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https://www.readbyqxmd.com/read/28717930/understanding-the-phenotypic-similarities-between-ifap-and-olmsted-syndrome-from-a-molecular-perspective-the-interaction-of-mbtps2-and-trpv3
#1
Georges Nemer, Rémi Safi, Firas Kreidieh, Julnar Usta, Christina Bergqvist, Farah Ballout, Waed Btadini, Nour Hamzeh, Ossama Abbas, Abdul Ghani Kibbi, Yutaka Shimomura, Mazen Kurban
Ichthyosis Follicularis, Atrichia, and Photophobia (IFAP) is a severe rare genetic disorder caused by mutations in the gene encoding the Membrane-Bound Transcription Factor Peptidase, Site 2 (MBTPS2). Olmsted syndrome is another rare genetic disease with overlapping clinical features caused by mutations in the gene encoding the Transient Receptor Potential Cation Channel, subfamily V (TRPV3). Mutations in MBTPS2 have been recently reported in Olmsted syndrome, underscoring the overlap and the confusion in separating Olmsted from IFAP syndrome...
July 17, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28715446/active-subfractions-of-abelmoschus-esculentus-substantially-prevent-free-fatty-acid-induced-%C3%AE-cell-apoptosis-via-inhibiting-dipeptidyl-peptidase-4
#2
Chien-Ning Huang, Chau-Jong Wang, Yi-Ju Lee, Chiung-Huei Peng
Lipotoxicity plays an important role in exacerbating type 2 diabetes mellitus (T2DM) and leads to apoptosis of β cells. Recently dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as a useful tool in the treatment of T2DM. DPP-4 degrades type 1 glucagon-like peptide (GLP-1), and GLP-1 receptor (GLP-1R) signaling has been shown to protect β cells by modulating AMPK/mTOR, PI3K, and Bax. The anti-hyperglycemic effect of Abelmoschus esculentus (AE) is well known, however its mucilage makes it difficult to further examine this effect...
2017: PloS One
https://www.readbyqxmd.com/read/28713268/sitagliptin-an-anti-diabetic-drug-suppresses-estrogen-deficiency-induced-osteoporosisin-vivo-and-inhibits-rankl-induced-osteoclast-formation-and-bone-resorption-in-vitro
#3
Chuandong Wang, Fei Xiao, Xinhua Qu, Zanjing Zhai, Guoli Hu, Xiaodong Chen, Xiaoling Zhang
Postmenopausal osteoporosis is a disease characterized by excessive osteoclastic bone resorption. Some anti-diabetic drugs were demonstrated for anti-osteoclastic bone-loss effects. The present study investigated the skeletal effects of chronic administration of sitagliptin, a dipeptidyl peptidase IV (DPP IV) inhibitor that is increasingly used for type 2 diabetes treatments, in an estrogen deficiency-induced osteoporosis and elucidated the associated mechanisms. This study indicated that sitagliptin effectively prevented ovariectomy-induced bone loss and reduced osteoclast numbers in vivo...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28710180/dipeptidyl-peptidase-4-regulates-hematopoietic-stem-cell-activation-in-response-to-chronic-stress
#4
Enbo Zhu, Lina Hu, Hongxian Wu, Limei Piao, Guangxian Zhao, Aiko Inoue, Weon Kim, Chenglin Yu, Wenhu Xu, Yasuko K Bando, Xiang Li, Yanna Lei, Chang-Ning Hao, Kyosuke Takeshita, Woo-Shik Kim, Kenji Okumura, Toyoaki Murohara, Masafumi Kuzuya, Xian Wu Cheng
BACKGROUND: DPP4 (Dipeptidyl peptidase-4)-GLP-1 (glucagon-like peptide-1) and its receptor (GLP-1R) axis has been involved in several intracellular signaling pathways. The Adrβ3 (β3-adrenergic receptor)/CXCL12 (C-X-C motif chemokine 12) signal was required for the hematopoiesis. We investigated the novel molecular requirements between DPP4-GLP-1/GLP-1 and Adrβ3/CXCL12 signals in bone marrow (BM) hematopoietic stem cell (HSC) activation in response to chronic stress. METHODS AND RESULTS: Male 8-week-old mice were subjected to 4-week intermittent restrain stress and orally treated with vehicle or the DPP4 inhibitor anagliptin (30 mg/kg per day)...
July 14, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28698362/structural-insights-into-lipoprotein-n-acylation-by-escherichia-coli-apolipoprotein-n-acyltransferase
#5
Cameron L Noland, Michele D Kattke, Jingyu Diao, Susan L Gloor, Homer Pantua, Mike Reichelt, Anand K Katakam, Donghong Yan, Jing Kang, Inna Zilberleyb, Min Xu, Sharookh B Kapadia, Jeremy M Murray
Gram-negative bacteria express a diverse array of lipoproteins that are essential for various aspects of cell growth and virulence, including nutrient uptake, signal transduction, adhesion, conjugation, sporulation, and outer membrane protein folding. Lipoprotein maturation requires the sequential activity of three enzymes that are embedded in the cytoplasmic membrane. First, phosphatidylglycerol:prolipoprotein diacylglyceryl transferase (Lgt) recognizes a conserved lipobox motif within the prolipoprotein signal sequence and catalyzes the addition of diacylglycerol to an invariant cysteine...
July 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28687334/a-cysteine-protease-cathepsin-z-from-disk-abalone-haliotis-discus-discus-genomic-characterization-and-transcriptional-profiling-during-bacterial-infections
#6
G I Godahewa, N C N Perera, Sukkyoung Lee, Myoung-Jin Kim, Jehee Lee
Cathepsin Z (CTSZ) is lysosomal cysteine protease of the papain superfamily. It participates in the host immune defense via phagocytosis, signal transduction, cell-cell communication, proliferation, and migration of immune cells such as monocytes, macrophages, and dendritic cells. Hence, CTSZ is also acknowledged as an acute-phase protein in host immunity. In this study, we sought to identify the CTSZ homolog from disk abalone (AbCTSZ) and characterize it at the molecular, genomic, and transcriptional levels...
July 4, 2017: Gene
https://www.readbyqxmd.com/read/28686724/dipeptidyl-peptidase-4-inhibitor-gemigliptin-protects-against-vascular-calcification-in-an-experimental-chronic-kidney-disease-and-vascular-smooth-muscle-cells
#7
Soon-Youn Choi, Hye-Myung Ryu, Eun-Joo Oh, Ji-Young Choi, Jang-Hee Cho, Chan-Duck Kim, Yong-Lim Kim, Sun-Hee Park
Although dipeptidyl peptidase-4 inhibitors, a class of antidiabetic drugs, have various pleiotropic effects, it remains undetermined whether gemigliptin has a beneficial effect on vascular calcification. Therefore, this study was performed to evaluate the effect of gemigliptin on vascular calcification in a rat model of adenine-induced chronic kidney disease and in cultured vascular smooth muscle cells. Gemigliptin attenuated calcification of abdominal aorta and expression of RUNX2 in adenine-induced chronic kidney disease rats...
2017: PloS One
https://www.readbyqxmd.com/read/28684768/cloning-and-characterization-of-the-first-serine-carboxypeptidase-from-a-plant-parasitic-nematode-radopholus-similis
#8
Xin Huang, Chun-Ling Xu, Wan-Zhu Chen, Chun Chen, Hui Xie
Radopholus similis is an important parasitic nematode of plants. Serine carboxypeptidases (SCPs) are peptidases that hydrolyse peptides and proteins and play critical roles in the development, invasion, and pathogenesis of certain parasitic nematodes and other animal pathogens. In this study, we obtained the full-length sequence of the SCP gene from R. similis (Rs-scp-1), which is 1665 bp long and includes a 1461-bp open reading frames encoding 486 amino acids with an 18-aa signal peptide. This gene is a double-copy gene in R...
July 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28684129/chemokine-isoforms-and-processing-in-inflammation-and-immunity
#9
REVIEW
Paul Proost, Sofie Struyf, Jo Van Damme, Pierre Fiten, Estefania Ugarte-Berzal, Ghislain Opdenakker
The first dimension of chemokine heterogeneity is reflected by their discovery and purification as natural proteins. Each of those chemokines attracted a specific inflammatory leukocyte type. With the introduction of genomic technologies, a second wave of chemokine heterogeneity was established by the discovery of putative chemokine-like sequences and by demonstrating chemotactic activity of the gene products in physiological leukocyte homing. In the postgenomic era, the third dimension of chemokine heterogeneity is the description of posttranslational modifications on most chemokines...
July 3, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28675292/substrate-specificity-of-the-secreted-nisin-leader-peptidase-nisp
#10
Marcel Lagedroste, Sander H J Smits, Lutz Schmitt
Nisin (NisA) is an antimicrobial peptide produced by Lactococcus lactis and belongs to the class of lanthipeptides, more specifically to the class of lantibiotics. They are ribosomally synthesized as a precursor peptide and are comprised of a N-terminal leader peptide and a C-terminal core peptide. The core peptide is post-translationally modified and contains dehydrated amino acids in addition to five (methyl)-lanthionine rings, which are crucial for its activity. The leader peptide serves as a signal sequence and ensures that NisA remains inactive but secretion-competent within the cell...
July 4, 2017: Biochemistry
https://www.readbyqxmd.com/read/28642545/high-throughput-screening-of-small-molecule-inhibitors-of-the-streptococcus-quorum-sensing-signal-pathway
#11
Seiji Ishii, Kenji Fukui, Satoshi Yokoshima, Kazuo Kumagai, Youko Beniyama, Tetsuya Kodama, Tohru Fukuyama, Takayoshi Okabe, Tetsuo Nagano, Hirotatsu Kojima, Takato Yano
The main components of the quorum-sensing system are expected to be favorable targets for drug development to combat various chronic infectious diseases. ComA of Streptococcus is an ATP-binding cassette transporter containing a peptidase domain (PEP), which is essential for the quorum-sensing signal production. Using high-throughput screening, we found a potent small molecule that suppressed the S. mutans quorum-sensing pathway through inhibition of PEP activity. The compound effectively attenuated the biofilm formation and competence development of S...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630282/desumoylation-of-gli1-by-senp1-attenuates-sonic-hedgehog-signaling
#12
Huaize Liu, Sen Yan, Jie Ding, Ting-Ting Yu, Steven Y Cheng
Transcriptional output of the Sonic hedgehog morphogenic pathway is orchestrated by three Krüppel family transcription factors, Gli1-3, which undergo extensive post-translational modifications, including ubiquitination and SUMOylation. Here, we report that sentrin-specific peptidase SENP1 is the specific de-SUMOylation enzyme for Gli1. We show that SUMOylation stabilizes Gli1 by competing with ubiquitination at conserved lysine residues, and SUMOylated Gli1 is enriched in the nucleus, suggesting that SUMOylation is a nuclear localization signal for Gli1...
June 19, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28630262/dipeptidyl-peptidase-4-inhibitor-anagliptin-prevents-intracranial-aneurysm-growth-by-suppressing-macrophage-infiltration-and-activation
#13
Taichi Ikedo, Manabu Minami, Hiroharu Kataoka, Kosuke Hayashi, Manabu Nagata, Risako Fujikawa, Sei Higuchi, Mika Yasui, Tomohiro Aoki, Miyuki Fukuda, Masayuki Yokode, Susumu Miyamoto
BACKGROUND: Chronic inflammation plays a key role in the pathogenesis of intracranial aneurysms (IAs). DPP-4 (dipeptidyl peptidase-4) inhibitors have anti-inflammatory effects, including suppressing macrophage infiltration, in various inflammatory models. We examined whether a DPP-4 inhibitor, anagliptin, could suppress the growth of IAs in a rodent aneurysm model. METHODS AND RESULTS: IAs were surgically induced in 7-week-old male Sprague Dawley rats, followed by oral administration of 300 mg/kg anagliptin...
June 19, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28624439/signal-peptide-peptidase-and-spp-like-proteases-possible-therapeutic-targets
#14
REVIEW
Torben Mentrup, Ann-Christine Loock, Regina Fluhrer, Bernd Schröder
Signal peptide peptidase (SPP) and the four homologous SPP-like proteases SPPL2a, SPPL2b, SPPL2c and SPPL3 are GxGD-type intramembrane-cleaving proteases (I-CLIPs). In addition to divergent subcellular localisations, distinct differences in the mechanistic properties and substrate requirements of individual family members have been unravelled. SPP/SPPL proteases employ a catalytic mechanism related to that of the γ-secretase complex. Nevertheless, differential targeting of SPP/SPPL proteases and γ-secretase by inhibitors has been demonstrated...
June 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28620125/mutational-re-modeling-of-di-aspartyl-intramembrane-proteases-uncoupling-physiologically-relevant-activities-from-those-associated-with-alzheimer-s-disease
#15
Anastasia P Grigorenko, Youri K Moliaka, Olga V Plotnikova, Alexander Smirnov, Vera A Nikishina, Andrey Y Goltsov, Fedor Gusev, Tatiana V Andreeva, Omar Nelson, Ilya Bezprozvanny, Evgeny I Rogaev
The intramembrane proteolytic activities of presenilins (PSEN1/PS1 and PSEN2/PS2) underlie production of β-amyloid, the key process in Alzheimer's disease (AD). Dysregulation of presenilin-mediated signaling is linked to cancers. Inhibition of the γ-cleavage activities of PSENs that produce Aβ, but not the ε-like cleavage activity that release physiologically essential transcription activators, is a potential approach for the development of rational therapies for AD. In order to identify whether different activities of PSEN1 can be dissociated, we designed multiple mutations in the evolutionary conserved sites of PSEN1...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28608197/cysteine-protease-zymography-brief-review
#16
Jeff Wilkesman
Cysteine proteases play multiple roles in basically all aspects of physiology and development. In plants, they are involved in growth and development and in accumulation and mobilization of storage proteins. Furthermore, they are engaged in signalling pathways and in the response to biotic and abiotic stresses. In animals and also in humans, they are responsible for senescence and apoptosis, prohormone processing, and ECM remodelling. When analyzed by zymography, the enzyme must be renaturated after SDS-PAGE...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28589493/a-randomized-placebo-controlled-trial-evaluating-the-safety-and-efficacy-of-adding-omarigliptin-to-antihyperglycemic-therapies-in-japanese-patients-with-type-2-diabetes-and-inadequate-glycemic-control
#17
Ira Gantz, Taro Okamoto, Yuka Ito, Asako Sato, Kotoba Okuyama, Edward A O'Neill, Samuel S Engel, Eseng Lai
INTRODUCTION: Daily dipeptidyl peptidase-4 (DPP-4) inhibitors are commonly used with other orally administered antihyperglycemic agents (AHA), as combination therapy, to treat Japanese patients with type 2 diabetes. When combination therapy is indicated, use of a once-weekly (q.w.) orally administered DPP-4 inhibitor might be an appropriate therapeutic option for some patients. METHODS: A 52-week trial was conducted to assess the safety and tolerability (primary objectives) and glycemic efficacy (secondary objectives) of the q...
June 6, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28576404/attenuated-diuresis-and-natriuresis-in-response-to-glucagon-like-peptide-1-in-hypertensive-rats-are-associated-with-lower-expression-of-the-glucagon-like-peptide-1-receptor-in-the-renal-vasculature
#18
Fernanda A Savignano, Renato O Crajoinas, Bruna P M Pacheco, Luciene C G Campos, Maria Heloisa M Shimizu, Antonio Carlos Seguro, Adriana C C Girardi
Accumulating evidence from clinical and experimental studies indicates that the incretin glucagon-like peptide-1 (GLP-1) elicits blood-pressure lowering effects via its diuretic, natriuretic and vasodilatory properties. The present study investigated whether acute infusion of GLP-1 induces diuresis and natriuresis in spontaneously hypertensive rats (SHRs). Additionally, we examined whether GLP-1 influences the vascular reactivity of the renal arteries of normotensive and hypertensive rats and elucidated the underlying mechanisms...
May 30, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28575350/dipeptidyl-peptidase-iv-as-a-prognostic-marker-and-therapeutic-target-in-papillary-thyroid-carcinoma
#19
Jie-Jen Lee, Tao-Yeuan Wang, Chien-Liang Liu, Ming-Nan Chien, Ming-Jen Chen, Yi-Chiung Hsu, Ching-Hsiang Leung, Shih-Ping Cheng
Context: Dipeptidyl peptidase IV (DPP4) is overexpressed in thyroid cancer and certain malignancies. Furthermore, DPP4 has been identified as a discriminatory marker for thyroid cancer. However, it remains unclear whether DPP4 expression plays a prognostic role. Objective: The aim of this study was to investigate the expression and function of DPP4 in thyroid cancer and the mechanisms involved. Design: We determined the expression of DPP4 by immunohistochemistry in tissue microarrays of thyroid tumors...
May 26, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28559295/polyvalent-proteins-a-pervasive-theme-in-the-inter-genomic-biological-conflicts-of-bacteriophages-and-conjugative-elements
#20
Lakshminarayan M Iyer, A Maxwell Burroughs, Swadha Anand, Robson F de Souza, L Aravind
Intense biological conflicts between prokaryotic genomes and their genomic parasites have resulted in an arms-race in terms of the molecular "weaponry" deployed on both sides. Using a recursive computational approach we uncovered a remarkable class of multidomain proteins with 2-15 domains in the same polypeptide deployed by viruses and plasmids in such conflicts. Domain architectures and genomic contexts indicate that they are part of a widespread conflict strategy involving proteins injected into the host cell along with parasite DNA during the earliest phase of infection...
May 30, 2017: Journal of Bacteriology
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