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https://www.readbyqxmd.com/read/28799229/sitagliptin-mediated-preservation-of-endothelial-progenitor-cell-function-via-augmenting-autophagy-enhances-ischaemic-angiogenesis-in-diabetes
#1
Xiaozhen Dai, Jun Zeng, Xiaoqing Yan, Qian Lin, Kai Wang, Jing Chen, Feixia Shen, Xuemei Gu, Yuehui Wang, Jun Chen, Kejian Pan, Lu Cai, Kupper A Wintergerst, Yi Tan
Recently, the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin, a major anti-hyperglycaemic agent, has received substantial attention as a therapeutic target for cardiovascular diseases via enhancing the number of circulating endothelial progenitor cells (EPCs). However, the direct effects of sitagliptin on EPC function remain elusive. In this study, we evaluated the proangiogenic effects of sitagliptin on a diabetic hind limb ischaemia (HLI) model in vivo and on EPC culture in vitro. Treatment of db/db mice with sitagliptin (Januvia) after HLI surgery efficiently enhanced ischaemic angiogenesis and blood perfusion, which was accompanied by significant increases in circulating EPC numbers...
August 10, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28790917/effect-of-dipeptidyl-peptidase-4-inhibitors-on-bone-metabolism-and-the-possible-underlying-mechanisms
#2
REVIEW
Yinqiu Yang, Chenhe Zhao, Jing Liang, Mingxiang Yu, Xinhua Qu
Diabetes mellitus has been demonstrated to be closely associated with osteoporosis. Accordingly, hypoglycemic therapy is considered effective in treating metabolic bone disease. Recently, the effects of dipeptidyl peptidase-4 (DPP-4) inhibitors, a new type of antidiabetic drug, on bone metabolism have been widely studied. This review mainly describes the effects of DPP-4 inhibitors on bone metabolism, including their effects on bone mineral density, bone quality, and fracture risk. In addition, the potential underlying mechanisms are discussed...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28771933/impact-of-clinical-evidence-communications-and-drug-regulation-changes-concerning-rosiglitazone-on-prescribing-patterns-of-antidiabetic-therapies
#3
Yoojin Noh, Dae Ryong Kang, Dae Jung Kim, Kwang Jae Lee, Sukhyang Lee, Sooyoung Shin
PURPOSE: Cardiovascular safety alerts about rosiglitazone resulted in regulatory actions in several countries in 2010, but the Food and Drug Administration eliminated access restrictions in 2013, reflecting new evidence concerning the drug safety. We investigated the effects of safety signals and regulation shifts concerning rosiglitazone on prescribing of antidiabetic drugs (ADs). METHODS: Patient data were extracted from the Korean health insurance claims database for 2007 to 2015...
August 3, 2017: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/28771625/inhibition-of-dipeptidyl-peptidase-4-ameliorates-cardiac-ischemia-and-systolic-dysfunction-by-up-regulating-the-fgf-2-egr-1-pathway
#4
Masayoshi Suda, Ippei Shimizu, Yohko Yoshida, Yuka Hayashi, Ryutaro Ikegami, Goro Katsuumi, Takayuki Wakasugi, Yutaka Yoshida, Shujiro Okuda, Tomoyoshi Soga, Tohru Minamino
Dipeptidyl peptidase 4 inhibitors are used worldwide in the management of diabetes, but their role in the prevention or treatment of cardiovascular disorders has yet to be defined. We found that linagliptin, a DPP-4 inhibitor, suppressed capillary rarefaction in the hearts of mice with dietary obesity. Metabolomic analysis performed with capillary electrophoresis/mass spectrometry (LC-MS/MS) showed that linagliptin promoted favorable metabolic remodeling in cardiac tissue, which was characterized by high levels of citrulline and creatine...
2017: PloS One
https://www.readbyqxmd.com/read/28765224/genome-wide-sensitivity-analysis-of-the-microsymbiont-sinorhizobium-meliloti-to-symbiotically-important-defensin-like-host-peptides
#5
Markus F F Arnold, Mohammed Shabab, Jon Penterman, Kevin L Boehme, Joel S Griffitts, Graham C Walker
The model legume species Medicago truncatula expresses more than 700 nodule-specific cysteine-rich (NCR) signaling peptides that mediate the differentiation of Sinorhizobium meliloti bacteria into nitrogen-fixing bacteroids. NCR peptides are essential for a successful symbiosis in legume plants of the inverted-repeat-lacking clade (IRLC) and show similarity to mammalian defensins. In addition to signaling functions, many NCR peptides exhibit antimicrobial activity in vitro and in vivo Bacterial resistance to these antimicrobial activities is likely to be important for symbiosis...
August 1, 2017: MBio
https://www.readbyqxmd.com/read/28743213/kallikrein-related-peptidase-4-contributes-to-the-tumor-metastasis-of-oral-squamous-cell-carcinoma
#6
Zhi Cui, Ye Cui, Gan Luo, Shuting Yang, Xinlian Ling, Yixin Lou, Xinhua Sun
Oral squamous cell carcinoma (OSCC) is a disfiguring malignancy and significantly impacts the quality of patient's life. Kallikrein-related peptidase 4 (KLK4), which is closely related to cancers, is highly expressed in OSCC. To explore the biological function of KLK4 in OSCC, a KLK4-specific shRNA was used to silence its endogenous expression, and then the migration and invasion of OSCC cells were explored. Results of our study showed that silencing KLK4 inhibited the migration and invasion of OSCC cells. The protein levels of epithelial mesenchymal transition-associated markers and proteases were also altered by KLK4 silencing...
September 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28731783/identification-of-sppl2a-inhibitors-by-multiparametric-analysis-of-a-high-content-ultra-high-throughput-screen
#7
Xian Zhang, Marjo Götte, Yvonne Ibig-Rehm, Ansgar Schuffenhauer, Marion Kamke, Dan Beisner, Danilo Guerini, Daniela Siebert, Ghislain M C Bonamy, Daniela Gabriel, Ursula Bodendorf
The intramembrane protease signal peptide peptidase-like 2a (SPPL2a) is a potential drug target for the treatment of autoimmune diseases due to an essential role in B cells and dendritic cells. To screen a library of 1.4 million compounds for inhibitors of SPPL2a, we developed an imaging assay detecting nuclear translocation of the proteolytically released cytosolic substrate fragment. The state-of-the-art hit calling approach based on nuclear translocation resulted in numerous false-positive hits, mainly interrupting intracellular protein trafficking...
July 1, 2017: SLAS Discovery
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
#8
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
#9
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
#10
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
#11
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/28703769/glycosaminoglycans-regulate-cxcr3-ligands-at-distinct-levels-protection-against-processing-by-dipeptidyl-peptidase-iv-cd26-and-interference-with-receptor-signaling
#12
Mieke Metzemaekers, Anneleen Mortier, Rik Janssens, Daiane Boff, Lotte Vanbrabant, Nicole Lamoen, Jo Van Damme, Mauro M Teixeira, Ingrid De Meester, Flávio A Amaral, Paul Proost
CXC chemokine ligand (CXCL)9, CXCL10 and CXCL11 direct chemotaxis of mainly T cells and NK cells through activation of their common CXC chemokine receptor (CXCR)3. They are inactivated upon NH₂-terminal cleavage by dipeptidyl peptidase IV/CD26. In the present study, we found that different glycosaminoglycans (GAGs) protect the CXCR3 ligands against proteolytic processing by CD26 without directly affecting the enzymatic activity of CD26. In addition, GAGs were shown to interfere with chemokine-induced CXCR3 signaling...
July 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28698362/structural-insights-into-lipoprotein-n-acylation-by-escherichia-coli-apolipoprotein-n-acyltransferase
#13
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 25, 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
#14
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
#15
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
#16
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
#17
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
#18
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 an 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...
August 1, 2017: Biochemistry
https://www.readbyqxmd.com/read/28642545/high-throughput-screening-of-small-molecule-inhibitors-of-the-streptococcus-quorum-sensing-signal-pathway
#19
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
#20
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
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