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Calcineurin

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https://www.readbyqxmd.com/read/27911714/regulation-of-the-phosphatase-pp2b-by-protein-protein-interactions
#1
REVIEW
Patrick J Nygren, John D Scott
Protein dephosphorylation is important for regulating cellular signaling in a variety of contexts. Protein phosphatase-2B (PP2B), or calcineurin, is a widely expressed serine/threonine phosphatase that acts on a large cross section of potential protein substrates when activated by increased levels of intracellular calcium in concert with calmodulin. PxIxIT and LxVP targeting motifs are important for maintaining specificity in response to elevated calcium. In the present study, we describe the mechanism of PP2B activation, discuss its targeting by conserved binding motifs and review recent advances in the understanding of an A-kinase anchoring protein 79/PP2B/protein kinase A complex's role in synaptic long-term depression...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27910751/recent-advances-in-pharmacotherapeutic-paradigm-of-mild-to-recalcitrant-atopic-dermatitis
#2
Zahid Hussain, Shariza Sahudin, Hnin Ei Thu, Ahmad Nazrun Shuid, Syed Nasir Abbas Bukhari, Endang Kumolosasi
Atopic dermatitis (AD) is a common, chronic skin inflammatory disorder characterized by perivascular infiltration of immunoglobulin E (IgE), T lymphocytes, and mast cells. The key factors responsible for the pathophysiology of this disease are immunological disorders and defects in epidermal barrier properties. Pruritus, intense itching, psychological stress, deprived physical and mental performance, and sleep disturbance are the hallmark features of this dermatological disorder. Preventive interventions such as educational programs, avoidance of allergens, and exclusive care toward the skin could play a partial role in suppressing the symptoms...
2016: Critical Reviews in Therapeutic Drug Carrier Systems
https://www.readbyqxmd.com/read/27909728/calcineurin-nuclear-factor-%C3%AE%C2%BAb-signaling-mediates-isoflurane-induced-hippocampal-neuroinflammation-and-subsequent-cognitive-impairment-in-aged-rats
#3
Zhengqian Li, Cheng Ni, Chun Xia, Joey Jaw, Yujie Wang, Yiyun Cao, Mao Xu, Xiangyang Guo
It is known that inhaled anesthetics induce neuroinflammation and facilitate postoperative cognitive dysfunction (POCD) in aged individuals; however, the mechanisms by which they mediate these effects remain elusive. Inhalation of the isoflurane anesthetic leads to opening of the mitochondrial permeability transition pore and loss of mitochondrial membrane potential. Therefore, mitochondrial retrograde signaling, which is an adaptive mechanism that facilitates the transmission of signals from dysfunctional mitochondria to the nucleus to activate target gene expression, may be activated during isoflurane inhalation...
November 24, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27904832/frontal-fibrosing-alopecia-treatment-options
#4
Raymond Fertig, Antonella Tosti
Frontal fibrosing alopecia (FFA) is a rare dermatologic disease that causes scarring and hair loss and is increasing in prevalence worldwide. FFA patients typically present with hair loss in the frontal scalp region and eyebrows which may be associated with sensations of itching or burning. FFA is a clinically distinct variant of lichen planopilaris (LPP) that affects predominantly postmenopausal women, although men and premenopausal women may also be affected. Early diagnosis and prompt treatment are necessary to prevent definitive scarring and permanent hair loss...
November 2016: Intractable & Rare Diseases Research
https://www.readbyqxmd.com/read/27904185/topical-therapy-in-atopic-dermatitis-in-children
#5
Dharshini Sathishkumar, Celia Moss
Atopic dermatitis (AD) is a common, chronic childhood skin disorder caused by complex genetic, immunological, and environmental interactions. It significantly impairs quality of life for both child and family. Treatment is complex and must be tailored to the individual taking into account personal, social, and emotional factors, as well as disease severity. This review covers the management of AD in children with topical treatments, focusing on: education and empowerment of patients and caregivers, avoidance of trigger factors, repair and maintenance of the skin barrier by correct use of emollients, control of inflammation with topical corticosteroids and calcineurin inhibitors, minimizing infection, and the use of bandages and body suits...
November 2016: Indian Journal of Dermatology
https://www.readbyqxmd.com/read/27903993/effects-of-angiotensin-ii-receptor-blockade-on-soluble-klotho-and-oxidative-stress-in-calcineurin-inhibitor-nephrotoxicity-in-rats
#6
Sina Raeisi, Amir Ghorbanihaghjo, Hassan Argani, Siavoush Dastmalchi, Babollah Ghasemi, Teimour Ghazizadeh, Nadereh Rashtchizadeh, Mahboob Nemati, Mehran Mesgari Abbasi, Nasrin Bargahi, Ali Mota, Amir Mansour Vatankhah
INTRODUCTION: Calcineurin inhibitor nephrotoxicity is major problem after organ transplantation. It is multifactorial, but oxidative stress may have an important role in this process. It has been shown that angiotensin II receptor blockers have renoprotective effects but their molecular mechanism is largely unknown. Antioxidative effect is an important role of the recently known anti-aging protein, klotho. This study aimed to evaluate effect of valsartan in alleviation of cyclosporine A nephrotoxicity via a probable increase in serum klotho levels or decreasing oxidative stress...
November 2016: Iranian Journal of Kidney Diseases
https://www.readbyqxmd.com/read/27902816/association-of-filaggrin-loss-of-function-and-thymic-stromal-lymphopoietin-variation-with-treatment-use-in-pediatric-atopic-dermatitis
#7
Joshua Chang, Nandita Mitra, Ole Hoffstad, David J Margolis
Importance: Atopic dermatitis (AD) is a common illness of childhood. Objective: To determine whether variations in FLG and TSLP genotype corresponded to differences in treatment use over time. Design, Setting, and Participants: This prospective cohort study recruited and followed a volunteer sample of 842 children enrolled in the Pediatric Eczema Elective Registry who provided saliva samples for DNA extraction for 10 years. Eligibility criteria included age 2 to 17 years, AD diagnosis without cancer, and prior pimecrolimus use...
November 30, 2016: JAMA Dermatology
https://www.readbyqxmd.com/read/27899535/a-tomato-universal-stress-protein-involved-in-oxidative-stress-is-a-cipk6-phosphorylation-target
#8
Emilio Gutierrez-Beltran, José María Personat, Fernando N de la Torre, Olga Del Pozo
Calcineurin B-like interacting protein kinases (CIPKs) decode calcium signals upon interaction with the calcium sensors calcineurin B like proteins (CBLs) into phosphorylation events that result into adaptation to environmental stresses. Few phosphorylation targets of CIPKs are known and therefore the molecular mechanisms underlying their downstream output responses are not fully understood. Tomato (Solanum lycopersicum) Cipk6 regulates immune and susceptible Programmed cell death (PCD) in immunity transforming Ca2+ signals into Reactive Oxygen Species (ROS) signaling...
November 29, 2016: Plant Physiology
https://www.readbyqxmd.com/read/27899413/calcium-channel-regulator-mid1-links-torc2-mediated-changes-in-mitochondrial-respiration-to-autophagy
#9
Ariadne Vlahakis, Nerea Lopez Muniozguren, Ted Powers
Autophagy is a catabolic process that recycles cytoplasmic contents and is crucial for cell survival during stress. The target of rapamycin (TOR) kinase regulates autophagy as part of two distinct protein complexes, TORC1 and TORC2. TORC1 negatively regulates autophagy according to nitrogen availability. In contrast, TORC2 functions as a positive regulator of autophagy during amino acid starvation, via its target kinase Ypk1, by repressing the activity of the calcium-dependent phosphatase calcineurin and promoting the general amino acid control (GAAC) response...
November 29, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27895176/the-syk-nfat-il-2-pathway-in-dendritic-cells-is-required-for-optimal-sterile-immunity-elicited-by-alum-adjuvants
#10
Hanif Javanmard Khameneh, Adrian W S Ho, Roberto Spreafico, Heidi Derks, Hazel Q Y Quek, Alessandra Mortellaro
Despite a long history and extensive usage of insoluble aluminum salts (alum) as vaccine adjuvants, the molecular mechanisms underpinning Ag-specific immunity upon vaccination remain unclear. Dendritic cells (DCs) are crucial initiators of immune responses, but little is known about the molecular pathways used by DCs to sense alum and, in turn, activate T and B cells. In this article, we show that alum adjuvanticity requires IL-2 specifically released by DCs, even when T cell secretion of IL-2 is intact. We demonstrate that alum, as well as other sterile particulates, such as uric acid crystals, induces DCs to produce IL-2 following initiation of actin-mediated phagocytosis that leads to Src and Syk kinase activation, Ca(2+) mobilization, and calcineurin-dependent activation of NFAT, the master transcription factor regulating IL-2 expression...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27892464/wnt5a-induces-renal-aqp2-expression-by-activating-calcineurin-signalling-pathway
#11
Fumiaki Ando, Eisei Sohara, Tetsuji Morimoto, Naofumi Yui, Naohiro Nomura, Eriko Kikuchi, Daiei Takahashi, Takayasu Mori, Alain Vandewalle, Tatemitsu Rai, Sei Sasaki, Yoshiaki Kondo, Shinichi Uchida
Heritable nephrogenic diabetes insipidus (NDI) is characterized by defective urine concentration mechanisms in the kidney, which are mainly caused by loss-of-function mutations in the vasopressin type 2 receptor. For the treatment of heritable NDI, novel strategies that bypass the defective vasopressin type 2 receptor are required to activate the aquaporin-2 (AQP2) water channel. Here we show that Wnt5a regulates AQP2 protein expression, phosphorylation and trafficking, suggesting that Wnt5a is an endogenous ligand that can regulate AQP2 without the activation of the classic vasopressin/cAMP signalling pathway...
November 28, 2016: Nature Communications
https://www.readbyqxmd.com/read/27891136/characterization-of-salinity-tolerance-of-transgenic-rice-lines-harboring-hscbl8-of-wild-barley-hordeum-spontanum-line-from-qinghai-tibet-plateau
#12
Wanli Guo, Tianlong Chen, Nazim Hussain, Guoping Zhang, Lixi Jiang
Rice is more sensitive to salinity, particularly at its early vegetative and later productive stages. Wild plants growing in harsh environments such as wild barley from Qinghai-Tibet Plateau adapt to the adverse environment with allelic variations at the loci responsible for stressful environment, which could be used for rice genetic improvement. In this study, we overexpressed HsCBL8 encoding a calcium-sensor calcineurin B-like (CBL) protein in rice. The gene was isolated from XZ166, a wild-barley (Hordeum spontanum) line originated from Qinghai-Tibet Plateau...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27890789/cyclosporin-derivatives-inhibit-hepatitis-b-virus-entry-without-interfering-the-ntcp-transporter
#13
Satomi Shimura, Koichi Watashi, Kento Fukano, Michael Peel, Ann Sluder, Fumihiro Kawai, Masashi Iwamoto, Senko Tsukuda, Junko S Takeuchi, Takeshi Miyake, Masaya Sugiyama, Yuki Ogasawara, Sam-Yong Park, Yasuhito Tanaka, Hiroyuki Kusuhara, Masashi Mizokami, Camille Sureau, Takaji Wakita
BACKGROUND&AIMS: Most of the specific inhibitors of hepatitis B virus (HBV) entry, including myrcludex-B and cyclosporin A (CsA), target an HBV entry receptor, sodium taurocholate cotransporting polypeptide (NTCP). As all these agents have capacities to impair the NTCP transporter activity for bile acid uptake and thus may cause significant adverse effects, we aim to identify small molecules that inhibit HBV entry but least affecting the NTCP transporter function. METHODS: We focused on derivatives of CsA, which originally inhibited both HBV entry and NTCP-mediated bile acid uptake, to analyze the possibility to distinguish these two activities...
November 24, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27889299/safety-and-efficacy-outcomes-3-years-after-switching-to-belatacept-from-a-calcineurin-inhibitor-in-kidney-transplant-recipients-results-from-a-phase-2-randomized-trial
#14
Josep M Grinyó, Maria Del Carmen Rial, Josefina Alberu, Steven M Steinberg, Roberto C Manfro, Georgy Nainan, Flavio Vincenti, Charlotte Jones-Burton, Nassim Kamar
BACKGROUND: In a phase 2 study, kidney transplant recipients of low immunologic risk who switched from a calcineurin inhibitor (CNI) to belatacept had improved kidney function at 12 months postconversion versus those continuing CNI therapy, with a low rate of acute rejection and no transplant loss. STUDY DESIGN: 36-month follow-up of the intention-to-treat population. SETTING & PARTICIPANTS: CNI-treated adult kidney transplant recipients with stable transplant function (estimated glomerular filtration rate [eGFR], 35-75mL/min/1...
November 23, 2016: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/27888551/selective-targeting-of-high-affinity-lfa-1-does-not-augment-costimulation-blockade-in-a-nonhuman-primate-renal-transplantation-model
#15
K P Samy, D A Anderson, D J Lo, M S Mulvihill, M Song, A B Farris, B S Parker, A L MacDonald, C Lu, T A Springer, S C Kachlany, K A Reimann, T How, F V Leopardi, K S Franke, K D Williams, B H Collins, A D Kirk
Costimulation blockade (CoB) via belatacept is a lower morbidity alternative to calcineurin inhibitor (CNI)-based immunosuppression. However, it has higher rates of early acute rejection. These early rejections are mediated in part by memory T cells, which have reduced dependence on the pathway targeted by belatacept, and increased adhesion molecule expression. One such molecule is Leukocyte Function Associated Antigen (LFA)-1. LFA-1 exists in two forms, a commonly expressed, low-affinity form, and a transient, high-affinity form, expressed only during activation...
November 26, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27886903/allergic-contact-dermatitis
#16
REVIEW
Lisa Kostner, Florian Anzengruber, Caroline Guillod, Mike Recher, Peter Schmid-Grendelmeier, Alexander A Navarini
Allergic contact dermatitis (ACD) is a common skin disease caused by a T cell-mediated immune reaction to usually innocuous allergens. ACD can have grave medical and socioeconomic consequences. ACD and irritant contact dermatitis often occur together. A detailed history and clinical examination are crucial and guide patch testing, which is the gold standard to diagnose ACD. T-cell clones persisting in the skin may explain the tendency of ACD to relapse even after years of allergen avoidance. Traditional treatments for ACD are topical steroids, calcineurin inhibitors, phototherapy, retinoids (including the recent alitretinoin), and immunosuppressants...
February 2017: Immunology and Allergy Clinics of North America
https://www.readbyqxmd.com/read/27881351/-role-of-can-nfatc3-pathway-in-abdominal-aorta-restenosis-following-ballon-dilatation-in-rats
#17
Xiao-Yun Li, Long-Gen Xiong, De-En Li, Lu-Ning Zhao, Qi Dong
OBJECTIVE: To investegate the role of calcineurin (CaN) and its downstream nuclear factor of activated T-cells (NFATc3) in abdominal aorta restenosis following balloon dilatation in rats. METHODS: SD rats were randomly divided into sham-operated group, balloon group and cyclosporine A (CsA) group. The rats in the latter two groups were subjected to abdominal aorta injury with balloon dilatation, and those in CsA group were treated with CsA at the daily dose of 12...
November 20, 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/27879314/genetic-variation-in-the-slc8a1-calcium-signaling-pathway-is-associated-with-susceptibility-to-kawasaki-disease-and-coronary-artery-abnormalities
#18
Chisato Shimizu, Hariklia Eleftherohorinou, Victoria J Wright, Jihoon Kim, Martin P Alphonse, James C Perry, Rolando Cimaz, David Burgner, Nagib Dahdah, Long T Hoang, Chiea-Chuen Khor, Andrea Salgado, Adriana H Tremoulet, Sonia Davila, Taco W Kuijpers, Martin L Hibberd, Todd A Johnson, Atsushi Takahashi, Tatsuhiko Tsunoda, Michiaki Kubo, Toshihiro Tanaka, Yoshihiro Onouchi, Rae S M Yeung, Lachlan J M Coin, Michael Levin, Jane C Burns
BACKGROUND: -Kawasaki disease (KD) is an acute pediatric vasculitis in which host genetics influence both susceptibility to KD and the formation of coronary artery aneurysms. Variants discovered by genome-wide association studies (GWAS) and linkage studies only partially explain the influence of genetics on KD susceptibility. METHODS AND RESULTS: -To search for additional functional genetic variation, we performed pathway and gene stability analysis on a GWAS dataset...
November 21, 2016: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/27873464/hyalinosis-lesions-in-renal-transplant-biopsies-time-dependent-complexity-of-interpretation
#19
Gunilla Einecke, Jeff Reeve, Philip F Halloran
Because calcineurin inhibitor immunosuppressive drugs (CNIs) induce arteriolar hyalinosis (ah) in kidney transplants, ah lesions can potentially provide information about drug exposure. We studied the relationship of ah lesions to findings and outcomes in 562 indication biopsies taken 3 days to 35 years post-transplant. Prevalence of ah lesions increased with time post-transplant (TxBx). Ah-scores correlated with arterial intimal thickening and atrophy-fibrosis but, unlike atrophy-fibrosis, did not increase until after 500 days because of a background of ah1 lesions in early biopsies reflecting donor aging...
November 22, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27872486/alpha-2-macroglobulin-in-alzheimer-s-disease-a-marker-of-neuronal-injury-through-the-rcan1-pathway
#20
V R Varma, S Varma, Y An, T J Hohman, S Seddighi, R Casanova, A Beri, E B Dammer, N T Seyfried, O Pletnikova, A Moghekar, M R Wilson, J J Lah, R J O'Brien, A I Levey, J C Troncoso, M S Albert, M Thambisetty
Preclinical changes that precede the onset of symptoms and eventual diagnosis of Alzheimer's disease (AD) are a target for potential preventive interventions. A large body of evidence suggests that inflammation is closely associated with AD pathogenesis and may be a promising target pathway for such interventions. However, little is known about the association between systemic inflammation and preclinical AD pathophysiology. We first examined whether the acute-phase protein, alpha-2 macroglobulin (A2M), a major component of the innate immune system, was associated with cerebrospinal fluid (CSF) markers of neuronal injury in preclinical AD and risk of incident AD in the predictors of cognitive decline among normal individuals (BIOCARD) cohort...
November 22, 2016: Molecular Psychiatry
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