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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/29150520/dopaminergic-neurotoxins-induce-cell-death-by-attenuating-nf-%C3%AE%C2%BAb-mediated-regulation-of-trpc1-expression-and-autophagy
#1
Pramod Sukumaran, Yuyang Sun, Neil Antonson, Brij B Singh
Alterations in Ca(2+) homeostasis affect neuronal survival. However, the identity of Ca(2+) channels and the mechanisms underlying neurotoxin-induced neuronal degeneration are not well understood. In this study, the dopaminergic neurotoxins 6-hydroxydopamine (6-OHDA) and 1-methyl -4-phenylpyridium ions (MPP(+)/MPTP), which mimic Parkinson's disease (PD), induced neuronal degeneration by decreasing store-mediated Ca(2+) entry. The function of the transient receptor potential canonical (TRPC)-1 channel was decreased upon exposure to the neurotoxins, followed by a decrease in TRPC1 expression...
November 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29146736/quantitative-high-throughput-screening-identifies-cytoprotective-molecules-that-enhance-sumo-conjugation-via-the-inhibition-of-sumo-specific-protease-senp-2
#2
Joshua D Bernstock, Daniel Ye, Jayden A Smith, Yang-Ja Lee, Florian A Gessler, Adam Yasgar, Jennifer Kouznetsova, Ajit Jadhav, Zhuoran Wang, Stefano Pluchino, Wei Zheng, Anton Simeonov, John M Hallenbeck, Wei Yang
The development of novel neuroprotective treatments for acute stroke has been fraught with failures, which supports the view of ischemic brain damage as a highly complex multifactorial process. Post-translational modifications such as small ubiquitin-like modifier (SUMO)ylation have emerged as critical molecular regulatory mechanisms in states of both homeostasis and ischemic stress, as evidenced by our previous work. Accordingly, the clinical significance of the selective control of the global SUMOylation process has become apparent in studies of ischemic pathobiology and pathophysiology...
November 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29146735/reduced-dnmt3a-increases-gdf5-expression-with-suppressed-satellite-cell-differentiation-and-impaired-skeletal-muscle-regeneration
#3
Yukino Hatazawa, Yusuke Ono, Yuma Hirose, Sayaka Kanai, Nobuharu L Fujii, Shuichi Machida, Ichizo Nishino, Takahiko Shimizu, Masaki Okano, Yasutomi Kamei, Yoshihiro Ogawa
DNA methylation is an epigenetic mechanism regulating gene expression. In this study, we observed that DNA methyltransferase 3a (Dnmt3a) expression is decreased after muscle atrophy. We made skeletal muscle-specific Dnmt3a knockout mice (Dnmt3a-KO mice). The regeneration capacity after muscle injury was markedly decreased in Dnmt3a-KO mice. Diminished mRNA and protein expression of Dnmt3a were observed in skeletal muscles as well as in satellite cells, which are important for muscle regeneration, in Dnmt3a-KO mice...
November 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29146734/humanized-mice-in-studying-efficacy-and-mechanisms-of-pd-1-targeted-cancer-immunotherapy
#4
Minan Wang, Li-Chin Yao, Mingshan Cheng, Danying Cai, Jan Martinek, Chong-Xian Pan, Wei Shi, Ai-Hong Ma, Ralph W De Vere White, Susan Airhart, Edison T Liu, Jacques Banchereau, Michael A Brehm, Dale L Greiner, Leonard D Shultz, Karolina Palucka, James G Keck
Establishment of an in vivo small animal model of human tumor and human immune system interaction would enable preclinical investigations into the mechanisms underlying cancer immunotherapy. To this end, non-obese diabetic (NOD).Cg-Prkdc(scid)IL2rg(tm1Wjl) /Sz (null; NSG) mice were transplanted with human (h)CD34(+) hematopoietic progenitor and stem cells, which leads to the development of human hematopoietic and immune systems [humanized NSG (HuNSG)]. HuNSG mice received human leukocyte antigen partially matched tumor implants from patient-derived xenografts [PDX; nonsmall cell lung cancer (NSCLC), sarcoma, bladder cancer, and triple-negative breast cancer (TNBC)] or from a TNBC cell line-derived xenograft (CDX)...
November 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29146733/effects-of-chronically-increased-vegf-a-on-the-aging-heart
#5
Alexander G Marneros
Whether approaches to chronically increase VEGF-A in the heart may have beneficial effects and prevent the development of heart failure, in part by improving cardiac perfusion, or whether this increase could have detrimental effects on cardiac performance in the aging heart, has not been tested yet. In this study, a genetic mouse model with a chronic increase in VEGF-A in the heart is shown to have increased cardiac angiogenesis and develop cardiac hypertrophy with enhanced basal cardiac performance with age progression...
November 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29146732/mir-539-5p-inhibits-experimental-choroidal-neovascularization-by-targeting-cxcr7
#6
Yifan Feng, Jing Wang, Yuanzhi Yuan, Xi Zhang, Minqian Shen, Fei Yuan
Stromal cell-derived factor-1 (SDF-1) has been previously confirmed to participate in the formation of choroidal neovascularization (CNV) via its receptor, CXC chemokine receptor (CXCR) 4; CXCR7 is a recently identified receptor for SDF-1. The molecular mechanisms and therapeutic value of CXCR7 in CNV remain undefined. In this study, experimental CNV was induced by laser photocoagulation in Brown-Norway pigmented rats, and aberrant CXCR7 overexpression was detected in the retinal pigment epithelial/choroid/sclera tissues of laser-injured eyes...
November 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29146731/organic-anion-transporting-polypeptide-1b3-as-a-dual-reporter-gene-for-fluorescence-and-magnetic-resonance-imaging
#7
Menq-Rong Wu, Hon-Man Liu, Chen-Wen Lu, Way-Hone Shen, I-Jou Lin, Li-Wen Liao, Yi-You Huang, Ming-Jium Shieh, Jong-Kai Hsiao
Reporter proteins have broad applications in visualizing molecular events at the cellular, tissue and whole-body levels. Transmembrane transporters recognizing specific molecular domains are of particular interest because they enable the migration of signal-source molecules from the extracellular space to the cytoplasm for subsequent application in multimodality imaging. Organic anion-transporting polypeptides (OATPs) have demonstrated their MRI reporter efficacy. We further expanded their use as a dual-modality reporter in MRI and noninvasive in vivo imaging system (IVIS)...
November 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29141998/vanillic-acid-attenuates-obesity-via-activation-of-the-ampk-pathway-and-thermogenic-factors-in-vivo-and-in-vitro
#8
Yunu Jung, Jinbong Park, Hye-Lin Kim, Jung-Eun Sim, Dong-Hyun Youn, JongWook Kang, Seona Lim, Mi-Young Jeong, Woong Mo Yang, Seok-Geun Lee, Kwang Seok Ahn, Jae-Young Um
Energy expenditure is a target gaining recent interest for obesity treatment. The antiobesity effect of vanillic acid (VA), a well-known flavoring agent, was investigated in vivo and in vitro High-fat diet (HFD)-induced obese mice and genetically obese db/db mice showed significantly decreased body weights after VA administration. Two major adipogenic markers, peroxisome proliferator activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), were reduced while the key factor of energy metabolism, AMPKα, was increased in the white adipose tissue and liver tissue of VA-treated mice...
November 15, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29141997/crispr-cas9-mediated-genome-editing-reveals-the-synergistic-effects-of-%C3%AE-defensin-family-members-on-sperm-maturation-in-rat-epididymis
#9
Chaobao Zhang, Yuchuan Zhou, Shengsong Xie, Qianqian Yin, Chunhua Tang, Zimei Ni, Jian Fei, Yonglian Zhang
The epididymis is a male reproductive organ involved in posttesticular sperm maturation and storage, but the mechanism underlying sperm maturation remains unclear. β-Defensins (Defbs) belong to a family of small, cysteine-rich, cationic peptides that are antimicrobial and modulate the immune response. A large number of Defb genes are expressed abundantly in the male reproductive tract, especially in the epididymis. We and other groups have shown the involvement of several Defb genes in regulation of sperm function...
November 15, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29141996/the-distinct-transcriptomes-of-slow-and-fast-adult-muscles-are-delineated-by-noncoding-rnas
#10
Vered Raz, Muhammad Riaz, Zuotian Tatum, Szymon M Kielbasa, Peter A C 't Hoen
Adult muscles have a vast adaptation capacity, enabling function switches in response to altered conditions. During intensive physical activity, disease, or aging, adult skeletal muscles change and adjust their functions. The competence to adjust varies among muscles. Muscle-specific molecular mechanisms in healthy and normal conditions could designate changes in physiologic and pathologic conditions. We generated deep mRNA-sequencing data in adult fast and slow mouse muscles, and applying paired analysis, we identified that the muscle-specific signatures are composed of half of the muscle transcriptome...
November 15, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29133342/exercise-training-protects-human-and-rodent-%C3%AE-cells-against-endoplasmic-reticulum-stress-and-apoptosis
#11
Flavia M M Paula, Nayara C Leite, Patricia C Borck, Ricardo Freitas-Dias, Miriam Cnop, Mara P T Chacon-Mikahil, Claudia R Cavaglieri, Piero Marchetti, Antonio C Boschero, Claudio C Zoppi, Decio L Eizirik
Prolonged exercise has positive metabolic effects in obese or diabetic individuals. These effects are usually ascribed to improvements in insulin sensitivity. We evaluated whether exercise also generates circulating signals that protect human and rodent β cells against endoplasmic reticulum (ER) stress and apoptosis. For this purpose, we obtained serum from humans or mice before and after an 8 wk training period. Exposure of human islets or mouse or rat β cells to human or rodent sera, respectively, obtained from trained individuals reduced cytokine (IL-1β+IFN-γ)- or chemical ER stressor-induced β-cell ER stress and apoptosis, at least in part via activation of the transcription factor STAT3...
November 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29133341/the-trafficking-protein-ehd2-positively-regulates-cardiac-sarcolemmal-katp-channel-surface-expression-role-in-cardioprotection
#12
Hua Qian Yang, Kundan Jana, Michael J Rindler, William A Coetzee
ATP-sensitive K(+) (KATP) channels uniquely link cellular energy metabolism to membrane excitability and are expressed in diverse cell types that range from the endocrine pancreas to neurons and smooth, skeletal, and cardiac muscle. A decrease in the surface expression of KATP channels has been linked to various disorders, including dysregulated insulin secretion, abnormal blood pressure, and impaired resistance to cardiac injury. In contrast, up-regulation of KATP channel surface expression may be protective, for example, by mediating the beneficial effect of ischemic preconditioning...
November 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29133340/effects-of-hawthorn-crataegus-pentagyna-leaf-extract-on-electrophysiologic-properties-of-cardiomyocytes-derived-from-human-cardiac-arrhythmia-specific-induced-pluripotent-stem-cells
#13
Sara Pahlavan, Marziyeh Shalchi Tousi, Mahdi Ayyari, Abolfazl Alirezalu, Hassan Ansari, Tomo Saric, Hossein Baharvand
Cardiac arrhythmias are major life-threatening conditions. The landmark discovery of induced pluripotent stem cells has provided a promising in vitro system for modeling hereditary cardiac arrhythmias as well as drug development and toxicity testing. Nowadays, nutraceuticals are frequently used as supplements for cardiovascular therapy. Here we studied the cardiac effects of hawthorn (Crataegus pentagyna) leaf extract using cardiomyocytes (CMs) differentiated from healthy human embryonic stem cells, long QT syndrome type 2 (LQTS2), and catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1) patient-specific induced pluripotent stem cells...
November 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29133339/decreased-ceramide-underlies-mitochondrial-dysfunction-in-charcot-marie-tooth-2f
#14
Nicholas U Schwartz, Ryan W Linzer, Jean-Philip Truman, Mikhail Gurevich, Yusuf A Hannun, Can E Senkal, Lina M Obeid
Charcot-Marie-Tooth (CMT) disease is the most commonly inherited neurologic disorder, but its molecular mechanisms remain unclear. One variant of CMT, 2F, is characterized by mutations in heat shock protein 27 (Hsp27). As bioactive sphingolipids have been implicated in neurodegenerative diseases, we sought to determine if their dysregulation is involved in CMT. Here, we show that Hsp27 knockout mice demonstrated decreases in ceramide in peripheral nerve tissue and that the disease-associated Hsp27 S135F mutant demonstrated decreases in mitochondrial ceramide...
November 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29127193/maintained-exercise-enhanced-brain-executive-function-related-to-cerebral-lactate-metabolism-in-men
#15
Takeshi Hashimoto, Hayato Tsukamoto, Saki Takenaka, Niels D Olesen, Lonnie G Petersen, Henrik Sørensen, Henning B Nielsen, Niels H Secher, Shigehiko Ogoh
High-intensity interval exercise (HIIE) improves cerebral executive function (EF), but the improvement in EF is attenuated after repeated HIIE, perhaps because of lower lactate availability for the brain. This investigation examined whether improved EF after exercise relates to brain lactate uptake. Fourteen healthy, male subjects performed 2 HIIE protocols separated by 60 min of rest. Blood samples were obtained from the right internal jugular venous bulb and from the brachial artery to determine differences across the brain for lactate (a-v difflactate), glucose (diffglucose), oxygen (diffoxygen), and brain-derived neurotrophic factor (BDNF; diffBDNF)...
November 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29127192/lipotoxic-very-long-chain-ceramides-cause-mitochondrial-dysfunction-oxidative-stress-and-cell-death-in-cardiomyocytes
#16
Brittany A Law, Xianghai Liao, Kelsey S Moore, Abigail Southard, Patrick Roddy, Ruiping Ji, Zdzislaw Sculz, Ala Bielawska, P Christian Schulze, L Ashley Cowart
Accumulating data support a role for bioactive lipids as mediators of lipotixicity in cardiomyocytes. One class of these, the ceramides, constitutes a family of molecules that differ in structure and are synthesized by distinct enzymes, ceramide synthase (CerS)1-CerS6. Data support that specific ceramides and the enzymes that catalyze their formation play distinct roles in cell function. In a mouse model of diabetic cardiomyopathy, sphingolipid profiling revealed increases in not only the CerS5-derived ceramides but also in very long chain (VLC) ceramides derived from CerS2...
November 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29127191/dysfunction-of-different-cellular-degradation-pathways-contributes-to-specific-%C3%AE-amyloid42-induced-pathologies
#17
Xuan-Ru Ji, Kuan-Chung Cheng, Yu-Ru Chen, Tzu-Yu Lin, Chun Hei Antonio Cheung, Chia-Lin Wu, Hsueh-Cheng Chiang
The endosomal-lysosomal system (ELS), autophagy, and ubiquitin-proteasome system (UPS) are cellular degradation pathways that each play a critical role in the removal of misfolded proteins and the prevention of the accumulation of abnormal proteins. Recent studies on Alzheimer's disease (AD) pathogenesis have suggested that accumulation of aggregated β-amyloid (Aβ) peptides in the AD brain results from a dysfunction in these cellular clearance systems. However, the specific roles of these pathways in the removal of Aβ peptides and the pathogenesis underlying AD are unclear...
November 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29127190/vesicle-mediated-secretion-of-misfolded-prion-protein-molecules-from-cyclosporin-a-treated-cells
#18
Ieshita Pan, Noa Roitenberg, Ehud Cohen
Loss of protein homeostasis is a hazardous situation that jeopardizes cellular functionality and viability. Cells have developed mechanisms that supervise protein integrity and direct misfolded molecules for degradation. Nevertheless, subsets of aggregation-prone proteins escape degradation and form aggregates that can underlie the development of neurodegenerative disorders. In some cases, cells deposit hazardous protein aggregates in designated sites, like aggresomes, or secrete them with vesicles. The prion protein (PrP) is an aggregation-prone, membrane-anchored glycoprotein, whose aggregation causes familial and sporadic, fatal, neurodegenerative diseases...
November 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29127189/autophagy-promotes-escape-from-phosphatidylinositol-3-kinase-inhibition-in-estrogen-receptor-positive-breast-cancer
#19
Wei Yang, Sarah R Hosford, Nicole A Traphagen, Kevin Shee, Eugene Demidenko, Stephanie Liu, Todd W Miller
Hyperactivation of the PI3K pathway has been implicated in resistance to antiestrogen therapies in estrogen receptor α (ER)-positive breast cancer, prompting the development of therapeutic strategies to inhibit this pathway. Autophagy has tumor-promoting and -suppressing roles and has been broadly implicated in resistance to anticancer therapies, including antiestrogens. Chloroquine (CQ) is an antimalarial and amebicidal drug that inhibits autophagy in mammalian cells and human tumors. Herein, we observed that CQ inhibited proliferation and autophagy in ER(+) breast cancer cells...
November 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29127188/epigenetically-mediated-inhibition-of-s-adenosylhomocysteine-hydrolase-and-the-associated-dysregulation-of-1-carbon-metabolism-in-nonalcoholic-steatohepatitis-and-hepatocellular-carcinoma
#20
Igor P Pogribny, Kostiantyn Dreval, Iryna Kindrat, Stepan Melnyk, Leandro Jimenez, Aline de Conti, Volodymyr Tryndyak, Marta Pogribna, Juliana Festa Ortega, S Jill James, Ivan Rusyn, Frederick A Beland
The substantial rise in the prevalence of nonalcoholic steatohepatitis (NASH), an advanced form of nonalcoholic fatty liver disease, and the strong association between NASH and the development of hepatocellular carcinoma indicate the urgent need for a better understanding of the underlying mechanisms. In the present study, by using the Stelic animal model of NASH and NASH-derived liver carcinogenesis, we investigated the role of the folate-dependent 1-carbon metabolism in the pathogenesis of NASH. We demonstrated that advanced NASH and NASH-related liver carcinogenesis are characterized by a significant dysregulation of 1-carbon homeostasis, with diminished expression of key 1-carbon metabolism genes, especially a marked inhibition of the S-adenosylhomocysteine hydrolase (Ahcy) gene and an increased level of S-adenosyl-l-homocysteine (SAH)...
November 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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