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

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https://read.qxmd.com/read/30786218/maspin-binds-to-cardiolipin-in-mitochondria-and-triggers-apoptosis
#1
Nitin Mahajan, Brandon Hoover, Manohary Rajendram, Heidi Y Shi, Kiyoshi Kawasaki, Douglas B Weibel, Ming Zhang
A central question in cell biology is how cells respond to stress signals and biochemically regulate apoptosis. One critical pathway involves the change of mitochondrial function and release of cytochrome c to initiate apoptosis. In response to apoptotic stimuli, we found that maspin-a noninhibitory member of the serine protease inhibitor superfamily-translocates from the cytosol to mitochondria and binds to cardiolipin in the inner mitochondrial membrane. Biolayer interferometry assay revealed that recombinant maspin binds cardiolipin with an apparent Kd ,of ∼15...
February 20, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/30785802/high-glucose-induced-ubiquitination-of-g6pd-leads-to-the-injury-of-podocytes
#2
Meng Wang, Ji Hu, Linling Yan, Yeping Yang, Min He, Meng Wu, Qin Li, Wei Gong, Yang Yang, Yi Wang, Diane E Handy, Bin Lu, Chuanming Hao, Qinghua Wang, Yiming Li, Ronggui Hu, Robert C Stanton, Zhaoyun Zhang
Oxidative stress contributes substantially to podocyte injury, which plays an important role in the development of diabetic kidney disease. The mechanism of hyperglycemia-induced oxidative stress in podocytes is not fully understood. Glucose-6-phosphate dehydrogenase (G6PD) is critical in maintaining NADPH, which is an important cofactor for the antioxidant system. Here, we hypothesized that high glucose induced ubiquitination and degradation of G6PD, which injured podocytes by reactive oxygen species (ROS) accumulation...
February 20, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/30785766/the-activity-of-transient-receptor-potential-channel-c-6-modulates-the-differentiation-of-fat-cells
#3
Yan Qin Tan, Hiu Yee Kwan, Xiaoqiang Yao, Lai K Leung
Previously, the V1-3 isoforms of the transient receptor potential channel (TRP) have been shown to promote or prevent adipocyte differentiation. In the current study, the C isoforms were screened for blocking adipogenesis. The hypothesis that the TRP classic or canonical (TRPC) deters adipocyte differentiation was investigated in 3T3-L1 cells employing the channel-specific activator and antagonist, silencing, and overexpression techniques. Fat accumulation in cells was visualized by Oil Red O staining. Intracellular calcium inflow was estimated by confocal microscopy...
February 20, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/30779881/loss-of-growth-hormone-mediated-signal-transducer-and-activator-of-transcription-5-stat5-signaling-in-mice-results-in-insulin-sensitivity-with-obesity
#4
Yash Chhabra, Caroline N Nelson, Monika Plescher, Johanna L Barclay, Aaron G Smith, Sof Andrikopoulos, Salvatore Mangiafico, David J Waxman, Andrew J Brooks, Michael J Waters
Growth hormone (GH) has an important function as an insulin antagonist with elevated insulin sensitivity evident in humans and mice lacking a functional GH receptor (GHR). We sought the molecular basis for this sensitivity by utilizing a panel of mice possessing specific deletions of GHR signaling pathways. Metabolic clamps and glucose homeostasis tests were undertaken in these obese adult C57BL/6 male mice, which indicated impaired hepatic gluconeogenesis. Insulin sensitivity and glucose disappearance rate were enhanced in muscle and adipose of mice lacking the ability to activate the signal transducer and activator of transcription (STAT)5 via the GHR ( Ghr-391 -/- ) as for GHR-null ( GHR-/- ) mice...
February 19, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/30779601/unravelling-the-transcriptional-responses-of-tgf-%C3%AE-smad3-and-ezh2-constitute-a-regulatory-switch-that-controls-neuroretinal-epithelial-cell-fate-specification
#5
Darrell Andrews, Giorgio Oliviero, Letizia De Chiara, Ariane Watson, Emily Rochford, Kieran Wynne, Ciaran Kennedy, Shane Clerkin, Benjamin Doyle, Catherine Godson, Paul Connell, Colm O'Brien, Gerard Cagney, John Crean
Cell differentiation is directed by extracellular cues and intrinsic epigenetic modifications, which control chromatin organization and transcriptional activation. Central to this process is PRC2, which modulates the di- and trimethylation of lysine 27 on histone 3; however, little is known concerning the direction of PRC2 to specific loci. Here, we have investigated the physical interactome of EZH2, the enzymatic core of PRC2, during retinoic acid-mediated differentiation of neuroepithelial, pluripotent NT2 cells and the dedifferentiation of neuroretinal epithelial ARPE19 cells in response to TGF-β...
February 19, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/30776318/ceria-nanoparticles-enhance-endochondral-ossification-based-critical-sized-bone-defect-regeneration-by-promoting-the-hypertrophic-differentiation-of-bmscs-via-dhx15-activation
#6
Jianmei Li, Fei Kang, Xiaoshan Gong, Yun Bai, Jingjin Dai, Chunrong Zhao, Ce Dou, Zhen Cao, Mengmeng Liang, Rui Dong, Hong Jiang, Xiaochao Yang, Shiwu Dong
Central ischemic necrosis is one of the biggest obstacles in the clinical application of traditional tissue-engineered bone (TEB) in critical-sized bone defect regeneration. Because of its ability to promote vascular invasion, endochondral ossification-based TEB has been applied for bone defect regeneration. However, inadequate chondrocyte hypertrophy can hinder vascular invasion and matrix mineralization during endochondral ossification. In light of recent studies suggesting that ceria nanoparticles (CNPs) improve the blood vessel distribution within TEB, we modified TEB scaffold surfaces with CNPs and investigated the effect and mechanism of CNPs on endochondral ossification-based bone regeneration...
February 18, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/30776316/atp-redirects-cytokine-trafficking-and-promotes-novel-membrane-tnf-signaling-via-microvesicles
#7
Sanooj Soni, Kieran P O'Dea, Ying Ying Tan, Kahori Cho, Eiko Abe, Rosalba Romano, Jiang Cui, Daqing Ma, Padmini Sarathchandra, Michael R Wilson, Masao Takata
Cellular stress or injury induces release of endogenous danger signals such as ATP, which plays a central role in activating immune cells. ATP is essential for the release of nonclassically secreted cytokines such as IL-1β but, paradoxically, has been reported to inhibit the release of classically secreted cytokines such as TNF. Here, we reveal that ATP does switch off soluble TNF (17 kDa) release from LPS-treated macrophages, but rather than inhibiting the entire TNF secretion, ATP packages membrane TNF (26 kDa) within microvesicles (MVs)...
February 18, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/30776251/trophoblastic-proliferation-and-invasion-regulated-by-actn4-is-impaired-in-early-onset-preeclampsia
#8
Wei Peng, Chao Tong, Lei Li, Chengyu Huang, Yuxin Ran, Xuehai Chen, Yuxiang Bai, Yamin Liu, Jianlin Zhao, Bin Tan, Xiaofang Luo, Hao Wang, Li Wen, Chen Zhang, Hua Zhang, Yubin Ding, Hongbo Qi, Philip N Baker
Successful pregnancy requires normal placentation, which largely depends on the tight regulation of proliferation, invasion, and migration of trophoblast cells. Abnormal functioning of trophoblast cells may cause failure of uterine spiral artery remodeling, which may be related to pregnancy-related disorders, such as preeclampsia. Here, we reported that an actin-binding protein, α-actinin (ACTN)4, was dysregulated in placentas from early onset preeclampsia. Moreover, knockdown of ACTN4 markedly inhibited trophoblast cell proliferation by reducing AKT membrane translocation...
February 18, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/30776250/transactivation-domain-of-kr%C3%A3-ppel-like-factor-15-negatively-regulates-angiotensin-ii-induced-adventitial-inflammation-and-fibrosis
#9
Yuan-Yuan Lu, Xiao-Dong Li, Han-Dan Zhou, Shuai Shao, Shun He, Mo-Na Hong, Jia-Chen Liu, Ying-Le Xu, Yong-Jie Wu, Ding-Liang Zhu, Ji-Guang Wang, Ping-Jin Gao
Krüppel-like factor (KLF) 15 has emerged as a critical regulator of fibrosis in cardiovascular diseases. However, the precise role that KLF15 and its functional domain played in adventitial inflammation and fibrosis remains unclear. This study aims to investigate the role of the transactivation domain (TAD) of KLF15 in angiotensin II (Ang II)-induced adventitial pathologic changes. KLF15 expression was decreased in the vascular adventitia of Ang II-infused mice (1000 ng/kg/min, 14 d) and in adventitial fibroblasts (AFs) stimulated by Ang II (10-7 M)...
February 18, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/30768374/aquaporin-3-deficiency-slows-cyst-enlargement-in-experimental-mouse-models-of-autosomal-dominant-polycystic-kidney-disease
#10
Weiling Wang, Xiaoqiang Geng, Lei Lei, Yingli Jia, Yingjie Li, Hong Zhou, Alan S Verkman, Baoxue Yang
Human autosomal dominant polycystic kidney disease (ADPKD) is characterized by bilateral renal cysts that lead to a decline in kidney function. Previous studies reported aquaporin (AQP)-3 expression in cysts derived from collecting ducts in ADPKD. To study the role of AQP3 in cyst development, we generated 2 polycystic kidney disease (PKD) mouse models: kidney-specific Pkd1 knockout mice and inducible Pkd1 knockout mice, each without and with AQP3 deletion. In both models, kidney sizes and cyst indexes were significantly reduced in AQP3-null PKD mice compared with AQP3-expressing PKD mice, with the difference seen mainly in collecting duct cysts...
February 15, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/30768370/talin-promotes-integrin-activation-accompanied-by-generation-of-tension-in-talin-and-an-increase-in-osmotic-pressure-in-neurite-outgrowth
#11
Yifan Wang, Xiaolong Zhang, Jilai Tian, Jinjun Shan, Yunfeng Hu, Yiqian Zhai, Jun Guo
Neuronal polarization depends on the interaction of intracellular chemical and mechanical activities in which the cytoplasmic protein, talin, plays a pivotal role during neurite growth. To better understand the mechanism underlying talin function in neuronal polarization, we overexpressed several truncated forms of talin and found that the presence of the rod domain within the overexpressed talin is required for its positive effect on neurite elongation because the neurite number only increased when the talin head region was overexpressed...
February 15, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/30768368/paternal-high-fat-diet-transgenerationally-impacts-hepatic-immunometabolism
#12
Thais de Castro Barbosa, Petter S Alm, Anna Krook, Romain Barrès, Juleen R Zierath
Paternal preconceptional high-fat diet (HFD) alters whole-body glucose and energy homeostasis over several generations, which may be mediated by altered transcriptomic profiles of metabolic organs. We investigated the effect of paternal HFD on the hepatic transcriptomic and metabolic signatures of female grand-offspring. Paternal HFD strongly impacted the liver transcriptome of the second-generation offspring. Gene set enrichment analysis (GSEA) revealed grandpaternal-HFD altered the TNF-α signaling via NFκB pathway, independent of the grand-offspring's diet...
February 15, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/30768365/ipsc-and-mesenchymoangioblast-derived-mesenchymal-stem-cells-provide-greater-protection-against-experimental-chronic-allergic-airways-disease-compared-with-a-clinically-used-corticosteroid
#13
Simon G Royce, WeiYi Mao, Rebecca Lim, Kilian Kelly, Chrishan S Samuel
The airway remodeling (AWR) associated with chronic allergic airways disease (AAD)/asthma contributes to irreversible airway obstruction. This study compared and combined the antiremodeling and other effects of induced pluripotent stem cell and mesenchymoangioblast-derived mesenchymal stem cells (MCA-MSCs) with the corticosteroid dexamethasone (Dex) in experimental chronic AAD/asthma. Female BALB/c mice subjected to 11 wk of ovalbumin (Ova)-induced chronic AAD were intranasally administered MCA-MSCs (1 × 106 cells/mouse; once weekly on wk 10 and 11), Dex (0...
February 15, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/30768364/obesogenic-diet-in-aging-mice-disrupts-gut-microbe-composition-and-alters-neutrophil-lymphocyte-ratio-leading-to-inflamed-milieu-in-acute-heart-failure
#14
Vasundhara Kain, William Van Der Pol, Nithya Mariappan, Aftab Ahmad, Peter Eipers, Deanna L Gibson, Cecile Gladine, Claire Vigor, Thierry Durand, Casey Morrow, Ganesh V Halade
Calorie-dense obesogenic diet (OBD) is a prime risk factor for cardiovascular disease in aging. However, increasing age coupled with changes in the diet can affect the interaction of intestinal microbiota influencing the immune system, which can lead to chronic inflammation. How age and calorie-enriched OBD interact with microbial flora and impact leukocyte profiling is currently under investigated. Here, we tested the interorgan hypothesis to determine whether OBD in young and aging mice alters the gut microbe composition and the splenic leukocyte profile in acute heart failure (HF)...
February 15, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/30768359/taurine-alleviates-repression-of-betaine-homocysteine-s-methyltransferase-and-significantly-improves-the-efficacy-of-long-term-betaine-treatment-in-a-mouse-model-of-cystathionine-%C3%AE-synthase-deficient-homocystinuria
#15
Kenneth N Maclean, Hua Jiang, Whitney N Phinney, Amy K Keating, K Joseph Hurt, Sally P Stabler
Classical cystathionine β-synthase-deficient homocystinuria (HCU) is a life-threatening inborn error of sulfur metabolism. Treatment for pyridoxine-nonresponsive HCU involves lowering homocysteine (Hcy) with a methionine (Met)-restricted diet and betaine supplementation. Betaine treatment efficacy diminishes significantly over time due to impairment of betaine-Hcy S-methyltransferase (BHMT) function. Little is known regarding the regulation of BHMT in HCU. Using a betaine-responsive preclinical mouse model of HCU, we observed that this condition induces a 75% repression of BHMT mRNA, protein and enzyme activity, and significant depletion of hepatic betaine levels...
February 15, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/30768358/rcc2-a-regulator-of-the-rala-signaling-pathway-is-identified-as-a-novel-therapeutic-target-in-cisplatin-resistant-ovarian-cancer
#16
Shipeng Gong, Yongning Chen, Fanliang Meng, Yadi Zhang, Huan Wu, Chanyuan Li, Guangping Zhang
Currently, cisplatin (DDP) is the first-line chemotherapeutic agent used for treatment of ovarian cancer, but gradually acquired drug resistance minimizes its therapeutic outcomes. We aimed to identify crucial genes associated with DDP resistance in ovarian cancer and uncover potential mechanisms. Two sets of gene expression data were downloaded from Gene Expression Omnibus, and bioinformatics analysis was conducted. In our study, the differentially expressed genes between DDP-sensitive and DDP-resistant ovarian cancer were screened in GSE15709 and GSE51373 database, and chromosome condensation 2 regulator (RCC2) and nucleoporin 160 were identified as 2 genes that significantly up-regulated in DDP-resistant ovarian cancer cell lines compared with DDP-sensitive cell lines...
February 15, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/30763124/enhanced-osteogenic-differentiation-of-human-bone-derived-mesenchymal-stem-cells-in-3-dimensional-printed-porous-titanium-scaffolds-by-static-magnetic-field-through-up-regulating-smad4
#17
Yu He, Lingjia Yu, Jieying Liu, Yaqian Li, Yuanhao Wu, Zhenfei Huang, Di Wu, Hai Wang, Zhihong Wu, Guixing Qiu
The reconstruction of large bone defects remains a significant challenge for orthopedists. Three-dimensional-printed (3DP) scaffold is considered a promising repair material. Static magnetic field (SMF) treatment is an effective and noninvasive therapeutic method to improve bone regeneration. However, the osteogenic effect of SMF on human bone-derived mesenchymal stem cells (hBMSCs) in 3DP scaffolds, as well as its potential mechanism, are unclear. In this study, the osteogenic effect of SMF on hBMSCs in a 3DP scaffold was investigated in vitro and in vivo...
February 14, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/30759349/a-follistatin-based-molecule-increases-muscle-and-bone-mass-without-affecting-the-red-blood-cell-count-in-mice
#18
Andreas Lodberg, Bram C J van der Eerden, Bianca Boers-Sijmons, Jesper Skovhus Thomsen, Annemarie Brüel, Johannes P T M van Leeuwen, Marco Eijken
Inhibitors of the activin receptor signaling pathway (IASPs) have become candidate therapeutics for sarcopenia and bone remodeling disorders because of their ability to increase muscle and bone mass. However, IASPs utilizing activin type IIA and IIB receptors are also potent stimulators of erythropoiesis, a feature that may restrict their usage to anemic patients because of increased risk of venous thromboembolism. Based on the endogenous TGF-β superfamily antagonist follistatin (FST), a molecule in the IASP class, FSTΔHBS -mFc, was generated and tested in both ovariectomized and naive BALB/c and C57BL/6 mice...
February 13, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/30759348/functional-definition-of-nrtr-a-remnant-regulator-of-nad-homeostasis-in-the-zoonotic-pathogen-streptococcus-suis
#19
Qingjing Wang, Bachar H Hassan, Ningjie Lou, Justin Merritt, Youjun Feng
NAD+ is an enzyme cofactor required for the 3 domains of life. However, little is known about the NAD+ biosynthesis and salvage pathways in the opportunistic pathogen Streptococcus suis. A genome-wide search allows us to identify the NAD+ salvage pathway encoded by an operon of nadR-pnuC-nrtR (from SSU05_1973 to SSU05_1971 on the reverse strand) in the S. suis 05ZYH33 that causes streptococcal toxin shock-like syndrome. The regulator of this pathway is Nudix-related transcriptional regulator (NrtR), a transcription regulator of the Nudix family comprising an N-terminal Nudix-like effector domain, and a C-terminal DNA-binding winged helix-turn-helix-like domain...
February 13, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/30759346/intrauterine-exposure-to-hyperglycemia-retards-the-development-of-brown-adipose-tissue
#20
Dan-Qing Yu, Ping-Ping Lv, Yi-Shang Yan, Guan-Xin Xu, Annapurna Sadhukhan, Shan Dong, Yan Shen, Jun Ren, Xue-Ying Zhang, Chun Feng, Yi-Ting Huang, Shen Tian, Yin Zhou, Yi-Ting Cai, Zhen-Hua Ming, Guo-Lian Ding, Hong Zhu, Jian-Zhong Sheng, Min Jin, He-Feng Huang
Brown adipose tissue (BAT) is an exclusive tissue of nonshivering thermogenesis. It is fueled by lipids and glucose and involved in energy and metabolic homeostasis. Intrauterine exposure to hyperglycemia during gestational diabetes mellitus may result in abnormal fetal development and metabolic phenotypes in adulthood. However, whether intrauterine hyperglycemia influences the development of BAT is unknown. In this study, mouse embryos were exposed to the intrauterine hyperglycemia environment by injecting streptozocin into pregnant mice at 1 d post coitum (dpc)...
February 13, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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