Calcium Signaling Pathway

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Reecy, James M. - One of the best experts on this subject based on the ideXlab platform.

  • Gene co-expression analysis indicates potential Pathways and regulators of beef tenderness in Nellore cattle.
    Frontiers in Genetics v.9 n. 441 p. 1-18 2018., 2019
    Co-Authors: GonÇalves T. M., Koltes, James E., Regitano L. C. De A., Cesar A. S. M., Andrade S. C. Da S., Mourao G. B., Gasparin G., Moreira G. C. M., Fritz-waters E., Reecy, James M.
    Abstract:

    Beef tenderness, a complex trait affected by many factors, is economically important to beef quality, industry, and consumer?s palatability. In this study, RNA-Seq was used in network analysis to better understand the biological processes that lead to differences in beef tenderness. Skeletal muscle transcriptional profiles from 24 Nellore steers, selected by extreme estimated breeding values (EBVs) for shear force after 14 days of aging, were analyzed and 22 differentially expressed transcripts were identified. Among these were genes encoding ribosomal proteins, glutathione transporter ATP-binding cassette, sub-family C (CFTR/MRP), member 4 (ABCC4), and synaptotagmin IV (SYT4). Complementary co-expression analyses using Partial Correlation with Information Theory (PCIT), Phenotypic Impact Factor (PIF) and the Regulatory Impact Factor (RIF) methods identified candidate regulators and related Pathways. The PCIT analysis identified ubiquitin specific peptidase 2 (USP2), growth factor receptor-bound protein 10 (GBR10), anoctamin 1 (ANO1), and transmembrane BAX inhibitor motif containing 4 (TMBIM4) as the most differentially hubbed (DH) transcripts. The transcripts that had a significant correlation with USP2, GBR10, ANO1, and TMBIM4 enriched for proteasome KEGG Pathway. RIF analysis identified microRNAs as candidate regulators of variation in tenderness, including bta-mir-133a-2 and bta-mir-22. Both microRNAs have target genes present in the Calcium Signaling Pathway and apoptosis. PIF analysis identified myoglobin (MB), enolase 3 (ENO3), and carbonic anhydrase 3 (CA3) as potentially having fundamental roles in tenderness. Pathways identified in our study impacted in beef tenderness included: Calcium Signaling, apoptosis, and proteolysis. These findings underscore some of the complex molecular mechanisms that control beef tenderness in Nellore cattle.bitstream/item/193047/1/8-GeneCo-expressionAnalysis.pd

  • Gene Co-expression Analysis Indicates Potential Pathways and Regulators of Beef Tenderness in Nellore Cattle
    Iowa State University Digital Repository, 2018
    Co-Authors: Mangetti Tassia, De Almeida Regitano, Luciana Correia, Koltes, James E., Mello Cesar, Aline Silva, Da Silva Andrade, Sonia Cristina, Barreto Mourao Gerson, Gasparin Gustavo, Monteiro Moreira, Gabriel Costa, Fritz-waters Elyn, Reecy, James M.
    Abstract:

    Beef tenderness, a complex trait affected by many factors, is economically important to beef quality, industry, and consumer’s palatability. In this study, RNA-Seq was used in network analysis to better understand the biological processes that lead to differences in beef tenderness. Skeletal muscle transcriptional profiles from 24 Nellore steers, selected by extreme estimated breeding values (EBVs) for shear force after 14 days of aging, were analyzed and 22 differentially expressed transcripts were identified. Among these were genes encoding ribosomal proteins, glutathione transporter ATP-binding cassette, sub-family C (CFTR/MRP), member 4 (ABCC4), and synaptotagmin IV (SYT4). Complementary co-expression analyses using Partial Correlation with Information Theory (PCIT), Phenotypic Impact Factor (PIF) and the Regulatory Impact Factor (RIF) methods identified candidate regulators and related Pathways. The PCIT analysis identified ubiquitin specific peptidase 2 (USP2), growth factor receptor-bound protein 10 (GBR10), anoctamin 1 (ANO1), and transmembrane BAX inhibitor motif containing 4 (TMBIM4) as the most differentially hubbed (DH) transcripts. The transcripts that had a significant correlation with USP2, GBR10, ANO1, and TMBIM4 enriched for proteasome KEGG Pathway. RIF analysis identified microRNAs as candidate regulators of variation in tenderness, including bta-mir-133a-2and bta-mir-22. Both microRNAs have target genes present in the Calcium Signaling Pathway and apoptosis. PIF analysis identified myoglobin (MB), enolase 3 (ENO3), and carbonic anhydrase 3 (CA3) as potentially having fundamental roles in tenderness. Pathways identified in our study impacted in beef tenderness included: Calcium Signaling, apoptosis, and proteolysis. These findings underscore some of the complex molecular mechanisms that control beef tenderness in Nellore cattle

Jian Chen - One of the best experts on this subject based on the ideXlab platform.

  • migration and differentiation of osteoclast precursors under gradient fluid shear stress
    Biomechanics and Modeling in Mechanobiology, 2019
    Co-Authors: Taiyang Li, Chongyang Ye, Zebin Chen, Jian Chen
    Abstract:

    The skeleton can adapt to mechanical loading through bone remodeling, and osteoclasts close to microdamages are believed to initiate bone resorption. However, whether local mechanical loading, such as fluid flow, regulates recruitment and differentiation of osteoclast precursors at the site of bone resorption has yet to be investigated. In the present study, finite element analysis first revealed the existence of a low-fluid shear stress (FSS) field inside microdamage. Based on a custom-made device of cone-and-plate fluid chamber, finite element analysis and particle image velocimetry measurement were performed to verify the formation of gradient FSS flow field. Furthermore, the effects of gradient FSS on the migration, aggregation, and fusion of osteoclast precursors were observed. Osteoclast precursor RAW264.7 cells migrated along a radial direction toward the region with decreased FSS during exposure to gradient FSS stimulation for 40 min, thereby deviating from the direction of actual fluid flow indicated by fluorescent particles. When Calcium Signaling Pathway was inhibited by gadolinium and thapsigargin, cell migration toward a low-FSS region was significantly reduced. For the other cell lines MC3T3-E1, PDLF, rat mesenchymal stem cells, and Madin-Darby canine kidney epithelial cells, gradient FSS stimulation did not lead to low-FSS inclined migration. After being cultured under gradient FSS stimulation for 6 days, RAW264.7 cells showed significantly higher density and ratio of TRAP-positive multinucleated osteoclasts in the low-FSS region to those in the high-FSS region. Therefore, osteoclast precursor cells may exhibit the special ability to sense FSS gradient and tend to actively migrate toward low-FSS regions, which are regulated by Calcium Signaling Pathway.

  • migration and differentiation of osteoclast precursors under gradient fluid shear stress
    bioRxiv, 2018
    Co-Authors: Yan Gao, Qing Sun, Mengmeng Guo, Bin Ze Chen, Jian Chen, Bo Huo
    Abstract:

    The skeleton is able to adapt to mechanical loading through bone remodeling, i.e. bone resorption followed by bone formation. The osteoclasts close to microdamages are believed to initiate bone resorption, but whether local mechanical loading such as fluid flow regulates recruitment and differentiation of osteoclast precursors at the site of bone resorption has yet to be investigated. In the present study, finite element analysis first revealed that there exists low fluid shear stress (FSS) field inside microdamage. Basing on a custom-made device of cone-and-plate fluid chamber, finite element analysis and particle image velocimetry measurement were performed to verify the formation of gradient FSS flow field. Furthermore, the effects of gradient FSS on the migration, aggregation, and fusion of osteoclast precursors were observed. Results showed that osteoclast precursor RAW264.7 cells migrate along radial direction toward the region with lower FSS during exposure to gradient FSS stimulation for 40 min, obviously deviating from the direction of actual fluid flow indicated by fluorescent particles. When inhibiting Calcium Signaling Pathway with gadolinium and thapsigargin, cell migration toward low-FSS region was significantly reduced. For other cell lines, MC3T3-E1, PDLF, rMSC and MDCK, gradient FSS stimulation did not lead to the low-FSS-inclined migration. After being cultured under gradient FSS stimulation for 6 days, the density of RAW264.7 cells and the ratio of TRAP-positive multinucleated osteoclasts in low-FSS region were significantly higher than those in high-FSS region. Therefore, osteoclast precursor cells may have special ability to sense FSS gradient and tend to actively migrate toward low-FSS region, which is regulated by Calcium Signaling Pathway.

James E Hixson - One of the best experts on this subject based on the ideXlab platform.

Jeanpierre Kinet - One of the best experts on this subject based on the ideXlab platform.

  • phosphatidylinositol 3 4 5 trisphosphate ptdins 3 4 5 p3 tec kinase dependent Calcium Signaling Pathway a target for ship mediated inhibitory signals
    The EMBO Journal, 1998
    Co-Authors: Andrew M Scharenberg, Ousama Elhillal, David A Fruman, Laurie O Beitz, Siqi Lin, Ivan Gout, Lewis C Cantley, David J Rawlings, Jeanpierre Kinet
    Abstract:

    Tec family non-receptor tyrosine kinases have been implicated in signal transduction events initiated by cell surface receptors from a broad range of cell types, including an essential role in B-cell development. A unique feature of several Tec members among known tyrosine kinases is the presence of an N-terminal pleckstrin homology (PH) domain. We directly demonstrate that phosphatidylinositol-3,4,5-trisphosphate (PtdIns-3,4,5-P3) interacting with the PH domain acts as an upstream activation signal for Tec kinases, resulting in Tec kinase-dependent phospholipase Cgamma (PLCgamma) tyrosine phosphorylation and inositol trisphosphate production. In addition, we show that this Pathway is blocked when an SH2-containing inositol phosphatase (SHIP)-dependent inhibitory receptor is engaged. Together, our results suggest a general mechanism whereby PtdIns-3,4,5-P3 regulates receptor-dependent Calcium signals through the function of Tec kinases.

Dakai Xiao - One of the best experts on this subject based on the ideXlab platform.

  • z 3 4 5 4 trans tetramethoxystilbene a new analogue of resveratrol inhibits gefitinb resistant non small cell lung cancer via selectively elevating intracellular Calcium level
    Scientific Reports, 2015
    Co-Authors: Xingxing Fan, Xiaojun Yao, Vincent Kam Wai Wong, Jian Ding, Weiwei Xue, Tahira Mujtaba, Francesco Michelangeli, Min Huang, Jun Huang, Dakai Xiao
    Abstract:

    Calcium is a second messenger which is required for regulation of many cellular processes. However, excessive elevation or prolonged activation of Calcium Signaling would lead to cell death. As such, selectively regulating Calcium Signaling could be an alternative approach for anti-cancer therapy. Recently, we have identified an effective analogue of resveratrol, (Z)3,4,5,4′-trans-tetramethoxystilbene (TMS) which selectively elevated the intracellular Calcium level in gefitinib-resistant (G-R) non-small-cell lung cancer (NSCLC) cells. TMS exhibited significant inhibitory effect on G-R NSCLC cells, but not other NSCLC cells and normal lung epithelial cells. The phosphorylation and activation of EGFR were inhibited by TMS in G-R cells. TMS induced caspase-independent apoptosis and autophagy by directly binding to SERCA and causing endoplasmic reticulum (ER) stress and AMPK activation. Proteomics analysis also further confirmed that mTOR Pathway, which is the downstream of AMPK, was significantly suppressed by TMS. JNK, the cross-linker of ER stress and mTOR Pathway was significantly activated by TMS. In addition, the inhibition of JNK activation can partially block the effect of TMS. Taken together, TMS showed promising anti-cancer activity by mediating Calcium Signaling Pathway and inducing apoptosis as well as autophagy in G-R NSCLC cells, providing strategy in designing multi-targeting drug for treating G-R patients.