mouse oocyte meiotic progression by disrupting normal spindle assembly, c...
Source: FASEB Journal - January 2, 2018 Category: Biology Authors: Zhang, M., Miao, Y., Chen, Q., Cai, M., Dong, W., Dai, X., Lu, Y., Zhou, C., Cui, Z., Xiong, B. Tags: Research Source Type: research
GTRAP3-18 regulates food intake and body weight by interacting with pro-opiomelanocortin [Research]
Pro-opiomelanocortin (POMC)-expressing neurons provide α-melanocyte–stimulating hormone (α-MSH), which stimulates melanocortin 4 receptor to induce hypophagia by AMPK inhibition in the hypothalamus. α-MSH is produced by POMC cleavage in secretory granules and released. However, it is not known yet whether any posttranscriptional regulatory mechanism of POMC signaling exists upstream of the secretory granules in neurons. Here we show that glutamate transporter–associated protein 3-18 (GTRAP3-18), an anchor protein that retains interacting proteins in the endoplasmic reticulum, is a critical reg...
Source: FASEB Journal - January 2, 2018 Category: Biology Authors: Aoyama, K., Bhadhprasit, W., Watabe, M., Wang, F., Matsumura, N., Nakaki, T. Tags: Research Source Type: research
PI3K{gamma} ablation does not promote diabetes in db/db mice, but improves insulin sensitivity and reduces pancreatic {beta}-cell apoptosis [Research]
PI3K has emerged as a promising target for the treatment of obesity and insulin resistance; however, previous studies have indicated that PI3K activity in pancreatic β cells is required for normal insulin secretion in response to glucose. Hence, a possible deterioration of insulin secretion capacity in patients who are predisposed to the failure of pancreatic β-cell function is a major concern for the pharmacologic inhibition of PI3K. To address this issue, we investigated the effects of PI3K ablation in db/db diabetic mice, a genetic model of obesity-driven β-cell failure and diabetes. Mice that lacked PI3K...
Source: FASEB Journal - January 2, 2018 Category: Biology Authors: Breasson, L., Sardi, C., Becattini, B., Zani, F., Solinas, G. Tags: Research Source Type: research
{alpha}-Linolenic acid-derived metabolites from gut lactic acid bacteria induce differentiation of anti-inflammatory M2 macrophages through G protein-coupled receptor 40 [Research]
In this study, we examined the effect of ALA and its gut lactic acid bacteria metabolites 13-hydroxy-9(Z),15(Z)-octadecadienoic acid (13-OH) and 13-oxo-9(Z),15(Z)-octadecadienoic acid (13-oxo) on the differentiation of M2 macrophages from bone marrow–derived cells (BMDCs) and investigated the underlying mechanisms. BMDCs were stimulated with ALA, 13-OH, or 13-oxo in the presence of IL-4 or IL-13 for 24 h, and significant increases in M2 macrophage markers CD206 and Arginase-1 (Arg1) were observed. In addition, M2 macrophage phenotypes were less prevalent following cotreatment with GPCR40 antagonists or inhibitors of ...
Source: FASEB Journal - January 2, 2018 Category: Biology Authors: Ohue-Kitano, R., Yasuoka, Y., Goto, T., Kitamura, N., Park, S.-B., Kishino, S., Kimura, I., Kasubuchi, M., Takahashi, H., Li, Y., Yeh, Y.-S., Jheng, H.-F., Iwase, M., Tanaka, M., Masuda, S., Inoue, T., Yamakage, H., Kusakabe, T., Tani, F., Shimatsu, A., T Tags: Research Source Type: research
FFAR2-FFAR3 receptor heteromerization modulates short-chain fatty acid sensing [Research]
Free fatty acid receptors 2 and 3 (FFAR2/FFA2/GPR43 and FFAR3/FFA3/GPR41) are mammalian receptors for gut microbiota–derived short-chain fatty acids (SCFAs). These receptors are promising drug targets for obesity, colitis, colon cancer, asthma, and arthritis. Here, we demonstrate that FFAR2 and FFAR3 interact to form a heteromer in primary human monocytes and macrophages via proximity ligation assay, and during heterologous expression in HEK293 cells via bimolecular fluorescence complementation and fluorescence resonance energy transfer. The FFAR2-FFAR3 heteromer displayed enhanced cytosolic Ca2+ signaling (1.5-fold ...
Source: FASEB Journal - January 2, 2018 Category: Biology Authors: Ang, Z., Xiong, D., Wu, M., Ding, J. L. Tags: Research Source Type: research
Endothelial cells promote triple-negative breast cancer cell metastasis via PAI-1 and CCL5 signaling [Research]
Endothelial cells (ECs) in the tumor microenvironment have been reported to play a more active role in solid tumor growth and metastatic dissemination than simply providing the physical structure to form conduits for blood flow; however, the involvement of ECs in the process of triple-negative breast cancer (TNBC) metastasis has not been addressed. Here, we demonstrate that ECs—when mixed with TNBC cells—could increase TNBC cell metastatic potency. After treatment with TGF-β to induce endothelial–mesenchymal transition (EMT), TNBC cells could produce plasminogen activator inhibitor-1 (PAI-1) and stim...
Source: FASEB Journal - January 2, 2018 Category: Biology Authors: Zhang, W., Xu, J., Fang, H., Tang, L., Chen, W., Sun, Q., Zhang, Q., Yang, F., Sun, Z., Cao, L., Wang, Y., Guan, X. Tags: Research Source Type: research
Pronounced energy restriction with elevated protein intake results in no change in proteolysis and reductions in skeletal muscle protein synthesis that are mitigated by resistance exercise [Research]
Preservation of lean body mass (LBM) may be important during dietary energy restriction (ER) and requires equal rates of muscle protein synthesis (MPS) and muscle protein breakdown (MPB). Currently, the relative contribution of MPS and MPB to the loss of LBM during ER in humans is unknown. We aimed to determine the impact of dietary protein intake and resistance exercise on MPS and MPB during a controlled short-term energy deficit. Adult men (body mass index, 28.6 ± 0.6 kg/m2; age 22 ± 1 yr) underwent 10 d of 40%-reduced energy intake while performing unilateral resistance exercise and consuming lower protein...
Source: FASEB Journal - January 2, 2018 Category: Biology Authors: Hector, A. J., McGlory, C., Damas, F., Mazara, N., Baker, S. K., Phillips, S. M. Tags: Research Source Type: research
Myeloid receptor CD36 is required for early phagocytosis of myocardial infarcts and induction of Nr4a1-dependent mechanisms of cardiac repair [Research]
Phagocytosis after myocardial infarction (MI) is a prerequisite to cardiac repair. Recruited monocytes clear necrotic cardiomyocytes and differentiate into cardiac macrophages. Some studies have linked apoptotic cell receptors on cardiac macrophages to tissue repair; however, the contribution of precursor monocyte phagocytic receptors, which are the first to interact with the cardiac parenchyma, is unclear. The scavenger receptor cluster of differentiation (CD)36 protein was detected on cardiac Ly6cHI monocytes, and bone marrow–derived Cd36 was essential for both early phagocytosis of dying cardiomyocytes and for sma...
Source: FASEB Journal - January 2, 2018 Category: Biology Authors: Dehn, S., Thorp, E. B. Tags: Research Source Type: research
Presenilin1/{gamma}-secretase protects neurons from glucose deprivation-induced death by regulating miR-212 and PEA15 [Research]
Reduced cerebral glucose utilization is found in aged individuals and often is an early sign of neurodegeneration. Here, we show that under glucose deprivation (GD) conditions, decreased expression of presenilin 1 (PS1) results in decreased neuronal survival, whereas increased PS1 increases neuronal survival. Inhibition of -secretase also decreases neuronal survival under GD conditions, which suggests the PS1/-secretase system protects neurons from GD-induced death. We also show that neuronal levels of the survival protein, phosphoprotein enriched in astrocytes at ~15 kDa (PEA15), and its mRNA are regulated by PS1/-secreta...
Source: FASEB Journal - January 2, 2018 Category: Biology Authors: Huang, Q., Voloudakis, G., Ren, Y., Yoon, Y., Zhang, E., Kajiwara, Y., Shao, Z., Xuan, Z., Lebedev, D., Georgakopoulos, A., Robakis, N. K. Tags: Research Source Type: research
The deubiquitinating enzyme USP48 stabilizes TRAF2 and reduces E-cadherin-mediated adherens junctions [Research]
The tumor necrosis factor receptor–associated factor 2 (TRAF2) is a second messenger adaptor protein that plays an essential role in propagating TNF-α-mediated signaling pathways. Modulation of TRAF2 activity by ubiquitination is well studied; however, the deubiquitinating enzyme (DUB), which regulates TRAF2 stability, has not been identified. Here we reveal USP48 as the first identified DUB to deubiquitinate and stabilize TRAF2 in epithelial cells. Down-regulation of USP48 increases K48-linked polyubiquitination of TRAF2 and reduces TRAF2 protein levels. Interestingly, USP48 only targets the TRAF2 related to J...
Source: FASEB Journal - January 2, 2018 Category: Biology Authors: Li, S., Wang, D., Zhao, J., Weathington, N. M., Shang, D., Zhao, Y. Tags: Research Source Type: research
Organ- and cell-specific immune responses are associated with the outcomes of intracerebral hemorrhage [Research]
Severe brain injury significantly influences immune responses; however, the levels at which this influence occurs and which neurogenic pathways are involved are not well defined. Here, we used MRI to measure spleen volume and tissue diffusion changes in patients with intracerebral hemorrhage (ICH). We observed increased capillary exchange and spleen shrinkage by d 3 post-ICH, with recovery by d 14. The extent of spleen shrinkage was associated with brain hematoma size, and a reduced progression of perihematomal edema was observed in the presence of severe spleen shrinkage. At the cellular level, lymphopenia was present in ...
Source: FASEB Journal - January 2, 2018 Category: Biology Authors: Zhang, J., Shi, K., Li, Z., Li, M., Han, Y., Wang, L., Zhang, Z., Yu, C., Zhang, F., Song, L., Dong, J.-F., La Cava, A., Sheth, K. N., Shi, F.-D. Tags: Research Source Type: research
Proline-dependent and basophilic kinases phosphorylate human TRPC6 at serine 14 to control channel activity through increased membrane expression [Research]
In this study, an unbiased phosphoproteomic screen of human TRPC6 identified several novel serine phosphorylation sites. The phosphorylation site at serine 14 of TRPC6 is embedded in a basophilic kinase motif that is highly conserved across species. We confirmed serine 14 as a target of MAPKs and proline-directed kinases like cyclin-dependent kinase 5 (Cdk5) in cell-based as well as in vitro kinase assays and quantitative phosphoproteomic analysis of TRPC6. Phosphorylation of TRPC6 at serine 14 enhances channel conductance by boosting membrane expression of TRPC6, whereas protein stability and multimerization of TRPC6 are ...
Source: FASEB Journal - January 2, 2018 Category: Biology Authors: Hagmann, H., Mangold, N., Rinschen, M. M., Koenig, T., Kunzelmann, K., Schermer, B., Benzing, T., Brinkkoetter, P. T. Tags: Research Source Type: research
Dyslipidemia impairs mitochondrial trafficking and function in sensory neurons [Research]
Mitochondrial trafficking plays a central role in dorsal root ganglion (DRG) neuronal cell survival and neurotransmission by transporting mitochondria from the neuronal cell body throughout the bundles of DRG axons. In type 2 diabetes (T2DM), dyslipidemia and hyperglycemia damage DRG neurons and induce mitochondrial dysfunction; however, the impact of free fatty acids and glucose on mitochondrial trafficking in DRG neurons remains unknown. To evaluate the impact of free fatty acids compared to hyperglycemia on mitochondrial transport, primary adult mouse DRG neuron cultures were treated with physiologic concentrations of p...
Source: FASEB Journal - January 2, 2018 Category: Biology Authors: Rumora, A. E., Lentz, S. I., Hinder, L. M., Jackson, S. W., Valesano, A., Levinson, G. E., Feldman, E. L. Tags: Research Source Type: research
