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Juan J Nieto-Fontarigo, Francisco J González-Barcala, Esther San José, Pilar Arias, Montserrat Nogueira, Francisco J Salgado
Asthma is a heterogeneous and chronic inflammatory family of disorders of the airways with increasing prevalence that results in recurrent and reversible bronchial obstruction and expiratory airflow limitation. These diseases arise from the interaction between environmental and genetic factors, which collaborate to cause increased susceptibility and severity. Many asthma susceptibility genes are linked to the immune system or encode enzymes like metalloproteases (e.g., ADAM-33) or serine proteases. The S9 family of serine proteases (prolyl oligopeptidases) is capable to process peptide bonds adjacent to proline, a kind of cleavage-resistant peptide bonds present in many growth factors, chemokines or cytokines that are important for asthma...
August 25, 2016: Clinical Reviews in Allergy & Immunology
Yohei Shiina, Tomohiro Muto, Zhili Zhang, Ahmad Baihaqie, Takamasa Yoshizawa, Hye-In J Lee, Eulsoon Park, Shinya Tsukiji, Koichi Takimoto
Mammalian DPP6 (DPPX) and DPP10 (DPPY) belong to a family of dipeptidyl peptidases, but lack enzyme activity. Instead, these proteins form complexes with voltage-gated K(+) channels in Kv4 family to control their gating and other properties. Here, we find that the fly DPP10 ortholog acts as an ancillary subunit of Kv4 channels and digests peptides. Similarly to mammalian DPP10, the fly ortholog tightly binds to rat Kv4.3 protein. The association causes negative shifts in voltage dependence of channel activation and steady state inactivation...
2016: Scientific Reports
L Wagner, C Klemann, M Stephan, S von Hörsten
Dipeptidyl peptidase (DPP) 4 (CD26, DPP4) is a multi-functional protein involved in T cell activation by co-stimulation via its association with adenosine deaminase (ADA), caveolin-1, CARMA-1, CD45, mannose-6-phosphate/insulin growth factor-II receptor (M6P/IGFII-R) and C-X-C motif receptor 4 (CXC-R4). The proline-specific dipeptidyl peptidase also modulates the bioactivity of several chemokines. However, a number of enzymes displaying either DPP4-like activities or representing structural homologues have been discovered in the past two decades and are referred to as DPP4 activity and/or structure homologue (DASH) proteins...
June 2016: Clinical and Experimental Immunology
Chau-Fu Cheng, Wan-Chen Wang, Chia-Yi Huang, Po-Hau Du, Jung-Hui Yang, Meei-Ling Tsaur
Subthreshold A-type K(+) currents (ISA s) have been recorded from the somata of nociceptors and spinal lamina II excitatory interneurons, which sense and modulate pain, respectively. Kv4 channels are responsible for the somatodendritic ISA s. Accumulative evidence suggests that neuronal Kv4 channels are ternary complexes including pore-forming Kv4 subunits and two types of auxiliary subunits: K(+) channel-interacting proteins (KChIPs) and dipeptidyl peptidase-like proteins (DPPLs). Previous reports have shown Kv4...
March 1, 2016: Journal of Comparative Neurology
Masahiro Kitazawa, Yoshihiro Kubo, Koichi Nakajo
Kv4 is a member of the voltage-gated K(+) channel family and forms a complex with various accessory subunits. Dipeptidyl aminopeptidase-like protein (DPP) is one of the auxiliary subunits for the Kv4 channel. Although DPP has been well characterized and is known to increase the current amplitude and accelerate the inactivation and recovery from inactivation of Kv4 current, it remains to be determined how many DPPs bind to one Kv4 channel. To examine whether the expression level of DPP changes the biophysical properties of Kv4, we expressed Kv4...
September 11, 2015: Journal of Biological Chemistry
Hanga Galfalvy, Fatemeh Haghighi, Colin Hodgkinson, David Goldman, Maria A Oquendo, Ainsley Burke, Yung-Yu Huang, Ina Giegling, Dan Rujescu, Alexandre Bureau, Gustavo Turecki, J John Mann
Genome wide array studies have reported limited success in identifying genetic markers conferring risk for suicidal behavior (SB). This may be attributable to study designs with primary outcome other than SB. We performed a GWAS on suicides and cases with a history of nonfatal suicide attempts compared with psychiatric controls and healthy volunteers. A consortium of USA, Canadian and German teams assembled two groups of cases (suicide attempters and suicides, N = 577) and non-attempter psychiatric and healthy controls (N = 1,233)...
October 2015: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Michelle Cotterchio, Elizabeth Lowcock, Zoe Bider-Canfield, Mathieu Lemire, Celia Greenwood, Steven Gallinger, Thomas Hudson
BACKGROUND: Many epidemiology studies report that atopic conditions such as allergies are associated with reduced pancreas cancer risk. The reason for this relationship is not yet understood. This is the first study to comprehensively evaluate the association between variants in atopy-related candidate genes and pancreatic cancer risk. METHODS: A population-based case-control study of pancreas cancer cases diagnosed during 2011-2012 (via Ontario Cancer Registry), and controls recruited using random digit dialing utilized DNA from 179 cases and 566 controls...
2015: PloS One
Gustavo Arruda Bezerra, Elena Dobrovetsky, Alma Seitova, Sofiya Fedosyuk, Sirano Dhe-Paganon, Karl Gruber
The voltage-gated potassium channel family (Kv) constitutes the most diverse class of ion channels in the nervous system. Dipeptidyl peptidase 10 (DPP10) is an inactive peptidase that modulates the electrophysiological properties, cell-surface expression and subcellular localization of voltage-gated potassium channels. As a consequence, DPP10 malfunctioning is associated with neurodegenerative conditions like Alzheimer and fronto-temporal dementia, making this protein an attractive drug target. In this work, we report the crystal structure of DPP10 and compare it to that of DPP6 and DPP4...
2015: Scientific Reports
K Turnow, K Metzner, D Cotella, M J Morales, M Schaefer, T Christ, U Ravens, E Wettwer, S Kämmerer
The sustained component of the K(+) outward current in human atrial myocytes is believed to be due to the slowly inactivating ultra-rapid potassium current I Kur and not to the fast inactivating transient outward current Ito. Here we provide evidence for contribution of Ito to this late current due to the effects of dipeptidyl peptidase-like protein (DPP) 10 (DPP10a) interacting with Kv4.3 channels. We studied the late current component of Ito in human atrial myocytes and CHO cells co-expressing Kv4.3 or Kv4...
March 2015: Basic Research in Cardiology
Seung-Hyun Kim, Hyunna Choi, Moon-Gyung Yoon, Young-Min Ye, Hae-Sim Park
BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is an endotype of severe and eosinophilic adult asthma characterized by chronic rhinosinusitis with nasal polyps and hypersensitivity to aspirin and/or nonsteroidal anti-inflammatory drugs. A genetic contribution of dipeptidyl-peptidase 10 (DPP10) to asthma susceptibility and lung function decline has been reported. However, little is known about the role of DPP10 in the pathogenesis of AERD. OBJECTIVE: To identify genetic variants of DPP10 that confer susceptibility to AERD or severe asthma...
March 2015: Annals of Allergy, Asthma & Immunology
Divya Chhabra, Sunita Sharma, Alvin T Kho, Roger Gaedigk, Carrie A Vyhlidal, J Steven Leeder, Jarrett Morrow, Vincent J Carey, Scott T Weiss, Kelan G Tantisira, Dawn L DeMeo
In utero smoke exposure has been shown to have detrimental effects on lung function and to be associated with persistent wheezing and asthma in children. One potential mechanism of IUS effects could be alterations in DNA methylation, which may have life-long implications. The goal of this study was to examine the association between DNA methylation and nicotine exposure in fetal lung and placental tissue in early development; nicotine exposure in this analysis represents a likely surrogate for in-utero smoke...
November 2014: Epigenetics: Official Journal of the DNA Methylation Society
Wan-Chen Wang, Chau-Fu Cheng, Meei-Ling Tsaur
Subthreshold A-type K(+) currents (ISA s) have been recorded from the cell bodies of hippocampal and neocortical interneurons as well as neocortical pyramidal neurons. Kv4 channels are responsible for the somatodendritic ISA s. It has been proposed that neuronal Kv4 channels are ternary complexes including pore-forming Kv4 subunits, K(+) channel-interacting proteins (KChIPs), and dipeptidyl peptidase-like proteins (DPPLs). However, colocalization evidence was still lacking. The distribution of DPP10 mRNA in rodent brain has been reported but its protein localization remains unknown...
March 1, 2015: Journal of Comparative Neurology
Suzanne Gonzalez, Cynthia Camarillo, Marco Rodriguez, Mercedes Ramirez, Juan Zavala, Regina Armas, Salvador A Contreras, Javier Contreras, Albana Dassori, Laura Almasy, Deborah Flores, Alvaro Jerez, Henriette Raventós, Alfonso Ontiveros, Humberto Nicolini, Michael Escamilla
A genome-wide nonparametric linkage screen was performed to localize Bipolar Disorder (BP) susceptibility loci in a sample of 3757 individuals of Latino ancestry. The sample included 963 individuals with BP phenotype (704 relative pairs) from 686 families recruited from the US, Mexico, Costa Rica, and Guatemala. Non-parametric analyses were performed over a 5 cM grid with an average genetic coverage of 0.67 cM. Multipoint analyses were conducted across the genome using non-parametric Kong & Cox LOD scores along with Sall statistics for all relative pairs...
September 2014: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Tong Chen, Wei-Ping Gai, Catherine A Abbott
The neuropathological features associated with Alzheimer's disease (AD) include the presence of extracellular amyloid-β peptide-containing plaques and intracellular tau positive neurofibrillary tangles and the loss of synapses and neurons in defined regions of the brain. Dipeptidyl peptidase 10 (DPP10) is a protein that facilitates Kv4 channel surface expression and neuronal excitability. This study aims to explore DPP10789 protein distribution in human brains and its contribution to the neurofibrillary pathology of AD and other tauopathies...
2014: BioMed Research International
Mingyan Lin, Dejian Zhao, Anastasia Hrabovsky, Erika Pedrosa, Deyou Zheng, Herbert M Lachman
Schizophrenia (SZ) and autism spectrum disorders (ASD) are highly heritable neuropsychiatric disorders, although environmental factors, such as maternal immune activation (MIA), play a role as well. Cytokines mediate the effects of MIA on neurogenesis and behavior in animal models. However, MIA stimulators can also induce a febrile reaction, which could have independent effects on neurogenesis through heat shock (HS)-regulated cellular stress pathways. However, this has not been well-studied. To help understand the role of fever in MIA, we used a recently described model of human brain development in which induced pluripotent stem cells (iPSCs) differentiate into 3-dimensional neuronal aggregates that resemble a first trimester telencephalon...
2014: PloS One
Audrey H Poon, E Andres Houseman, Louise Ryan, David Sparrow, Pantel S Vokonas, Augusto A Litonjua
BACKGROUND: A substantial proportion of the general population has low lung function, and lung function is known to decrease as we age. Low lung function is a feature of several pulmonary disorders, such as uncontrolled asthma and chronic obstructive pulmonary disease. The objective of this study is to investigate the association of polymorphisms in asthma and chronic obstructive pulmonary disease candidate genes with rates of lung function decline in a general population sample of aging men...
July 2014: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Toshika Ohkawa, Yuko Fukata, Miwako Yamasaki, Taisuke Miyazaki, Norihiko Yokoi, Hiroshi Takashima, Masahiko Watanabe, Osamu Watanabe, Masaki Fukata
More than 30 mutations in LGI1, a secreted neuronal protein, have been reported with autosomal dominant lateral temporal lobe epilepsy (ADLTE). Although LGI1 haploinsufficiency is thought to cause ADLTE, the underlying molecular mechanism that results in abnormal brain excitability remains mysterious. Here, we focused on a mode of action of LGI1 autoantibodies associated with limbic encephalitis (LE), which is one of acquired epileptic disorders characterized by subacute onset of amnesia and seizures. We comprehensively screened human sera from patients with immune-mediated neurological disorders for LGI1 autoantibodies, which also uncovered novel autoantibodies against six cell surface antigens including DCC, DPP10, and ADAM23...
November 13, 2013: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Heae Surng Park, Hyun Yang Yeo, Hee Jin Chang, Kyung-Hee Kim, Ji Won Park, Byung Chang Kim, Ji Yeon Baek, Sun Young Kim, Dae Yong Kim
PURPOSE: The dipeptidyl peptidase IV (DPPIV) gene family exhibits multiple functions and is involved in the pathogenesis of various diseases. It has attracted pharmaceutical interest in the areas of metabolic disorders as well as cancer. However, clinicopathologic significance of DPPIV family in colorectal cancer is not fully understood. MATERIALS AND METHODS: The clinical relevance of DPPIV and DPP10 expression was determined by immunohistochemical staining, and by assessing its clinicopathologic correlation in 383 colorectal cancer patients with known clinical outcomes...
November 2013: Yonsei Medical Journal
Amanda C Mitchell, Rahul Bharadwaj, Catheryne Whittle, Winfried Krueger, Karoly Mirnics, Yasmin Hurd, Theodore Rasmussen, Schahram Akbarian
Less than 1.5% of the human genome encodes protein. However, vast portions of the human genome are subject to transcriptional and epigenetic regulation, and many noncoding regulatory DNA elements are thought to regulate the spatial organization of interphase chromosomes. For example, chromosomal "loopings" are pivotal for the orderly process of gene expression, by enabling distal regulatory enhancer or silencer elements to directly interact with proximal promoter and transcription start sites, potentially bypassing hundreds of kilobases of interspersed sequence on the linear genome...
June 15, 2014: Biological Psychiatry
J S Tushir, S Akbarian
A large, and still rapidly expanding literature on epigenetic regulation in the nervous system has provided fundamental insights into the dynamic regulation of DNA methylation and post-translational histone modifications in the context of neuronal plasticity in health and disease. Remarkably, however, very little is known about the potential role of chromatin-bound RNAs, including many long non-coding transcripts and various types of small RNAs. Here, we provide an overview on RNA-mediated regulation of chromatin structure and function, with focus on histone lysine methylation and psychiatric disease...
April 4, 2014: Neuroscience
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