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FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology

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https://www.readbyqxmd.com/read/28522596/lysyl-oxidase-overexpression-accelerates-cardiac-remodeling-and-aggravates-angiotensin-ii-induced-hypertrophy
#1
María Galán, Saray Varona, Anna Guadall, Mar Orriols, Miquel Navas, Silvia Aguiló, Alicia de Diego, María A Navarro, David García-Dorado, Antonio Rodríguez-Sinovas, José Martínez-González, Cristina Rodriguez
Lysyl oxidase (LOX) controls matrix remodeling, a key process that underlies cardiovascular diseases and heart failure; however, a lack of suitable animal models has limited our knowledge with regard to the contribution of LOX to cardiac dysfunction. Here, we assessed the impact of LOX overexpression on ventricular function and cardiac hypertrophy in a transgenic mouse model with a strong cardiac expression of human LOX (TgLOX). TgLOX mice exhibited high expression of the transgene in cardiomyocytes and cardiofibroblasts, which are associated with enhanced LOX activity and H2O2 production and with cardiofibroblast reprogramming...
May 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28522595/human-salivary-peptide-histatin-1-stimulates-epithelial-and-endothelial-cell-adhesion-and-barrier-function
#2
Irene A van Dijk, Maria Laura Ferrando, Anne-Eva van der Wijk, Ron A Hoebe, Kamran Nazmi, Wouter J de Jonge, Przemek M Krawczyk, Jan G M Bolscher, Enno C I Veerman, Jan Stap
Histatins are multifunctional histidine-rich peptides secreted by the salivary glands and exclusively present in the saliva of higher primates, where they play a fundamental role in the protection of the oral cavity. Our previously published results demonstrated that histatin-1 (Hst1) promotes cell-substrate adhesion in various cell types and hinted that it could also be involved in cell-cell adhesion, a process of fundamental importance to epithelial and endothelial barriers. Here we explore the effects of Hst1 on cellular barrier function...
May 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28522594/sphingomyelin-synthase-2-deficiency-inhibits-the-induction-of-murine-colitis-associated-colon-cancer
#3
Toshio Ohnishi, Chieko Hashizume, Makoto Taniguchi, Hidehiro Furumoto, Jia Han, Rongfen Gao, Shinichi Kinami, Takeo Kosaka, Toshiro Okazaki
Sphingomyelin synthase 2 (SMS2) is the synthetic enzyme of sphingomyelin (SM), which regulates membrane fluidity and microdomain structure. SMS2 plays a role in LPS-induced lung injury and inflammation; however, its role in inflammation-mediated tumorigenesis is unclear. We investigated the effect of SMS2 deficiency on dextran sodium sulfate (DSS)-induced murine colitis and found inhibition of DSS-induced inflammation in SMS2-deficient (SMS2(-/-)) mice. DSS treatment induced a significant increase in ceramide levels, with a decrease of SM levels in SMS2(-/-) colon tissue, and demonstrated attenuation of the elevation of both inflammation-related gene expression and proinflammatory cytokines and chemokines, leukocyte infiltration, and MAPK and signal transducer and activator of transcription 3 activation...
May 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28522593/small-gtpase-rab1b-is-associated-with-atg9a-vesicles-and-regulates-autophagosome-formation
#4
Soichiro Kakuta, Junji Yamaguchi, Chigure Suzuki, Mitsuho Sasaki, Saiko Kazuno, Yasuo Uchiyama
ATG9 is a membrane protein that is essential for autophagy and is considered to be directly involved in the early steps of autophagosome formation. Yeast Atg9 is mainly localized to small vesicles (Atg9 vesicles), whereas mammalian ATG9A is reportedly localized to the trans-Golgi network, the endosomal compartment, and other unidentified membrane structures. To dissect the ATG9A-containing membranes, we examined the subcellular localization of ATG9A and performed immunoisolation of those membranes. ATG9A-green fluorescent protein in human culture cells was observed as numerous puncta that move rapidly throughout the cytoplasm...
May 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28515154/progerin-sequestration-of-pcna-promotes-replication-fork-collapse-and-mislocalization-of-xpa-in-laminopathy-related-progeroid-syndromes
#5
Benjamin A Hilton, Ji Liu, Brian M Cartwright, Yiyong Liu, Maya Breitman, Youjie Wang, Rowdy Jones, Hui Tang, Antonio Rusinol, Phillip R Musich, Yue Zou
Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder that is caused by a point mutation in the LMNA gene resulting in production of a truncated farnesylated-prelamin A protein (progerin). We previously reported that XPA mislocalized to the progerin-induced DNA double-strand break (DSB) sites, blocking DSB repair, which led to DSB accumulation, DNA damage responses, and early replication arrest in HGPS. In this study, the XPA mislocalization to DSBs occurred at stalled or collapsed replication forks, concurrent with a significant loss of PCNA at the forks, whereas PCNA efficiently bound to progerin...
May 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28515153/differential-regulation-of-renal-klotho-and-fgfr1-in-normal-and-uremic-rats
#6
Juan R Muñoz-Castañeda, Carmen Herencia, Maria Victoria Pendón-Ruiz de Mier, Maria Encarnación Rodriguez-Ortiz, Juan M Diaz-Tocados, Noemi Vergara, Julio M Martínez-Moreno, Maria Dolores Salmerón, William G Richards, Arnold Felsenfeld, Makoto Kuro-O, Yolanda Almadén, Mariano Rodríguez
In renal failure, hyperphosphatemia occurs despite a marked elevation in serum fibroblast growth factor (FGF)-23. Abnormal regulation of the FGFR1-Klotho receptor complex may cause a resistance to the phosphaturic action of FGF23. The purpose of the present study was to investigate the regulation of renal Klotho and FGF receptor (FEFR)-1 in healthy and uremic rats induced by 5/6 nephrectomy. In normal rats, the infusion of rat recombinant FGF23 enhanced phosphaturia and increased renal FGFR1 expression; however, Klotho expression was reduced...
May 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28515152/effects-of-deficiency-of-kelch-like-ech-associated-protein-1-on-skeletal-organization-a-mechanism-for-diminished-nuclear-factor-of-activated-t-cells-cytoplasmic-1-during-osteoclastogenesis
#7
Eiko Sakai, Masanobu Morita, Masahiro Ohuchi, Mizuho A Kido, Yutaka Fukuma, Kazuhisa Nishishita, Kuniaki Okamoto, Ken Itoh, Masayuki Yamamoto, Takayuki Tsukuba
Kelch-like ECH-associated protein 1 (Keap1) binds to nuclear factor E2 p45-related factor 2 (Nrf2), a transcription factor for antioxidant enzymes, to suppress Nrf2 activation. The role of oxidative stress in many diseases supports the possibility that processes that are associated with Nrf2 activation might offer therapeutic potential. Nrf2 deficiency induces osteoclastogenesis, which is responsible for bone loss, by activating receptor activator of NF-κB ligand (RANKL)-mediated signaling; however, the effects of Keap1 deficiency remain unclear...
May 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28515151/assessing-the-satisfaction-and-burden-within-an-academic-animal-care-and-use-program
#8
John N Norton, Randall P Reynolds, Cliburn Chan, Raphael H Valdivia, Herman F Staats
Although animal research requires adherence to various regulations and standards, the manner in which compliance is maintained and the degree of additional constraints varies between institutions. Regulatory burden, particularly if institutionally imposed, has become a concern for institutions as increased regulatory expectations result in decreased resources available for research efforts. Faculty, research staff, and support staff engaged in animal research were surveyed to determine what Institutional Animal Care and Use Committee (IACUC) processes were considered burdensome, the perceived value of some suggested modifications, and satisfaction with the IACUC Administrative Office and the animal resource unit...
May 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28515150/receptor-for-advanced-glycation-end-products-is-targeted-by-fbxo10-for-ubiquitination-and-degradation
#9
John Evankovich, Travis Lear, Alison Mckelvey, Sarah Dunn, James Londino, Yuan Liu, Bill B Chen, Rama K Mallampalli
The receptor for advanced glycation end products (RAGE) is a highly expressed cell membrane receptor serving to anchor lung epithelia to matrix components, and it also amplifies inflammatory signaling during acute lung injury. However, mechanisms that regulate its protein concentrations in cells remain largely unknown. Here we show that RAGE exhibits an extended life span in lung epithelia (t½ 6 h), is monoubiquitinated at K374, and is degraded in lysosomes. The RAGE ligand ODN2006, a synthetic oligodeoxynucleotide resembling pathogenic hypomethylated CpG DNA, promotes rapid lysosomal RAGE degradation through activation of protein kinase C zeta (PKCζ), which phosphorylates RAGE...
May 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28512191/mir-2392-suppresses-metastasis-and-epithelial-mesenchymal-transition-by-targeting-maml3-and-whsc1-in-gastric-cancer
#10
Jinjing Li, Tingyu Li, Yuanyuan Lu, Gaofei Shen, Hao Guo, Jian Wu, Chao Lei, Feng Du, Fenli Zhou, Xiaodi Zhao, Yongzhan Nie, Daiming Fan
MicroRNAs have emerged as essential regulators of various cellular processes. We identified the role and underlying mechanisms of miR-2392 in gastric cancer (GC) metastasis. miR-2392 was down-regulated in GC cell lines and tissues, and overexpression of miR-2392 significantly inhibited GC invasion and metastasis in vitro and in vivo We identified MAML3 and WHSC1 as novel targets of miR-2392, and knockdown of MAML3 and WHSC1 had the same antimetastatic effect as that of miR-2392 in GC cells. These effects were clinically relevant, as low miR-2392 expression was correlated with high MAML3 and WHSC1 expression and poor survival in patients with GC...
May 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28507169/human-neutrophil-elastase-induces-endothelial-cell-apoptosis-by-activating-the-perk-chop-branch-of-the-unfolded-protein-response
#11
Irina Grechowa, Sven Horke, Anja Wallrath, Christian-Friedrich Vahl, Bernhard Dorweiler
Human neutrophil elastase impacts on atherosclerotic plaque stability by inducing apoptosis in endothelial cells. Our aim was to investigate the proapoptotic mechanism of elastase on endothelial cells and to evaluate the presence of elastase in human plaque material. Human endothelial cells were treated with purified human neutrophil elastase. Apoptosis was assayed by capsase-3/7 activation, TUNEL, and sub-G1 assay. Activation of unfolded protein response (UPR) effector molecules binding Ig protein, soluble X-binding protein-1, protein kinase RNA-like ER kinase (PERK), and C/EBP-homologous protein (CHOP) was analyzed by RT-PCR, immunocytochemistry, and Western blot...
May 15, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28507168/nutritional-interventions-and-the-il-6-response-to-exercise
#12
REVIEW
Stephen R Hennigar, James P McClung, Stefan M Pasiakos
IL-6 is a pleiotropic cytokine with a wide range of biologic effects. In response to prolonged exercise, IL-6 is synthesized by contracting skeletal muscle and released into circulation. Circulating IL-6 is thought to maintain energy status during exercise by acting as an energy sensor for contracting muscle and stimulating glucose production. If tissue damage occurs, immune cells infiltrate and secrete cytokines, including IL-6, to repair skeletal muscle damage. With adequate rest and nutrition, the IL-6 response to exercise is attenuated as skeletal muscle adapts to training...
May 15, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28495756/cystic-fibrosis-transmembrane-conductance-regulator-mediates-tenogenic-differentiation-of-tendon-derived-stem-cells-and-tendon-repair-accelerating-tendon-injury-healing-by-intervening-in-its-downstream-signaling
#13
Yang Liu, Jia Xu, Liangliang Xu, Tianyi Wu, Yuxin Sun, Yuk-Wai Lee, Bin Wang, Hsiao-Chang Chan, Xiaohua Jiang, Jinfang Zhang, Gang Li
Tendons are a mechanosensitive tissue, which enables them to transmit to bone forces that are derived from muscle. Patients with tendon injuries, such as tendinopathy or tendon rupture, were often observed with matrix degeneration, and the healing of tendon injuries remains a challenge as a result of the limited understanding of tendon biology. Our study demonstrates that the stretch-mediated activation channel, cystic fibrosis transmembrane conductance regulator (CFTR), was up-regulated in tendon-derived stem cells (TDSCs) during tenogenic differentiation under mechanical stretching...
May 11, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28495755/intestinal-microbiota-contributes-to-colonic-epithelial-changes-in-simulated-microgravity-mouse-model
#14
Junxiu Shi, Yifan Wang, Jian He, Pingping Li, Rong Jin, Ke Wang, Xi Xu, Jie Hao, Yan Zhang, Hongju Liu, Xiaoping Chen, Hounan Wu, Qing Ge
Exposure to microgravity leads to alterations in multiple systems, but microgravity-related changes in the gastrointestinal tract and its clinical significance have not been well studied. We used the hindlimb unloading (HU) mouse model to simulate a microgravity condition and investigated the changes in intestinal microbiota and colonic epithelial cells. Compared with ground controls (Ctrls), HU affected fecal microbiota composition with a profile that was characterized by the expansion of Firmicutes and decrease of Bacteroidetes The colon epithelium of HU mice showed decreased goblet cell numbers, reduced epithelial cell turnover, and decreased expression of genes that are involved in defense and inflammatory responses...
May 11, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28495754/phd3-is-a-transcriptional-coactivator-of-hif-1%C3%AE-in-nucleus-pulposus-cells-independent-of-the-pkm2-jmjd5-axis
#15
Zachary R Schoepflin, Elizabeth S Silagi, Irving M Shapiro, Makarand V Risbud
The role of prolyl hydroxylase (PHD)-3 as a hypoxia inducible factor (HIF)-1α cofactor is controversial and remains unknown in skeletal tissues. We investigated whether PHD3 controls HIF-1 transcriptional activity in nucleus pulposus (NP) cells through the pyruvate kinase muscle (PKM)-2-Jumonji domain--containing protein (JMJD5) axis. PHD3(-/-) mice (12.5 mo old) showed increased incidence of intervertebral disc degeneration with a concomitant decrease in expression of the HIF-1α targets VEGF-A, glucose transporter-1, and lactate dehydrogenase A...
May 11, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28490483/the-ratio-of-dihomo-%C3%AE-linolenic-acid-to-deoxycholic-acid-species-is-a-potential-biomarker-for-the-metabolic-abnormalities-in-obesity
#16
Sha Lei, Fengjie Huang, Aihua Zhao, Tianlu Chen, Wenlian Chen, Guoxiang Xie, Xiaojiao Zheng, Yunjing Zhang, Haoyong Yu, Pin Zhang, Cynthia Rajani, Yuqian Bao, Weiping Jia, Wei Jia
Bile acid (BA) signaling regulates fatty acid metabolism. BA dysregulation plays an important role in the development of metabolic disease. However, BAs in relation to fatty acids have not been fully investigated in obesity (OB)-related metabolic disorders. A targeted metabolomic measurement of serum BA and free fatty acid profiles was applied to sera of 381 individuals in 2 independent studies. The results showed that the ratio of dihomo-γ-linolenic acid (DGLA) to DCA species (DCAs) was significantly increased in OB individuals with type 2 diabetes (T2DM) from a case-control study and decreased in the remission group of OB subjects with T2DM after metabolic surgery...
May 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28490482/conditional-ablation-of-raptor-in-the-male-germ-line-causes-infertility-due-to-meiotic-arrest-and-impaired-inactivation-of-sex-chromosomes
#17
Mengneng Xiong, Zhiping Zhu, Suwen Tian, Ruping Zhu, Shun Bai, Kaiqiang Fu, James G Davis, Zheng Sun, Joseph A Baur, Ke Zheng, Lan Ye
Rapamycin is a clinically important drug that is used in transplantation and cancer therapy but which causes a number of side effects, including male infertility. Its canonical target, mammalian target of rapamycin complex 1 (mTORC1), plays a key role in metabolism and binds chromatin; however, its precise role in the male germ line has not been elucidated. Here, we inactivate the core component, Raptor, to show that mTORC1 function is critical for male meiosis and the inactivation of sex chromosomes. Disruption of the Raptor gene impairs chromosomal synapsis and prevents the efficient spreading of silencing factors into the XY chromatin...
May 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28487283/bile-acids-deoxycholic-acid-and-ursodeoxycholic-acid-differentially-regulate-human-%C3%AE-defensin-1-and-2-secretion-by-colonic-epithelial-cells
#18
Natalia K Lajczak, Vinciane Saint-Criq, Aoife M O'Dwyer, Alessia Perino, Luciano Adorini, Kristina Schoonjans, Stephen J Keely
Bile acids and epithelial-derived human β-defensins (HβDs) are known to be important factors in the regulation of colonic mucosal barrier function and inflammation. We hypothesized that bile acids regulate colonic HβD expression and aimed to test this by investigating the effects of deoxycholic acid (DCA) and ursodeoxycholic acid on the expression and release of HβD1 and HβD2 from colonic epithelial cells and mucosal tissues. DCA (10-150 µM) stimulated the release of both HβD1 and HβD2 from epithelial cell monolayers and human colonic mucosal tissue in vitro In contrast, ursodeoxycholic acid (50-200 µM) inhibited both basal and DCA-induced defensin release...
May 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28487282/regulation-of-spermatogenesis-by-a-local-functional-axis-in-the-testis-role-of-the-basement-membrane-derived-noncollagenous-1-domain-peptide
#19
Haiqi Chen, Dolores D Mruk, Will M Lee, C Yan Cheng
Spermatogenesis takes place in the epithelium of the seminiferous tubules of the testes, producing millions of spermatozoa per day in an adult male in rodents and humans. Thus, multiple cellular events that are regulated by an array of signaling molecules and pathways are tightly coordinated to support spermatogenesis. Here, we report findings of a local regulatory axis between the basement membrane (BM), the blood-testis barrier (BTB), and the apical ectoplasmic specialization (apical ES; a testis-specific, actin-rich adherens junction at the Sertoli cell-spermatid interface) to coordinate cellular events across the seminiferous epithelium during the epithelial cycle...
May 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28487281/filamin-a-is-required-for-spindle-migration-and-asymmetric-division-in-mouse-oocytes
#20
HaiYang Wang, Jing Guo, ZiLi Lin, Suk Namgoong, Jeong Su Oh, Nam-Hyung Kim
Dynamic changes in the actin network are crucial for the cortical migration of spindles and establishment of polarity, to ensure asymmetric division during meiotic maturation. In this study, filamin A (FLNA) was found to be an essential actin regulator that controlled spindle migration and asymmetric division during oocyte meiosis. FLNA was localized in the cytoplasm and enriched at the cortex and near the chromosomes. Knockdown of FLNA impaired meiotic asymmetric division and spindle migration with a decrease in the amount of cytoplasmic actin mesh and cortical actin levels...
May 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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