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https://www.readbyqxmd.com/read/29104573/endothelial-regulator-of-calcineurin-1-promotes-barrier-integrity-and-modulates-histamine-induced-barrier-dysfunction-in-anaphylaxis
#1
Constanza Ballesteros-Martinez, Nerea Mendez-Barbero, Alma Montalvo-Yuste, Bettina M Jensen, Aída Gomez-Cardenosa, Lotte Klitfod, María Garrido-Arandia, Gloria Alvarez-Llamas, Carlos Pastor-Vargas, Fernando Vivanco, Lene Heise Garvey, Javier Cuesta-Herranz, Lars K Poulsen, Vanesa Esteban
Anaphylaxis, the most serious and life-threatening allergic reaction, produces the release of inflammatory mediators by mast cells and basophils. Regulator of calcineurin 1 (Rcan1) is a negative regulator of mast-cell degranulation. The action of mediators leads to vasodilation and an increase in vascular permeability, causing great loss of intravascular volume in a short time. Nevertheless, the molecular basis remains unexplored on the vascular level. We investigated Rcan1 expression induced by histamine, platelet-activating factor (PAF), and epinephrine in primary human vein (HV)-/artery (HA)-derived endothelial cells (ECs) and human dermal microvascular ECs (HMVEC-D)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29094385/the-neuronal-and-endocrine-roles-of-rcan1-in-health-and-disease
#2
Heshan Peiris, Damien J Keating
Regulator of calcineurin 1 (RCAN1) was first discovered as a gene located on human chromosome 21, expressed in neurons and overexpressed in the brains of Down Syndrome individuals. Increased expression of RCAN1 has been linked with not only Down Syndrome-associated pathology but also an associated neurological disorder, Alzheimer's Disease, in which neuronal RCAN1 expression is also increased. RCAN1 has additionally been demonstrated to effect other cell types including endocrine cells, with links to the pathogenesis of β-cell dysfunction in type 2 diabetes...
November 1, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28993896/rcan1-mutation-and-functional-characterization-in-children-with-sporadic-congenital-heart-disease
#3
Xiaoyong Li, Lei Shi, Ming Xu, Xun Zheng, Yiwen Yu, Jing Jin
Congenital heart disease (CHD) is the most frequent birth defect. RCAN1 (regulator of calcineurin 1) contributes to CHD in Down syndrome. However, whether RCAN1 is also associated with nonsyndromic CHD remains unclear. This study sequenced the exons and flanking region of RCAN1 in 128 sporadic CHD patients and 150 normal controls. We identified six novel heterozygous mutations in CHD patients. Functional assay showed that the g.482G>T could obviously raise the promoter activity of RCAN1.4 in vitro; However, we failed to detect the expression of RCAN1 in the right auricle, which made it confused to evaluate the pathogenicity of this mutation...
October 9, 2017: Pediatric Cardiology
https://www.readbyqxmd.com/read/28756311/neurogenesis-impairment-an-early-developmental-defect-in-down-syndrome
#4
REVIEW
Fiorenza Stagni, Andrea Giacomini, Marco Emili, Sandra Guidi, Renata Bartesaghi
Down syndrome (DS) is characterized by brain hypotrophy and intellectual disability starting from early life stages. Accumulating evidence shows that the phenotypic features of the DS brain can be traced back to the fetal period since the DS brain exhibits proliferation potency reduction starting from the critical time window of fetal neurogenesis. This defect is worsened by the fact that neural progenitor cells exhibit reduced acquisition of a neuronal phenotype and an increase in the acquisition of an astrocytic phenotype...
July 26, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28751455/calcineurin-dysregulation-underlies-spinal-cord-injury-induced-k-channel-dysfunction-in-drg-neurons
#5
Benjamin M Zemel, Tanziyah Muqeem, Eric V Brown, Miguel Goulão, Mark W Urban, Stephen R Tymanskyj, Angelo C Lepore, Manuel Covarrubias
Dysfunction of the fast-inactivating Kv3.4 potassium current in dorsal root ganglion (DRG) neurons contributes to the hyperexcitability associated with persistent pain induced by spinal cord injury (SCI). However, the underlying mechanism is not known. In light of our previous work demonstrating modulation of the Kv3.4 channel by phosphorylation, we investigated the role of the phosphatase calcineurin (CaN) using electrophysiological, molecular, and imaging approaches in adult female Sprague Dawley rats. Pharmacological inhibition of CaN in small-diameter DRG neurons slowed repolarization of the somatic action potential (AP) and attenuated the Kv3...
August 23, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28712932/pyrrolidine-dithiocarbamate-pdtc-inhibits-inflammatory-signaling-via-expression-of-regulator-of-calcineurin-activity-1-rcan1-anti-inflammatory-mechanism-of-pdtc-through-rcan1-induction
#6
Eun Hye Lee, Seon Sook Kim, Su Ryeon Seo
Pyrrolidine dithiocarbamate (PDTC) is a thiol compound that elicits anti-inflammatory effects by inhibiting NF-κB signaling. In this study, we report that regulator of calcineurin activity 1 (RCAN1) expression is induced by PDTC treatment and that increased RCAN1 expression is dependent on the generation of reactive oxygen species (ROS) and activation of p38 MAPK and JNK signaling. We also report that the ability of PDTC to induce RCAN1 is mediated by activator protein-1 (AP-1)-dependent gene transcription, and identified a functional AP-1 binding site in the RCAN1 promoter by producing mutations and conducting chromatin immunoprecipitation (ChIP) analyses...
November 1, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28631570/the-effect-of-rcan1-on-the-biological-behaviors-of-small-cell-lung-cancer
#7
Ningqiang Ma, Weiwei Shen, Hailin Pang, Ning Zhang, Hong Shi, Jianlin Wang, Helong Zhang
Bone is the third most common site of cancer metastasis. In total, 30%-40% of lung cancer cases can develop skeletal metastasis for which no effective therapy in clinic is available. RCAN1 (regulator of calcineurin 1) is an important regulator in angiogenesis which is vital to tumor growth. In this study, we investigated the changes of biological behaviors in SBC-5 and SBC-3 cells after the RCAN1 expression level was changed. Briefly, overexpression of RCAN1 significantly attenuated their malignancy, including decreased ability of proliferation, colony formation, migration, invasion, and bone adherence...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28583823/regulator-of-calcineurin-1-gene-isoform-4-down-regulated-in-hepatocellular-carcinoma-prevents-proliferation-migration-and-invasive-activity-of-cancer-cells-and-metastasis-of-orthotopic-tumors-by-inhibiting-nuclear-translocation-of-nfat1
#8
Haojie Jin, Cun Wang, Guangzhi Jin, Haoyu Ruan, Dishui Gu, Lin Wei, Hui Wang, Ning Wang, Einthavy Arunachalam, Yurong Zhang, Xuan Deng, Chen Yang, Yi Xiong, Hugang Feng, Ming Yao, Jingyuan Fang, Jianren Gu, Wenming Cong, Wenxin Qin
BACKGROUND & AIMS: Individuals with Down syndrome have a low risk for many solid tumors, prompting the search for tumor suppressor genes on human chromosome 21 (HSA21). We aimed to identify and explore potential mechanisms of tumor suppressors on HSA21 in hepatocellular carcinoma (HCC). METHODS: We compared expression of HSA21 genes in 14 pairs of primary HCC and adjacent noncancer liver tissues using the Affymetrix HG-U133 Plus 2.0 array (Affymetrix, Santa Clara, CA)...
September 2017: Gastroenterology
https://www.readbyqxmd.com/read/28553204/leucine-rich-repeat-kinase-2-lrrk2-stimulates-il-1%C3%AE-mediated-inflammatory-signaling-through-phosphorylation-of-rcan1
#9
Kyung A Han, Lang Yoo, Jee Y Sung, Sun A Chung, Ji W Um, Hyeyoung Kim, Wongi Seol, Kwang C Chung
Leucine-rich repeat kinase 2 (LRRK2) is a Ser/Thr kinase having mixed lineage kinase-like and GTPase domains, controlling neurite outgrowth and neuronal cell death. Evidence suggests that LRRK2 is involved in innate immune response signaling, but the underlying mechanism is yet unknown. A novel protein inhibitor of phosphatase 3B, RCAN1, is known to positively regulate inflammatory signaling through modulation of several intracellular targets of interleukins in immune cells. In the present study, we report that LRRK2 phosphorylates RCAN1 (RCAN1-1S) and is markedly up-regulated during interleukin-1β (IL-1β) treatment...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28369518/misregulation-of-calcium-handling-proteins-promotes-hyperactivation-of-calcineurin-nfat-signaling-in-skeletal-muscle-of-dm1-mice
#10
Aymeric Ravel-Chapuis, Guy Bélanger, Jocelyn Côté, Robin N Michel, Bernard J Jasmin
Myotonic Dystrophy type 1 (DM1) is caused by an expansion of CUG repeats in DMPK mRNAs. This mutation affects alternative splicing through misregulation of RNA-binding proteins. Amongst pre-mRNAs that are mis-spliced, several code for proteins involved in calcium homeostasis suggesting that calcium-handling and signaling are perturbed in DM1. Here, we analyzed expression of such proteins in DM1 mouse muscle. We found that the levels of several sarcoplasmic reticulum proteins (SERCA1, sarcolipin and calsequestrin) are altered, likely contributing to an imbalance in calcium homeostasis...
June 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28292468/microrna-34a-targets-regulator-of-calcineurin-1-to-modulate-endothelial-inflammation-after-fetal-cardiac-bypass-in-goat-placenta
#11
Hai-Yun Yuan, Cheng-Bin Zhou, Ji-Mei Chen, Xiao-Bing Liu, Shu-Sheng Wen, Gang Xu, Jian Zhuang
INTRODUCTION: Placental dysfunction characterized by vascular endothelial inflammation is one of the most notable responses to fetal cardiac bypass. Regulator of calcineurin 1 (RCAN1) is an important regulator of inflammatory responses. MicroRNAs (miRNAs) are essential post-transcriptional modulators of gene expression, and miRNA-34a (miR-34a) was showed to activate vascular endothelial inflammation. We hypothesized that miR-34a may be a key regulator of placental dysfunction after fetal cardiac bypass...
March 2017: Placenta
https://www.readbyqxmd.com/read/28289712/rcan1-4-is-a-thyroid-cancer-growth-and-metastasis-suppressor
#12
Chaojie Wang, Motoyasu Saji, Steven E Justiniano, Adlina Mohd Yusof, Xiaoli Zhang, Lianbo Yu, Soledad Fernández, Paul Wakely, Krista La Perle, Hiroshi Nakanishi, Neal Pohlman, Matthew D Ringel
Metastasis suppressors are key regulators of tumor growth, invasion, and metastases. Loss of metastasis suppressors has been associated with aggressive tumor behaviors and metastatic progression. We previously showed that regulator of calcineurin 1, isoform 4 (RCAN1-4) was upregulated by the KiSS1 metastatic suppression pathway and could inhibit cell motility when overexpressed in cancer cells. To test the effects of endogenous RCAN1-4 loss on thyroid cancer in vivo, we developed RCAN1-4 knockdown stable cells...
March 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28271280/rcan1-4-regulates-vegfr-2-internalisation-cell-polarity-and-migration-in-human-microvascular-endothelial-cells
#13
Ahmad F Alghanem, Emma L Wilkinson, Maxine S Emmett, Mohammad A Aljasir, Katherine Holmes, Beverley A Rothermel, Victoria A Simms, Victoria L Heath, Michael J Cross
Regulator of calcineurin 1 (RCAN1) is an endogenous inhibitor of the calcineurin pathway in cells. It is expressed as two isoforms in vertebrates: RCAN1.1 is constitutively expressed in most tissues, whereas transcription of RCAN1.4 is induced by several stimuli that activate the calcineurin-NFAT pathway. RCAN1.4 is highly upregulated in response to VEGF in human endothelial cells in contrast to RCAN1.1 and is essential for efficient endothelial cell migration and tubular morphogenesis. Here, we show that RCAN1...
August 2017: Angiogenesis
https://www.readbyqxmd.com/read/28064310/-differentially-expressed-genes-in-the-locus-associated-with-relative-kidney-weight-and-resting-blood-pressure-in-hypertensive-rats-of-the-isiah-strain
#14
O E Redina, S E Smolenskaya, L A Fedoseeva, A L Markel
The comparative full-genome sequencing of transcriptomes of the renal cortex and medulla from hypertensive ISIAH rats and normotensive WAG rats revealed the differential expression of genes in the locus of chromosome 11 associated to the traits of resting blood pressure and relative kidney weight. Six differentially expressed genes (Kcne1, Rcan1, Mx1, Mx2, Tmprss2, and RGD1559516) were identified in the renal cortex, and three genes (Rcan1, Mx2, and Tmprss2) were identified in the renal medulla. An analysis of the functions of these genes pointed at the Rcan1 gene as the most relevant candidate gene associated with both the traits of resting blood pressure and relative kidney weight in ISIAH rats...
November 2016: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28061453/the-regulator-of-calcineurin-1-rcan1-inhibits-nuclear-factor-kappab-signaling-pathway-and-suppresses-human-malignant-glioma-cells-growth
#15
Xin Chen, Yuanyuan Hu, Shuo Wang, Xiulian Sun
Nuclear factor-kappaB (NF-κB) has a vital role in cell survival and inhibition of NF-κB had proven to be an efficient therapeutic pathway for various cancers though little is known about the underlying mechanism. Previously we identified regulator of calcineurin 1 (RCAN1) as an endogenous inhibitor of NF-κB signaling pathway in lymphoma. In the present study, we have solid data to show that RCAN1 can inhibit the nuclear translocation of NF-κB protein then affect the activity of NF-κB signaling pathway in glioma cells...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28059787/neurons-derived-from-induced-pluripotent-stem-cells-of-patients-with-down-syndrome-reproduce-early-stages-of-alzheimer-s-disease-type-pathology-in-vitro
#16
Erdem B Dashinimaev, Alexander S Artyuhov, Alexey P Bolshakov, Ekaterina A Vorotelyak, Andrey V Vasiliev
People with Down syndrome (DS) are at high risk of developing pathology similar to Alzheimer's disease (AD). Modeling of this pathology in vitro may be useful for studying this phenomenon. In this study, we analyzed three different cultures of neural cells carrying trisomy of chromosome 21, which were generated by directed differentiation from induced pluripotent stem cells (iPS cells). We report here that in vitro generated DS neural cells have abnormal metabolism of amyloid-β (Aβ) manifested by increased secretion and accumulation of Aβ granules of Aβ42 pathological isoform with upregulated expression of the APP gene...
2017: Journal of Alzheimer's Disease: JAD
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
#17
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 are 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...
May 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27917924/rcans-regulate-the-convergent-roles-of-nfatc1-in-bone-homeostasis
#18
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
#19
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
#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...
January 2017: Molecular Psychiatry
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