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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/28928248/carbonic-anhydrase-iii-protects-osteocytes-from-oxidative-stress
#1
Chao Shi, Yuhei Uda, Christopher Dedic, Ehab Azab, Ningyuan Sun, Amira I Hussein, Christopher A Petty, Keertik Fulzele, Maria C Mitterberger-Vogt, Werner Zwerschke, Renata Pereira, Kunzheng Wang, Paola Divieti Pajevic
Osteocytes are master orchestrators of bone remodeling; they control osteoblast and osteoclast activities both directly via cell-to-cell communication and indirectly via secreted factors, and they are the main postnatal source of sclerostin and RANKL (receptor activator of NF-kB ligand), two regulators of osteoblast and osteoclast function. Despite progress in understanding osteocyte biology and function, much remains to be elucidated. Recently developed osteocytic cell lines-together with new genome editing tools-has allowed a closer look at the biology and molecular makeup of these cells...
September 19, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28928247/endogenous-glucocorticoid-signaling-in-chondrocytes-attenuates-joint-inflammation-and-damage
#2
Jinwen Tu, Shihani Stoner, Phillip D Fromm, Tingyu Wang, Di Chen, Jan Tuckermann, Mark S Cooper, Markus J Seibel, Hong Zhou
Previous studies demonstrated that endogenous glucocorticoid signaling in osteoblasts promotes inflammation in murine immune arthritis. The current study determined whether disruption of endogenous glucocorticoid signaling in chondrocytes also modulates the course and severity of arthritis. Tamoxifen-inducible chondrocyte-targeted glucocorticoid receptor knockout (chGRKO) mice were generated by breeding GR(flox/flox) mice with tamoxifen-inducible Collagen 2a1 Cre mice (Col2a1-CreER(T2)). Antigen-induced arthritis (AIA) and K/BxN serum transfer-induced arthritis (STIA) were induced in both chGRKO mice and their Cre-negative GR(flox/flox) littermates [wild type (WT)]...
September 19, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28928246/exploiting-mitochondrial-and-oxidative-vulnerabilities-with-a-synthetic-analog-of-pancratistatin-in-combination-with-piperlongumine-for-cancer-therapy
#3
Dennis Ma, Tyler Gilbert, Christopher Pignanelli, Daniel Tarade, Megan Noel, Fadi Mansour, Manika Gupta, Sabrina Ma, Jesse Ropat, Colin Curran, Sergey Vshyvenko, Tomas Hudlicky, Siyaram Pandey
Harsh adverse effects as a result of nonspecific targeting of chemotherapeutics currently pose obstacles in cancer therapy; thus, it would be invaluable to devise novel approaches to specifically target cancer cells. The natural compound pancratistatin (PST) has been shown to preferentially induce apoptosis in a variety of cancer cell types. Recently, several analogs of PST were shown to be efficacious in inducing apoptosis in a variety of aggressive cancer cell types via cancer cell mitochondrial targeting; it caused dissipation of mitochondrial membrane potential and decreased oxygen consumption, and with isolated mitochondria, it induced the release of apoptogenic factors...
September 19, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28928245/evi-and-mds-evi-are-required-for-adult-intestinal-stem-cell-formation-during-postembryonic-vertebrate-development
#4
Morihiro Okada, Yun-Bo Shi
The gene ectopic viral integration site 1 (EVI) and its variant myelodysplastic syndrome 1 (MDS)/EVI encode zinc-finger proteins that have been recognized as important oncogenes in various types of cancer. In contrast to the established role of EVI and MDS/EVI in cancer development, their potential function during vertebrate postembryonic development, especially in organ-specific adult stem cells, is unclear. Amphibian metamorphosis is strikingly similar to postembryonic development around birth in mammals, with both processes taking place when plasma thyroid hormone (T3) levels are high...
September 19, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28928244/selective-inhibitory-effects-of-zinc-on-cell-proliferation-in-esophageal-squamous-cell-carcinoma-through-orai1
#5
Sangyong Choi, Chaochu Cui, Yanhong Luo, Sun-Hee Kim, Jae-Kyun Ko, Xiaofang Huo, Jianjie Ma, Li-Wu Fu, Rhonda F Souza, Irina Korichneva, Zui Pan
Zinc, an essential micronutrient, has a cancer preventive role. Zinc deficiency has been shown to contribute to the progression of esophageal cancer. Orai1, a store-operated Ca(2+) entry (SOCE) channel, was previously reported to be highly expressed in tumor tissues removed from patients with esophageal squamous cell carcinoma (ESCC) with poor prognosis, and elevation of its expression contributes to both hyperactive intracellular Ca(2+) oscillations and fast cell proliferation in human ESCC cells. However, the molecular basis of cancer preventive functions of zinc and its association with Orai1-mediated cell proliferation remains unknown...
September 19, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28904023/%C3%AE-linolenic-acid-derived-metabolites-from-gut-lactic-acid-bacteria-induce-differentiation-of-anti-inflammatory-m2-macrophages-through-g-protein-coupled-receptor-40
#6
Ryuji Ohue-Kitano, Yumiko Yasuoka, Tsuyoshi Goto, Nahoko Kitamura, Si-Bum Park, Shigenobu Kishino, Ikuo Kimura, Mayu Kasubuchi, Haruya Takahashi, Yongjia Li, Yu-Sheng Yeh, Huei-Fen Jheng, Mari Iwase, Masashi Tanaka, Shinya Masuda, Takayuki Inoue, Hajime Yamakage, Toru Kusakabe, Fumito Tani, Akira Shimatsu, Nobuyuki Takahashi, Jun Ogawa, Noriko Satoh-Asahara, Teruo Kawada
Among dietary fatty acids with immunologic effects, ω-3 polyunsaturated fatty acids, such as α-linolenic acid (ALA), have been considered as factors that contribute to the differentiation of M2-type macrophages (M2 macrophages). 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...
September 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28904022/pi3k%C3%AE-ablation-does-not-promote-diabetes-in-db-db-mice-but-improves-insulin-sensitivity-and-reduces-pancreatic-%C3%AE-cell-apoptosis
#7
Ludovic Breasson, Claudia Sardi, Barbara Becattini, Fabio Zani, Giovanni Solinas
PI3Kγ has emerged as a promising target for the treatment of obesity and insulin resistance; however, previous studies have indicated that PI3Kγ 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 PI3Kγ. To address this issue, we investigated the effects of PI3Kγ ablation in db/db diabetic mice, a genetic model of obesity-driven β-cell failure and diabetes...
September 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28904021/bap-exposure-causes-oocyte-meiotic-arrest-and-fertilization-failure-to-weaken-female-fertility
#8
Mianqun Zhang, Yilong Miao, Qian Chen, Meng Cai, Wenkang Dong, Xiaoxin Dai, Yajuan Lu, Changyin Zhou, Zhaokang Cui, Bo Xiong
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, chromosome alignment, and kinetochore-microtubule attachment, consequently leading to the generation of aneuploid eggs...
September 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28904020/gtrap3-18-regulates-food-intake-and-body-weight-by-interacting-with-pro-opiomelanocortin
#9
Koji Aoyama, Wattanaporn Bhadhprasit, Masahiko Watabe, Fan Wang, Nobuko Matsumura, Toshio Nakaki
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 regulator of food intake and body weight by interacting with POMC...
September 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28904019/cathepsin-b-mediated-cd18-shedding-regulates-leukocyte-recruitment-from-angiogenic-vessels
#10
Shintaro Nakao, Souska Zandi, Dawei Sun, Ali Hafezi-Moghadam
Cathepsin B (CtsB) contributes to atherosclerosis and cancer progression by processing the extracellular matrix and promoting angiogenesis. Although CtsB was reported to promote and reduce angiogenesis, there is no mechanistic explanation that reconciles this apparent discrepancy. CtsB cleaves CD18 from the surface of immune cells, but its contribution to angiogenesis has not been studied. We developed an in vivo technique for visualization of immune cell transmigration from corneal vessels toward implanted cytokines...
September 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28904018/dyslipidemia-impairs-mitochondrial-trafficking-and-function-in-sensory-neurons
#11
Amy E Rumora, Stephen I Lentz, Lucy M Hinder, Samuel W Jackson, Andrew Valesano, Gideon E Levinson, Eva L Feldman
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 palmitate and glucose and assessed for alterations in mitochondrial trafficking, mitochondrial membrane potential, and mitochondrial bioenergetics...
September 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28904017/eliciting-improved-antibacterial-efficacy-of-host-proteins-in-the-presence-of-antibiotics
#12
Joanna Jammal, Fadia Zaknoon, Amram Mor
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...
September 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28904016/lncrna-ak017368-promotes-proliferation-and-suppresses-differentiation-of-myoblasts-in-skeletal-muscle-development-by-attenuating-the-function-of-mir-30c
#13
Tingting Liang, Bo Zhou, Lei Shi, Han Wang, Qingpo Chu, Feilong Xu, Yuan Li, Ruonan Chen, Chunyan Shen, Allan P Schinckel
Long noncoding RNAs (lncRNAs) have been reported to play diverse roles in biologic and pathologic processes, including myogenesis. We found that lncRNA AK017368 is highly expressed in skeletal muscle cells. Functional analyses showed that overexpression of AK017368 promoted proliferation and restrained differentiation of myoblasts; whereas inhibition of AK017368 had completely opposite effects in vitro In mice, knockdown of AK017368 promoted muscle hypertrophy in vivo RNA molecules of AK017368 acted mechanistically as competing endogenous RNAs to target micro-RNA (miR)-30c, which was supported by the results of bioinformatics analyses and dual-luciferase reporter assays...
September 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28899881/tet1-overexpression-leads-to-anxiety-like-behavior-and-enhanced-fear-memories-via-the-activation-of-calcium-dependent-cascade-through-egr1-expression-in-mice
#14
Wookbong Kwon, Hyeng-Soo Kim, Jain Jeong, Yonghun Sung, Minjee Choi, Song Park, Jinhee Lee, Soyoung Jang, Sung Hyun Kim, Sanggyu Lee, Myoung Ok Kim, Zae Young Ryoo
Ten-eleven translocation methylcytosine dioxygenase 1 (Tet1) initiates DNA demethylation by converting 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) at CpG-rich regions of genes, which have key roles in adult neurogenesis and memory. In addition, the overexpression of Tet1 with 5-hmC alteration in patients with psychosis has also been reported, for instance in schizophrenia and bipolar disorders. The mechanism underlying Tet1 overexpression in the brain; however, is still elusive. In the present study, we found that Tet1-transgenic (Tet1-TG) mice displayed abnormal behaviors involving elevated anxiety and enhanced fear memories...
September 12, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28899880/effects-of-aging-and-resistance-training-in-rat-tendon-remodeling
#15
Rita C Marqueti, João L Q Durigan, Anderson José S Oliveira, Marcelo Shinyu Mekaro, Vinicius Guzzoni, Andrea A Aro, Edson Rosa Pimentel, Heloisa S Selistre-de-Araujo
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...
September 12, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28899879/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
#16
Amy J Hector, Chris McGlory, Felipe Damas, Nicole Mazara, Steven K Baker, Stuart M Phillips
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/m(2); age 22 ± 1 yr) underwent 10 d of 40%-reduced energy intake while performing unilateral resistance exercise and consuming lower protein (1...
September 12, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28899878/endothelial-cells-promote-triple-negative-breast-cancer-cell-metastasis-via-pai-1-and-ccl5-signaling
#17
Wenwen Zhang, Jing Xu, Hehui Fang, Lin Tang, Weiwei Chen, Qian Sun, Qun Zhang, Fang Yang, Zijia Sun, Lulu Cao, Yucai Wang, Xiaoxiang Guan
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 stimulate the expression and secretion of the chemokine, CCL5, from ECs, which then acts in a paracrine fashion on TNBC cells to enhance their migration, invasion, and metastasis...
September 12, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28883043/ffar2-ffar3-receptor-heteromerization-modulates-short-chain-fatty-acid-sensing
#18
Zhiwei Ang, Ding Xiong, Min Wu, Jeak Ling Ding
Free fatty acid receptors (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...
September 7, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28883042/real-time-acquisition-of-transendothelial-electrical-resistance-in-an-all-human-in-vitro-3-dimensional-blood-brain-barrier-model-exemplifies-tight-junction-integrity
#19
Zaynah Maherally, Helen L Fillmore, Sim Ling Tan, Suk Fei Tan, Samah A Jassam, Friederike I Quack, Kathryn E Hatherell, Geoffrey J Pilkington
The blood-brain barrier (BBB) consists of endothelial cells, astrocytes, and pericytes embedded in basal lamina (BL). Most in vitro models use nonhuman, monolayer cultures for therapeutic-delivery studies, relying on transendothelial electrical resistance (TEER) measurements without other tight-junction (TJ) formation parameters. We aimed to develop reliable, reproducible, in vitro 3-dimensional (3D) models incorporating relevant human, in vivo cell types and BL proteins. The 3D BBB models were constructed with human brain endothelial cells, human astrocytes, and human brain pericytes in mono-, co-, and tricultures...
September 7, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28883041/normoxic-cells-remotely-regulate-the-acid-base-balance-of-cells-at-the-hypoxic-core-of-connexin-coupled-tumor-growths
#20
Tobias H Dovmark, Alzbeta Hulikova, Steven A Niederer, Richard D Vaughan-Jones, Pawel Swietach
ATP fuels the removal of metabolic end-products, including H(+) ions that profoundly modulate biological activities. Energetic resources in hypoxic tumor regions are constrained by low-yielding glycolysis, and any means of reducing the cost of acid extrusion, without compromising pH homeostasis, would therefore be advantageous for cancer cells. Some cancers express connexin channels that allow solute exchange between cells, and we propose that, via this route, normoxic cells supply hypoxic neighbors with acid-neutralizing HCO3(-) ions...
September 7, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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