scholarly journals Phosphorylation of serine96 of histidine-rich calcium-binding protein by the Fam20C kinase functions to prevent cardiac arrhythmia

2017 ◽  
Vol 114 (34) ◽  
pp. 9098-9103 ◽  
Author(s):  
Adam J. Pollak ◽  
Kobra Haghighi ◽  
Swati Kunduri ◽  
Demetrios A. Arvanitis ◽  
Philip A. Bidwell ◽  
...  
Keyword(s):  
Calcium Binding ◽  
Secretory Pathway ◽  
Binding Protein ◽  
Sequence Similarity ◽  
Idiopathic Dilated Cardiomyopathy ◽  
Therapeutic Approaches ◽  
Storage Organelle ◽  
Life Threatening ◽  
Constitutive Phosphorylation

Precise Ca cycling through the sarcoplasmic reticulum (SR), a Ca storage organelle, is critical for proper cardiac muscle function. This cycling initially involves SR release of Ca via the ryanodine receptor, which is regulated by its interacting proteins junctin and triadin. The sarco/endoplasmic reticulum Ca ATPase (SERCA) pump then refills SR Ca stores. Histidine-rich Ca-binding protein (HRC) resides in the lumen of the SR, where it contributes to the regulation of Ca cycling by protecting stressed or failing hearts. The common Ser96Ala human genetic variant of HRC strongly correlates with life-threatening ventricular arrhythmias in patients with idiopathic dilated cardiomyopathy. However, the underlying molecular pathways of this disease remain undefined. Here, we demonstrate that family with sequence similarity 20C (Fam20C), a recently characterized protein kinase in the secretory pathway, phosphorylates HRC on Ser96. HRC Ser96 phosphorylation was confirmed in cells and human hearts. Furthermore, a Ser96Asp HRC variant, which mimics constitutive phosphorylation of Ser96, diminished delayed aftercontractions in HRC null cardiac myocytes. This HRC phosphomimetic variant was also able to rescue the aftercontractions elicited by the Ser96Ala variant, demonstrating that phosphorylation of Ser96 is critical for the cardioprotective function of HRC. Phosphorylation of HRC on Ser96 regulated the interactions of HRC with both triadin and SERCA2a, suggesting a unique mechanism for regulation of SR Ca homeostasis. This demonstration of the role of Fam20C-dependent phosphorylation in heart disease will open new avenues for potential therapeutic approaches against arrhythmias.

scholarly journals Calretinin expression in the mammalian neocortex: a review

2010 ◽  
pp. 665-677
Author(s):  
F Barinka ◽  
R Druga
Keyword(s):  
Calcium Binding ◽  
Binding Protein ◽  
Calcium Binding Protein ◽  
Actual Knowledge ◽  
Neuronal Homeostasis ◽  
Physiological Properties ◽  
Cortical Interneurons

In the mammalian neocortex, the calcium-binding protein calretinin is expressed in a subset of cortical interneurons. In the recent years, research on interneurons is one of the most rapidly growing fields in neuroscience. This review summarizes the actual knowledge of the functions of calretinin in neuronal homeostasis and particularly of the distribution, connectivity and physiological properties of calretinin expressing interneurons in the neocortex of rodents and primates, including humans. The possible neuroprotective role of calretinin and the presumed “resistance” of calretinin-expressing interneurons to various pathological processes are also discussed.

scholarly journals Calcium-binding protein of the chick chorioallantoic membrane. I. Immunohistochemical localization

1978 ◽  
Vol 77 (3) ◽  
pp. 743-751 ◽  
Author(s):  
RS Tuan ◽  
WA Scott ◽  
ZA Cohn
Keyword(s):  
Calcium Binding ◽  
Calcium Transport ◽  
External Surface ◽  
Binding Protein ◽  
Chorioallantoic Membrane ◽  
Immunohistochemical Localization ◽  
Calcium Binding Protein ◽  
Transport Function ◽  
Chick Chorioallantoic Membrane

The preparation of a specific antiserum (anti-CaBP) against the calcium-binding protein (CaBP) of the chorioallantoic membrane (CAM) is described. The anti-CaBP appeared to be specific for the CaBP by immunodiffusion and immunoelectrophoresis. Application of the anti-CaBP in immunofluorescence histochemistry revealed that the CaBP is present in the CAM only at developmental ages corresponding with the expression of the calcium transport function of the membrane. Furthermore, the CaBP is localized to the ectoderm of the CAM, appears to be exposed to the entire external surface of the ectoderm, and can be shown to be associated with cells enzymatically dissociated from the CAM. These results are consistent with a functional role of the CaBP in the CAM calcium transport process.

scholarly journals Role of the calcium-binding protein parvalbumin in short-term synaptic plasticity

2000 ◽  
Vol 97 (24) ◽  
pp. 13372-13377 ◽  
Author(s):  
O. Caillard ◽  
H. Moreno ◽  
B. Schwaller ◽  
I. Llano ◽  
M. R. Celio ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Calcium Binding ◽  
Binding Protein ◽  
Calcium Binding Protein ◽  
Short Term

scholarly journals Isolation and characterization of grancalcin, a novel 28 kDa EF-hand calcium-binding protein from human neutrophils

1992 ◽  
Vol 286 (2) ◽  
pp. 549-554 ◽  
Author(s):  
C G Teahan ◽  
N F Totty ◽  
A W Segal
Keyword(s):  
Sequence Analysis ◽  
Calcium Binding ◽  
Binding Protein ◽  
Sequence Similarity ◽  
Gel Filtration ◽  
Calcium Binding Protein ◽  
Peptide Sequence ◽  
Human Neutrophils ◽  
Isolation And Characterization ◽  
Ef Hand

A novel 28 kDa protein, which we have named ‘grancalcin’, has been identified in human neutrophils. The protein was isolated from the cytosol and found to be a homodimer, with an apparent molecular mass of 55 kDa on gel filtration. Polyclonal antibodies were raised to the native protein. N-Terminal sequence analysis and tryptic-peptide sequence analysis was performed. The protein exhibits sequence similarity to sorcin, a 24 kDa calcium-binding protein over-expressed in certain multi-drug-resistant cell lines. It appears to be a member of the EF-hand family of calcium-binding proteins. The association of a high proportion of this protein with the membranes and granules in the presence of physiological concentrations of calcium may indicate a role in granule-membrane fusion and degranulation.

scholarly journals Downregulation of S100 Calcium Binding Protein A12 inhibits the growth of glioma cells

2020 ◽  
Author(s):  
Chunhe Lu ◽  
Jia Liu ◽  
Mingze Yao ◽  
Lun Li ◽  
Guangyu Li
Keyword(s):  
Cell Apoptosis ◽  
Calcium Binding ◽  
Binding Protein ◽  
S100 Protein ◽  
Glioma Cells ◽  
Calcium Binding Protein ◽  
Migration And Invasion ◽  
S100 Calcium Binding Protein ◽  
Tumorigenesis And Progression

Abstract Introduction: S100 Calcium Binding Protein A12 (S100A12) is a member of the S100 protein family and is widely expressed in neutrophil and low expressed in lymphocytes and monocyte. However, the role of S100A12 in glioma has not yet been identified. Methods: In the present study, we carried out immunohistochemical investigation of S100A12 in 81 glioma tissues to determine the expression of s100A12 in glioma cells, and evaluate the clinical significance of S100A12 in glioma patients. Futher we knockdown the S100A12 by ShRNA, and evaluated cell proliferation, cell migration and cell apoptosis by MTT,clony formation assay, transwell assay ,flow cytometry assa and westernblot. Results: We found that S100A12 was upregulated in tissues of glioma patients and the expression was correlated to WHO stage and tumor size. Further, we found that knockdown S100A12 inhibits the proliferation, migration and invasion of glioma cells through regulating cell apoptosis and EMT. Conclusions: These findings demonstrated a novel function for S100A12 in glioma progression and suggested that S100A12 may be served as a new marker in the tumorigenesis and progression of glioma.

scholarly journals Downregulation of S100 Calcium Binding Protein A12 inhibits the growth of glioma cells

2020 ◽  
Author(s):  
Chunhe Lu ◽  
Jia Liu ◽  
Mingze Yao ◽  
Lun Li ◽  
Guangyu Li
Keyword(s):  
Cell Apoptosis ◽  
Calcium Binding ◽  
Binding Protein ◽  
S100 Protein ◽  
Glioma Cells ◽  
Calcium Binding Protein ◽  
Migration And Invasion ◽  
Transwell Assay ◽  
S100 Calcium Binding Protein

Abstract Background: S100 Calcium Binding Protein A12 (S100A12) is a member of the S100 protein family and is widely expressed in neutrophil and low expressed in lymphocytes and monocyte. However, the role of S100A12 in glioma has not yet been identified. Methods: In the present study, we carried out immunohistochemical investigation of S100A12 in 81 glioma tissues to determine the expression of s100A12 in glioma cells, and evaluate the clinical significance of S100A12 in glioma patients. Futher we knockdown the S100A12 by ShRNA, and evaluated cell proliferation, cell migration and cell apoptosis by MTT, clony formation assay, transwell assay ,flow cytometry assa and western blot. Results: We found that S100A12 was upregulated in tissues of glioma patients and the expression was correlated to WHO stage and tumor size. Further, we found that knockdown S100A12 inhibits the proliferation, migration and invasion of glioma cells through regulating cell apoptosis and EMT. Background: S100 Calcium Binding Protein A12 (S100A12) is a member of the S100 protein family and is widely expressed in neutrophil and low expressed in lymphocytes and monocyte. However, the role of S100A12 in glioma has not yet been identified. Methods: In the present study, we carried out immunohistochemical investigation of S100A12 in 81 glioma tissues to determine the expression of s100A12 in glioma cells, and evaluate the clinical significance of S100A12 in glioma patients. Futher we knockdown the S100A12 by ShRNA, and evaluated cell proliferation, cell migration and cell apoptosis by MTT, clony formation assay, transwell assay ,flow cytometry assa and western blot. Results: We found that S100A12 was upregulated in tissues of glioma patients and the expression was correlated to WHO stage and tumor size. Further, we found that knockdown S100A12 inhibits the proliferation, migration and invasion of glioma cells through regulating cell apoptosis and EMT.

scholarly journals Novel Therapeutic Approaches to Familial HLH (Emapalumab in FHL)

2020 ◽  
Vol 11 ◽  
Author(s):  
Pietro Merli ◽  
Mattia Algeri ◽  
Stefania Gaspari ◽  
Franco Locatelli
Keyword(s):  
Progressive Disease ◽  
Interferon Γ ◽  
Line Treatment ◽  
Therapeutic Approaches ◽  
Front Line ◽  
Hematopoietic Stem ◽  
Fda Approval ◽  
Neutralizing Monoclonal Antibody ◽  
Life Threatening

Primary Hemophagocytic lymphohistiocytosis (pHLH) is a rare, life-threatening, hyperinflammatory disorder, characterized by uncontrolled activation of the immune system. Mutations affecting several genes coding for proteins involved in the cytotoxicity machinery of both natural killer (NK) and T cells have been found to be responsible for the development of pHLH. So far, front-line treatment, established on the results of large international trials, is based on the use of glucocorticoids, etoposide ± cyclosporine, followed by allogeneic hematopoietic stem cell transplantation (HSCT), the sole curative treatment for the genetic forms of the disease. However, despite major efforts to improve the outcome of pHLH, many patients still experience unfavorable outcomes, as well as severe toxicities; moreover, treatment-refractory or relapsing disease is a major challenge for pediatricians/hematologists. In this article, we review the epidemiology, etiology and pathophysiology of pHLH, with a particular focus on different cytokines at the origin of the disease. The central role of interferon-γ (IFNγ) in the development and maintenance of hyperinflammation is analyzed. The value of emapalumab, a novel IFNγ-neutralizing monoclonal antibody is discussed. Available data support the use of emapalumab for treatment of pHLH patients with refractory, recurrent or progressive disease, or intolerance to conventional therapy, recently, leading to FDA approval of the drug for these indications. Additional data are needed to define the role of emapalumab in front-line treatment or in combination with other drugs.

Upregulation of S100 Calcium-Binding Protein A9 levels in the lungs of patients with idiopathic pulmonary fibrosis

2020 ◽  
Author(s):  
Jong-Uk Lee ◽  
Jong-Sook Park ◽  
Myung-Shin Kim ◽  
Jai-Seong Park ◽  
Eun-Suk Go ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Calcium Binding ◽  
Binding Protein ◽  
Survival Rates ◽  
Surrogate Marker ◽  
Calcium Binding Protein ◽  
S100 Calcium Binding Protein ◽  
Neutrophil Percentage

Abstract Background: Neutrophilic inflammation is a predominant characteristic of idiopathic pulmonary fibrosis (IPF). S100 Calcium-Binding Protein A9 (S100A9) is a neutrophil-derived protein and is involved in the development of neutrophil-related chronic inflammatory disorders. However, the role of S100A9 in IPF has not been evaluated.Methods : S100A9 concentrations were measured by ELISA in the BAL fluid obtained from NCs (n = 33) and patients with IPF (n = 87), NSIP (n = 22), HP (n = 19), or sarcoidosis (n = 10).Results: The S100A9 levels in BALF were significantly higher in patients with IPF than in those with NC (0.4 [0.18–0.9] vs. 0 [0–0.5] ng/mL, p < 0.001), HP (0.19 [0.07–0.33] ng/mL, p = 0.043), or sarcoidosis (0.06 [0–0.11] ng/mL, p < 0.001) patients. A S100A9 level of 0.093 ng/mL had discriminating powers of 78.79% for specificity and 81.61% for sensitivity between IPF patients and NCs. S100A9 levels were also correlated with neutrophil numbers (r = 0.356, p = 0.0007) and S100A9 was expressed on neutrophils and macrophages in the BALF of IPF patients. Patients with S100A9 levels above 0.5535 ng/mL or a neutrophil percentage above 49.09% (n = 43) had significantly lower survival rates than those with S100A9 levels at or below 0.5535 ng/mL and a neutrophil percentage at or below 49.09% (n = 41) (HR, 9.28; p = 0.0004).Conclusion: S100A9 may participate in the development and progression of IPF. The levels of S100A9 in BALF may be a surrogate marker for diagnosing IPF and predicting its prognosis.

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