The amyloid precursor protein modulates {alpha}2A-adrenergic receptor endocytosis and signaling through disrupting arrestin 3 recruitment [Research]
In this study, we identified a novel direct interaction between APP and the α2A-adrenergic receptor (α2AAR) that occurs at the intracellular domains of both proteins. The APP interaction with α2AAR is promoted by agonist stimulation and competes with arrestin 3 binding to the receptor. Consequently, the presence of APP attenuates α2AAR internalization and desensitization, which are arrestin-dependent processes. Furthermore, in neuroblastoma neuro-2A cells and primary superior cervical ganglion neurons, where APP is highly expressed, the lack of APP leads to a dramatic increase in plasma membrane rec...
Source: FASEB Journal - September 28, 2017 Category: Biology Authors: Zhang, F., Gannon, M., Chen, Y., Zhou, L., Jiao, K., Wang, Q. Tags: Research Source Type: research
Declining histone acetyltransferase GCN5 represses BMSC-mediated angiogenesis during osteoporosis [Research]
Angiogenesis is disrupted in age-related and postmenopausal osteoporosis. However, the mechanisms of the disorder remain elusive. We confirmed in this study that, in accordance with the decrease of H-type vessels, the proangiogenic potential of bone marrow-derived mesenchymal stem cells (BMSCs) declined during osteoporosis. Screening of the histone acetyltransferase family revealed that GCN5 decreased in BMSCs derived from osteoporotic femur. Further analysis identified that GCN5 plays important roles in regulating the proangiogenic potential of BMSCs. GCN5 promoted BMSC-mediated angiogenesis by enhancing H3K9ac levels on ...
Source: FASEB Journal - September 28, 2017 Category: Biology Authors: Jing, H., Liao, L., Su, X., Shuai, Y., Zhang, X., Deng, Z., Jin, Y. Tags: Research Source Type: research
Selective activation of epidermal growth factor receptor in renal proximal tubule induces tubulointerstitial fibrosis [Research]
This study provides definitive evidence that sustained activation of EGFR in proximal epithelia is sufficient to cause spontaneous, progressive renal tubulointerstitial fibrosis, evident by epithelial dedifferentiation, increased myofibroblasts, immune cell infiltration, and increased matrix deposition.—Overstreet, J. M., Wang, Y., Wang, X., Niu, A., Gewin, L. S., Yao, B., Harris, R. C., Zhang, M.-Z. Selective activation of epidermal growth factor receptor in renal proximal tubule induces tubulointerstitial fibrosis. (Source: FASEB Journal)
Source: FASEB Journal - September 28, 2017 Category: Biology Authors: Overstreet, J. M., Wang, Y., Wang, X., Niu, A., Gewin, L. S., Yao, B., Harris, R. C., Zhang, M.-Z. Tags: Research Source Type: research
Protein kinase C{beta} activates fat mass and obesity-associated protein by influencing its ubiquitin/proteasome degradation [Research]
We report that PKCβ positively regulates FTO on the posttranslation level, evidenced by the facts that PKCβ activation contributes to high-glucose-induced FTO up-regulation, and overexpression of PKCβ suppresses ubiquitin-proteasome degradation of FTO, whereas PKCβ inactivation acts in the opposite manner. It was also found that PKCβ can phosphorylate FTO on threonine, and this phosphorylation requires both catalytic and regulatory domains of PKCβ. Moreover, PKCβ inhibition can suppress 3T3-L1 cell differentiation in normal and FTO-overexpressing cells but not in FTO-silenced or -inhibite...
Source: FASEB Journal - September 28, 2017 Category: Biology Authors: Tai, H., Wang, X., Zhou, J., Han, X., Fang, T., Gong, H., Huang, N., Chen, H., Qin, J., Yang, M., Wei, X., Yang, L., Xiao, H. Tags: Research Source Type: research
Calcium/calmodulin-dependent protein kinase regulates the PINK1/Parkin and DJ-1 pathways of mitophagy during sepsis [Research]
During sepsis and shock states, mitochondrial dysfunction occurs. Consequently, adaptive mechanisms, such as fission, fusion, and mitophagy, are induced to eliminate damaged portions or entire dysfunctional mitochondria. The regulatory PINK1/Parkin and DJ-1 pathways are strongly induced by mitochondrial depolarization, although a direct link between loss of mitochondrial membrane potential () and mitophagy has not been identified. Mitochondria also buffer Ca2+, and their buffering capacity is dependent on . Here, we characterize a role for calcium/calmodulin-dependent protein kinase (CaMK) I in the regulation of these mech...
Source: FASEB Journal - September 28, 2017 Category: Biology Authors: Zhang, X., Yuan, D., Sun, Q., Xu, L., Lee, E., Lewis, A. J., Zuckerbraun, B. S., Rosengart, M. R. Tags: Research Source Type: research
GM-CSF- and M-CSF-primed macrophages present similar resolving but distinct inflammatory lipid mediator signatures [Research]
M1 and M2 activated macrophages (Ms) have different roles in inflammation. Because pathogens may first encounter resting cells, we investigated lipid mediator profiles prior to full activation. Human monocytes were differentiated with granulocyte M colony-stimulating factor (GM-CSF) or M colony-stimulating factor (M-CSF), which are known to prime toward M1 or M2 phenotypes, respectively. Lipid mediators released during resting conditions and produced in response to bacterial stimuli (LPS/N-formylmethionyl-leucyl-phenylalanine or peptidoglycan) were quantified by liquid chromatography-mass spectrometry. In resting condition...
Source: FASEB Journal - September 28, 2017 Category: Biology Authors: Lukic, A., Larssen, P., Fauland, A., Samuelsson, B., Wheelock, C. E., Gabrielsson, S., Radmark, O. Tags: Research Source Type: research
Omega-3 fatty acids increase the unfolded protein response and improve amyloid-{beta} phagocytosis by macrophages of patients with mild cognitive impairment [Research]
Macrophages (Ms) of patients with Alzheimer’s disease and mild cognitive impairment (MCI) are defective in amyloid-β1-42 (Aβ) phagocytosis and have low resistance to apoptosis by Aβ. Omega-3 fatty acids (-3s) in vitro and in vivo and the -3 mediator, resolvin D1, in vitro increase Aβ phagocytosis by Ms of patients with MCI. We have investigated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress by Ms in a longitudinal study of fish-derived, -3–supplemented patients with MCI. Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein...
Source: FASEB Journal - September 28, 2017 Category: Biology Authors: Olivera-Perez, H. M., Lam, L., Dang, J., Jiang, W., Rodriguez, F., Rigali, E., Weitzman, S., Porter, V., Rubbi, L., Morselli, M., Pellegrini, M., Fiala, M. Tags: Research Source Type: research
Notch1 deficiency in postnatal neural progenitor cells in the dentate gyrus leads to emotional and cognitive impairment [Research]
It is well known that Notch1 signaling plays a crucial role in embryonic neural development and adult neurogenesis. The latest evidence shows that Notch1 also plays a critical role in synaptic plasticity in mature hippocampal neurons. So far, deeper insights into the function of Notch1 signaling during the different steps of adult neurogenesis are still lacking, and the mechanisms by which Notch1 dysfunction is associated with brain disorders are also poorly understood. In the current study, we found that Notch1 was highly expressed in the adult-born immature neurons in the hippocampal dentate gyrus. Using a genetic approa...
Source: FASEB Journal - September 28, 2017 Category: Biology Authors: Feng, S., Shi, T., Qiu, J., Yang, H., Wu, Y., Zhou, W., Wang, W., Wu, H. Tags: Research Source Type: research
Targeting acetylcholine receptor M3 prevents the progression of airway hyperreactivity in a mouse model of childhood asthma [Research]
In this study, we identified an age-related mechanism along the cholinergic nerve–airway smooth muscle (ASM) axis that underlies prolonged airway hyperreactivity (AHR) in mice. We showed that ASM continued to mature until ~3 wk after birth. Coinciding with postnatal ASM maturation, there was a critical time window for the development of ASM hypercontractility after cholinergic stimulation. We found that allergen exposure in neonatal mice, but not in adult mice, elevated the level and activity of cholinergic nerves (termed neuroplasticity). We demonstrated that cholinergic neuroplasticity is necessary for the inductio...
Source: FASEB Journal - September 28, 2017 Category: Biology Authors: Patel, K. R., Bai, Y., Trieu, K. G., Barrios, J., Ai, X. Tags: Research Source Type: research
Prenatal nicotinic exposure prolongs superior laryngeal C-fiber-mediated apnea and bradycardia through enhancing neuronal TRPV1 expression and excitation [Research]
Maternal cigarette smoke, including prenatal nicotinic exposure (PNE), is responsible for sudden infant death syndrome (SIDS). The fatal events of SIDS are characterized by severe bradycardia and life-threatening apneas. Although activation of transient receptor potential vanilloid 1 (TRPV1) of superior laryngeal C fibers (SLCFs) could induce bradycardia and apnea and has been implicated in SIDS pathogenesis, how PNE affects the SLCF-mediated cardiorespiratory responses remains unexplored. Here, we tested the hypothesis that PNE would aggravate the SLCF-mediated apnea and bradycardia via up-regulating TRPV1 expression and ...
Source: FASEB Journal - September 28, 2017 Category: Biology Authors: Gao, X., Zhao, L., Zhuang, J., Zang, N., Xu, F. Tags: Research Source Type: research
Prolonged darkness reduces liver fibrosis in a mouse model of primary sclerosing cholangitis by miR-200b down-regulation [Research]
Melatonin therapy or prolonged exposure to complete darkness reduces biliary hyperplasia and liver fibrosis in bile-duct–ligated (BDL) rats; however, no information exists in primary sclerosing cholangitis (PSC). Thus, we aimed to determine the therapeutic effects of prolonged dark therapy or melatonin administration on hepatic fibrosis in the multidrug resistance gene 2–knockout (Mdr2–/–) mouse model of PSC. Melatonin levels, biliary mass, liver fibrosis, angiogenesis and miR-200b expression were evaluated in wild-type and Mdr2–/– mice exposed to darkness or melatonin treatment or in ma...
Source: FASEB Journal - September 28, 2017 Category: Biology Authors: Wu, N., Meng, F., Zhou, T., Han, Y., Kennedy, L., Venter, J., Francis, H., DeMorrow, S., Onori, P., Invernizzi, P., Bernuzzi, F., Mancinelli, R., Gaudio, E., Franchitto, A., Glaser, S., Alpini, G. Tags: Research Source Type: research
Excess centrosomes induce p53-dependent senescence without DNA damage in endothelial cells [Research]
Tumor blood vessels support tumor growth and progression. Centrosomes are microtubule organization centers in cells, and often up to 30% of tumor endothelial cells (ECs) acquire excess (>2) centrosomes. Although excess centrosomes can lead to aneuploidy and chromosome instability in tumor cells, how untransformed ECs respond to excess centrosomes is poorly understood. We found that the frequency of primary human ECs with excess centrosomes was quickly reduced in a p53-dependent manner. Excess centrosomes in ECs were associated with p53 phosphorylation at Ser33, increased p21 levels, and decreased cell proliferation and ...
Source: FASEB Journal - September 28, 2017 Category: Biology Authors: Yu, Z., Ruter, D. L., Kushner, E. J., Bautch, V. L. Tags: Research Source Type: research
Cathepsin B as a potential cystatin M/E target in the mouse hair follicle [Research]
We report the rescue of the lethal skin phenotype of ichq (Cst6-deficient; Cst6–/–) mice by transgenic, epidermis-specific, reexpression of Cst6 under control of the human involucrin (INV) promoter. Rescued Tg(INV-Cst6)Cst6ichq/ichq mice survive the neonatal phase, but display severe eye pathology and alopecia after 4 mo. We observed keratitis and squamous metaplasia of the corneal epithelium, comparable to Cst6–/–Ctsl+/– mice, as we have reported in other studies. We found the INV promoter to be active in the hair follicle infundibulum; however, we did not observe Cst6 protein expression in t...
Source: FASEB Journal - September 28, 2017 Category: Biology Authors: Oortveld, M. A. W., van Vlijmen-Willems, I. M. J. J., Kersten, F. F. J., Cheng, T., Verdoes, M., van Erp, P. E. J., Verbeek, S., Reinheckel, T., Hendriks, W. J. A. J., Schalkwijk, J., Zeeuwen, P. L. J. M. Tags: Research Source Type: research
Intersectin 2 controls actin cap formation and meiotic division in mouse oocytes through the Cdc42 pathway [Research]
Intersectins (ITSNs), an evolutionarily conserved adaptor protein family, have been implicated in multiple biologic processes; however, their functions in mammalian oocytes have not been addressed. Here, we report delayed meiotic resumption and defective cytokinesis upon specific depletion of ITSN2 in mouse oocytes. In particular, abnormal spindle, misaligned chromosomes, and loss of cortical actin cap are readily observed in ITSN2-depleted oocytes. Similarly, a small molecule that targets the Cdc42–ITSN interaction also disrupts oocyte maturation and actin polymerization. Moreover, we find that ITSN2 depletion reduc...
Source: FASEB Journal - September 28, 2017 Category: Biology Authors: Zhang, J., Ma, R., Li, L., Wang, L., Hou, X., Han, L., Ge, J., Li, M., Wang, Q. Tags: Research Source Type: research
Epidermal growth factor-induced pyruvate dehydrogenase kinase 1 expression enhances head and neck squamous cell carcinoma metastasis via up-regulation of fibronectin [Research]
Epidermal growth factor receptor (EGFR) activation is a major cause of metastasis in such cancers as head and neck squamous cell carcinoma (HNSCC); however, whether the metabolic enzyme, pyruvate dehydrogenase kinase 1 (PDK1), mediates EGF-enhanced HNSCC metastasis remains unclear. Of interest, we found that EGF induced PDK1 expression in HNSCC. Tumor cell transformation induced by EGF was repressed by PDK1 knockdown, and the down-regulation of PDK1 expression or inhibition of its activity significantly blocked EGF-enhanced cell migration and invasion. In addition, depletion of PDK1 impeded EGF-enhanced binding of HNSCC ce...
Source: FASEB Journal - September 28, 2017 Category: Biology Authors: Hsu, J.-Y., Chang, J.-Y., Chang, K.-Y., Chang, W.-C., Chen, B.-K. Tags: Research Source Type: research
