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https://www.readbyqxmd.com/read/27928873/lycopene-inhibits-regulator-of-calcineurin-1-mediated-apoptosis-by-reducing-oxidative-stress-and-down-regulating-nucling-in-neuronal-cells
#1
Seiyoung Lim, Sinwoo Hwang, Ji Hoon Yu, Joo Weon Lim, Hyeyoung Kim
SCOPE: Regulator of calcineurin 1 (RCAN1) is located on the Down syndrome critical region (DSCR) locus in human chromosome 21. Oxidative stress and overexpression of RCAN1 is implicated in neuronal impairment in Down's syndrome (DS) and Alzheimer's disease (AD). Serum level of lycopene, an antioxidant pigment, is low in DS and AD patients, which may be related to neuronal damage. The present study is to investigate whether lycopene inhibits apoptosis by reducing ROS levels, NF-κB activation, expression of the apoptosis regulator Nucling, cell viability, and indices of apoptosis (cytochrome c release, caspase-3 activation) in RCAN1-overexpressing neuronal cells...
December 8, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27917924/rcans-regulate-the-convergent-roles-of-nfatc1-in-bone-homeostasis
#2
Jung Ha Kim, Kabsun Kim, Inyoung Kim, Semun Seong, Byung-Chul Jeong, Kwang-Il Nam, Kyung Keun Kim, Jeffery D Molkentin, Nacksung Kim
Activation of calcineurin-dependent nuclear factor of activated T cells c1 (NFATc1) is convergent for normal bone homeostasis. NFATc1 regulates both osteoclastogenesis and osteoblastogenesis. Here we investigated the roles of regulator of calcineurin (RCAN) genes in bone homeostasis. RCANs function as potent physiological inhibitors of calcineurin. Overexpression of RCANs in osteoclast precursor cells attenuated osteoclast differentiation, while their overexpression in osteoblasts enhanced osteoblast differentiation and function...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27873103/differential-regulation-of-angiogenic-cellular-processes-and-claudin-5-by-histamine-and-vegf-via-pi3k-signaling-transcription-factor-snai2-and-interleukin-8
#3
Johanna P Laakkonen, Jari P Lappalainen, Thomas L Theelen, Pyry I Toivanen, Tiina Nieminen, Suvi Jauhiainen, Minna U Kaikkonen, Judith C Sluimer, Seppo Ylä-Herttuala
AIMS: Histamine and vascular endothelial growth factor A (VEGF) are central regulators in vascular pathologies. Their gene regulation leading to vascular remodeling has remained obscure. In this study, EC regulation mechanisms of histamine and VEGF were compared by RNA sequencing of primary endothelial cells (ECs), functional in vitro assays and in vivo permeability mice model. METHODS AND RESULTS: By RNA sequencing, similar transcriptional alterations of genes involved in activation of primary ECs, cell proliferation and adhesion were observed between histamine and VEGF...
November 21, 2016: Angiogenesis
https://www.readbyqxmd.com/read/27872486/alpha-2-macroglobulin-in-alzheimer-s-disease-a-marker-of-neuronal-injury-through-the-rcan1-pathway
#4
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
https://www.readbyqxmd.com/read/27871170/allele-specific-phenotype-suggests-a-possible-stimulatory-activity-of-rcan-1-on-calcineurin-in-caenorhabditis-elegans
#5
Weixun Li, Tae-Woo Choi, Joohong Ahnn, Sun-Kyung Lee
Regulator of calcineurin 1 (RCAN1) binds to calcineurin through the PxIxIT motif, which is evolutionarily conserved. SP repeat phosphorylation in RCAN1 is required for its complete function. The specific interaction between RCAN1 and calcineurin is critical for calcium/calmodulin-dependent regulation of calcineurin serine/threonine phosphatase activity. In this study, we investigated two available deletion rcan-1 mutants in Caenorhabditis elegans, which proceed differently for transcription and translation...
November 30, 2016: Molecules and Cells
https://www.readbyqxmd.com/read/27861892/the-regulator-of-calcineurin-1-increases-adenine-nucleotide-translocator-1-and-leads-to-mitochondrial-dysfunctions
#6
Hui Jiang, Chen Zhang, Yu Tang, Juan Zhao, Tan Wang, Heng Liu, Xiulian Sun
The overexpression of regulator of calcineurin 1 isoform 1 (RCAN1.1) has been implicated in mitochondrial dysfunctions of Alzheimer's disease (AD); however, the mechanism linking RCAN1.1 overexpression and the mitochondrial dysfunctions remains unknown. In this study, we use human neuroblastoma SH-SY5Y cells stably expressing RCAN1.1S and rat primary neurons infected with RCAN1.1S expression lentivirus to study the association of RCAN1 with mitochondrial functions. Our study here showed that the overexpression of RCAN1...
November 15, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27789290/ablation-of-biglycan-attenuates-cardiac-hypertrophy-and-fibrosis-after-left-ventricular-pressure-overload
#7
Nadine Beetz, Carolin Rommel, Tilman Schnick, Elena Neumann, Achim Lother, Elsa Beatriz Monroy-Ordonez, Martin Zeeb, Sebastian Preissl, Ralf Gilsbach, Ariane Melchior-Becker, Bartosz Rylski, Monika Stoll, Liliana Schaefer, Friedhelm Beyersdorf, Brigitte Stiller, Lutz Hein
AIMS: Biglycan, a small leucine-rich proteoglycan, has been shown to play an important role in stabilizing fibrotic scars after experimental myocardial infarction. However, the role of biglycan in the development and regression of cardiomyocyte hypertrophy and fibrosis during cardiac pressure overload and unloading remains elusive. Thus, the aim of the present study was to assess the effect of biglycan on cardiac remodeling in a mouse model of left ventricular pressure overload and unloading...
October 24, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27688314/genotype-dependent-and-independent-calcium-signaling-dysregulation-in-human-hypertrophic-cardiomyopathy
#8
Adam S Helms, Francisco J Alvarado, Jaime Yob, Vi T Tang, Francis Pagani, Mark W Russell, Héctor H Valdivia, Sharlene M Day
BACKGROUND: Aberrant calcium signaling may contribute to arrhythmias and adverse remodeling in hypertrophic cardiomyopathy (HCM). Mutations in sarcomere genes may distinctly alter calcium handling pathways. METHODS: We analyzed gene expression, protein levels, and functional assays for calcium regulatory pathways in human HCM surgical samples with (n=25) and without (n=10) sarcomere mutations compared with control hearts (n=8). RESULTS: Gene expression and protein levels for calsequestrin, L-type calcium channel, sodium-calcium exchanger, phospholamban, calcineurin, and calcium/calmodulin-dependent protein kinase type II (CaMKII) were similar in HCM samples compared with controls...
November 29, 2016: Circulation
https://www.readbyqxmd.com/read/27597899/the-emerging-roles-of-the-calcineurin-nuclear-factor-of-activated-t-lymphocytes-pathway-in-nervous-system-functions-and-diseases
#9
REVIEW
Maulilio John Kipanyula, Wahabu Hamisi Kimaro, Paul F Seke Etet
The ongoing epidemics of metabolic diseases and increase in the older population have increased the incidences of neurodegenerative diseases. Evidence from murine and cell line models has implicated calcineurin-nuclear factor of activated T-lymphocytes (NFAT) signaling pathway, a Ca(2+)/calmodulin-dependent major proinflammatory pathway, in the pathogenesis of these diseases. Neurotoxins such as amyloid-β, tau protein, and α-synuclein trigger abnormal calcineurin/NFAT signaling activities. Additionally increased activities of endogenous regulators of calcineurin like plasma membrane Ca(2+)-ATPase (PMCA) and regulator of calcineurin 1 (RCAN1) also cause neuronal and glial loss and related functional alterations, in neurodegenerative diseases, psychotic disorders, epilepsy, and traumatic brain and spinal cord injuries...
2016: Journal of Aging Research
https://www.readbyqxmd.com/read/27449908/rcan1-deficiency-protects-against-salmonella-intestinal-infection-by-modulating-jnk-activation
#10
Qian-Qian Lei, Gui-Qiu Hu, Wei Chen, Shui-Xing Yu, Shuai Qi, Chong-Tao Du, Jing-Min Gu, Tong-Jun Lin, Yong-Jun Yang
OBJECTIVE: RCAN1 (regulator of calcineurin 1) has been shown to be involved in various physiological and pathological processes. However, the biological implications of RCAN1 during gastrointestinal tract infection remain unclear. In this study, we tried to determine the role of RCAN1 in acute Salmonella infectious colitis. METHODS: Wild type and RCAN1-deficient mice or macrophages were used to characterize the impacts of RCAN1 on intestinal inflammation, inflammatory cytokines production, animal survival, and pathogen clearance following Salmonella challenge...
September 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27403036/regulator-of-calcineurin-1-in-periodontal-disease
#11
Ulrike Peters, Eleni Solominidou, Yüksel Korkmaz, Stefan Rüttermann, Astrid Klocke, Thomas Frank Flemmig, Thomas Beikler
Nuclear factor of activated T-cells (NFAT) and NF-kB pathway associated processes are involved in the pathogenesis of various inflammatory disorders, for example, periodontal disease. The activation of these pathways is controlled by the regulator of calcineurin 1 (RCAN1). The aim of this study was to elucidate the role of RCAN1 in periodontal disease. Healthy and inflamed periodontal tissues were analyzed by immunohistochemistry and immunofluorescence using specific rabbit polyclonal anti-RCAN1 antibodies...
2016: Mediators of Inflammation
https://www.readbyqxmd.com/read/27339639/critical-role-of-regulator-of-calcineurin-1-in-spinal-cord-injury
#12
Guodong Wang, Yilei Zhao, Shenpeng Liu, Jinling Jia, Tan Lu
Spinal cord injury (SCI) is a severe clinical problem worldwide. The pathogenesis of SCI is complicated and much is unknown. The current study was designed to investigate the possible role of regulator of calcineurin 1 (RCAN1) in SCI and to explore the possible molecular mechanisms. Rats were injected with LVshRNAi-RCAN1 and then contusion-induced SCI was established. We found that RCAN1 was significantly increased in spinal cord of rats with SCI. Knockdown of RCAN1 markedly facilitated the structural and functional recovery in the spinal cord, as illustrated by decrease of lesion volume and increase of Basso, Beattie, and Bresnahan (BBB) and combined behavioral score (CBS) scores...
December 2016: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/27195491/a-syntenic-cross-species-aneuploidy-genetic-screen-links-rcan1-expression-to-%C3%AE-cell-mitochondrial-dysfunction-in-type-2-diabetes
#13
Heshan Peiris, Michael D Duffield, Joao Fadista, Claire F Jessup, Vinder Kashmir, Amanda J Genders, Sean L McGee, Alyce M Martin, Madiha Saiedi, Nicholas Morton, Roderick Carter, Michael A Cousin, Alexandros C Kokotos, Nikolay Oskolkov, Petr Volkov, Tertius A Hough, Elizabeth M C Fisher, Victor L J Tybulewicz, Jorge Busciglio, Pinar E Coskun, Ann Becker, Pavel V Belichenko, William C Mobley, Michael T Ryan, Jeng Yie Chan, D Ross Laybutt, P Toby Coates, Sijun Yang, Charlotte Ling, Leif Groop, Melanie A Pritchard, Damien J Keating
Type 2 diabetes (T2D) is a complex metabolic disease associated with obesity, insulin resistance and hypoinsulinemia due to pancreatic β-cell dysfunction. Reduced mitochondrial function is thought to be central to β-cell dysfunction. Mitochondrial dysfunction and reduced insulin secretion are also observed in β-cells of humans with the most common human genetic disorder, Down syndrome (DS, Trisomy 21). To identify regions of chromosome 21 that may be associated with perturbed glucose homeostasis we profiled the glycaemic status of different DS mouse models...
May 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27130438/protein-degradation-in-a-lamp-2-deficient-b-lymphoblastoid-cell-line-from-a-patient-with-danon-disease
#14
Raul Sánchez-Lanzas, Beatriz Alvarez-Castelao, Teresa Bermejo, Teresa Ayuso, Teresa Tuñón, José G Castaño
Danon disease, a condition characterized by cardiomyopathy, myopathy, and intellectual disability, is caused by mutations in the LAMP-2 gene. Lamp-2A protein, generated by alternative splicing from the Lamp-2 pre-mRNA, is reported to be the lysosomal membrane receptor essential for the chaperone-mediated autophagic pathway (CMA) aimed to selective protein targeting and translocation into the lysosomal lumen for degradation. To study the relevance of Lamp-2 in protein degradation, a lymphoblastoid cell line was obtained by EBV transformation of B-cells from a Danon patient...
August 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27109380/quercetin-targets-the-interaction-of-calcineurin-with-lxvp-type-motifs-in-immunosuppression
#15
Yane Zhao, Jin Zhang, Xiaoyu Shi, Jing Li, Rui Wang, Ruiwen Song, Qun Wei, Huaibin Cai, Jing Luo
Calcineurin (CN) is a unique calcium/calmodulin (CaM)-activated serine/threonine phosphatase. To perform its diverse biological functions, CN communicates with many substrates and other proteins. In the physiological activation of T cells, CN acts through transcriptional factors belonging to the NFAT family and other transcriptional effectors. The classic immunosuppressive drug cyclosporin A (CsA) can bind to cyclophilin (CyP) and compete with CN for the NFAT LxVP motif. CsA has debilitating side effects, including nephrotoxicity, hypertension and tremor...
August 2016: Biochimie
https://www.readbyqxmd.com/read/26713664/targeting-myocardial-reperfusion-injuries-with-cyclosporine-in-the-circus-trial-pharmacological-reasons-for-failure
#16
Laurent Monassier, Estelle Ayme-Dietrich, Gaëlle Aubertin-Kirch, Atul Pathak
The mitochondrial permeability transition (mPTP) is a key feature of cardiac cell death in ischaemia-reperfusion injury (I/R). The mPTP blocker, cyclosporine A (CsA), has been shown to give protection against reperfusion-induced myocardial necrosis and troubles generated by acute coronary artery repermeabilization. Nevertheless, the results of the CIRCUS trial (Does Cyclosporine Improve Clinical Outcome in ST-Elevation Myocardial Infarction Patients) seem to go against this hypothesis. Pharmacological reasons linked to CsA pharmacokinetics and pharmacodynamics could be suggested...
April 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/26658127/rcan1-links-impaired-neurotrophin-trafficking-to-aberrant-development-of-the-sympathetic-nervous-system-in-down-syndrome
#17
Ami Patel, Naoya Yamashita, Maria Ascaño, Daniel Bodmer, Erica Boehm, Chantal Bodkin-Clarke, Yun Kyoung Ryu, Rejji Kuruvilla
Down syndrome is the most common chromosomal disorder affecting the nervous system in humans. To date, investigations of neural anomalies in Down syndrome have focused on the central nervous system, although dysfunction of the peripheral nervous system is a common manifestation. The molecular and cellular bases underlying peripheral abnormalities have remained undefined. Here, we report the developmental loss of sympathetic innervation in human Down syndrome organs and in a mouse model. We show that excess regulator of calcineurin 1 (RCAN1), an endogenous inhibitor of the calcineurin phosphatase that is triplicated in Down syndrome, impairs neurotrophic support of sympathetic neurons by inhibiting endocytosis of the nerve growth factor (NGF) receptor, TrkA...
December 14, 2015: Nature Communications
https://www.readbyqxmd.com/read/26497675/rcan1-overexpression-promotes-age-dependent-mitochondrial-dysregulation-related-to-neurodegeneration-in-alzheimer-s-disease
#18
Helen Wong, Josien Levenga, Peter Cain, Beverly Rothermel, Eric Klann, Charles Hoeffer
Aging is the largest risk factor for Alzheimer's disease (AD). Patients with Down syndrome (DS) develop symptoms consistent with early-onset AD, suggesting that overexpression of chromosome 21 genes such as Regulator of Calcineurin 1 (RCAN1) plays a role in AD pathogenesis. RCAN1 levels are increased in the brain of DS and AD patients but also in the human brain with normal aging. RCAN1 has been implicated in several neuronal functions, but whether its increased expression is correlative or causal in the aging-related progression of AD remains elusive...
December 2015: Acta Neuropathologica
https://www.readbyqxmd.com/read/26492364/the-rcan1-inhibits-nf-%C3%AE%C2%BAb-and-suppresses-lymphoma-growth-in-mice
#19
C Liu, L Zheng, H Wang, X Ran, H Liu, X Sun
Nuclear factor-κB (NF-κB) has a vital role in cell survival. Inhibition of NF-κB has been proven to be an efficient therapeutic pathway for various cancers. Activation of NF-κB is mainly through serine residues' phosphorylation of inhibitor of κBα (IκBα) by IKK complex. Phosphorylation at tyrosine 42 is an alternative pathway in regulation of IκBα and NF-κB signaling, though little is known about the underlying mechanism. Here we identified regulator of calcineurin 1 (RCAN1) as a novel endogenous inhibitor of NF-κB signaling pathway...
October 22, 2015: Cell Death & Disease
https://www.readbyqxmd.com/read/26461328/acute-electrical-pulse-stimulation-and-hyperglycemia-regulates-rcan1-4-in-c2c12-myotubes-through-oxidative-stress
#20
Ramin Emrani Bidi, Amelie Rebillard, Dany Saligaut, Arlette Delamarche, Kelvin J A Davies, Josiane Cillard
Regulator of Calcineurin1 (RCAN1) controls the Sr/Thr phosphatase, Calcineurin. RCAN1 has never been studied in-vitro in myotubes following acute Electrical Pulse Stimulation (EPS) which recapitulates the physiological effect of exhaustive exercise and hyperglycemia (HG). 144 h differentiated C2C12 myotubes were treated either with high glucose (HG) at 15mM or kept as control for 48 h. The myotubes were subjected to EPS for 1second followed by 1second of pause for 90min. Two separate Non-EPS controls with and without HG were performed simultaneously...
October 2014: Free Radical Biology & Medicine
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