scholarly journals Insulin-like Growth Factor-1 Regulates the Mechanosensitivity of Chondrocytes by Modulating TRPV4

2020 ◽  
Author(s):  
Nicholas Trompeter ◽  
Joseph D. Gardinier ◽  
Victor DeBarros ◽  
Mary Boggs ◽  
Vimal Gangadharan ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Growth Factor ◽  
Intracellular Calcium ◽  
Mechanical Stimulation ◽  
Atp Release ◽  
Calcium Flux ◽  
Cell Stiffness ◽  
Hypotonic Swelling ◽  
Trpv4 Channel ◽  
Intracellular Calcium Flux

ABSTRACTBoth mechanical and IGF-1 stimulation are required for normal articular cartilage development and maintenance of the extracellular matrix. While much effort has been made to define the signaling pathways associated with these anabolic stimuli, we focused on how these pathways interact to regulate chondrocyte function. The Transient Receptor Potential Vanilloid 4 (TRPV4) channel is central to chondrocyte mechanotransduction and regulation of cartilage homeostasis. However, the mechanism by which TRPV4 is mechanically gated or regulated is not clear. In this study we propose that insulin-like growth factor 1 (IGF-1), which is important in regulating matrix production during mechanical load, modulates TRPV4 channel activity. Our studies indicate that IGF-1 reduces hypotonic-induced TRPV4 currents, and intracellular calcium flux by increasing stress fiber formation and apparent cell stiffness. Disruption of F-actin following IFG-1 treatment results in the return of the intracellular calcium response to hypotonic swelling. Furthermore, we highlight that IGF-1 suppresses TRPV4 mediated calcium flux through the MAP7 binding domain (aa. 798-809), where actin binds to the TRPV4 channel. IGF-1 treatment differentially influences the intracellular calcium flux of HEK 293 cells stably expressing either wild-type or mutant (P799L or G800D) TRPV4 during hypotonic challenge. A key down-stream response to mechanical stimulation of chondrocytes is ATP release. Data here indicate that activation of TRPV4 through hypotonic swelling induces ATP release, but this release is greatly reduced with IGF-1 treatment. Taken together this study indicates that IGF-1 modulates TRPV4 channel response to mechanical stimulation by increasing cell stiffness. As chondrocyte response to mechanical stimulation is greatly altered during OA progression, IGF-1 presents as a promising candidate for prevention and treatment of articular cartilage damage.

β-Endorphin modulates T-cell intracellular calcium flux and c-myc expression via a potassium channel

1990 ◽  
Vol 27 (2-3) ◽  
pp. 163-171 ◽  
Author(s):  
Christopher J. Hough ◽  
John I. Halperin ◽  
Denise L. Mazorow ◽  
Stephen L. Yeandle ◽  
David B. Millar
Keyword(s):  
T Cell ◽  
Potassium Channel ◽  
Intracellular Calcium ◽  
Calcium Flux ◽  
Intracellular Calcium Flux

Eupatilin inhibits T-cell activation by modulation of intracellular calcium flux and NF-κB and NF-AT activity

2009 ◽  
Vol 108 (1) ◽  
pp. 225-236 ◽  
Author(s):  
Young-Dae Kim ◽  
Suck-Chei Choi ◽  
Tae-Young Oh ◽  
Jang-Soo Chun ◽  
Chang-Duk Jun
Keyword(s):  
T Cell ◽  
Intracellular Calcium ◽  
T Cell Activation ◽  
Cell Activation ◽  
Calcium Flux ◽  
Intracellular Calcium Flux

Prostanglandin D2 modulates human neutrophil intracellular calcium flux and inhibits superoxide release via its ring carbonyl

Life Sciences ◽  
1990 ◽  
Vol 46 (11) ◽  
pp. 793-801 ◽  
Author(s):  
Cuthbert O. Simpkins ◽  
Denise L. Mazorow ◽  
Sione T. Alailima ◽  
Elin A. Tate ◽  
William Sweatt ◽  
...  
Keyword(s):  
Intracellular Calcium ◽  
Human Neutrophil ◽  
Calcium Flux ◽  
Superoxide Release ◽  
Intracellular Calcium Flux

scholarly journals ZAP-70 enhances IgM signaling independent of its kinase activity in chronic lymphocytic leukemia

Blood ◽  
2008 ◽  
Vol 111 (5) ◽  
pp. 2685-2692 ◽  
Author(s):  
Liguang Chen ◽  
Lang Huynh ◽  
John Apgar ◽  
Li Tang ◽  
Laura Rassenti ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Intracellular Calcium ◽  
Kinase Activity ◽  
Cell Receptor ◽  
Sh2 Domain ◽  
Lymphocytic Leukemia ◽  
Calcium Flux ◽  
Response To Treatment ◽  
Intracellular Calcium Flux

We transduced chronic lymphocytic leukemia (CLL) cells lacking ZAP-70 with vectors encoding ZAP-70 or various mutant forms of ZAP-70 and monitored the response of transduced CLL cells to treatment with F(ab)2 anti-IgM (anti-μ). CLL cells made to express ZAP-70, a kinase-defective ZAP-70 (ZAP-70-KA369), or a ZAP-70 unable to bind c-Cbl (ZAP-YF292) experienced greater intracellular calcium flux and had greater increases in the levels of phosphorylated p72Syk, B-cell linker protein (BLNK), and phospholipase C-γ, and greater activation of the Ig accessory molecule CD79b in response to treatment with anti-μ than did mock-transfected CLL cells lacking ZAP-70. Transfection of CLL cells with vectors encoding truncated forms of ZAP-70 revealed that the SH2 domain, but not the SH1 domain, was necessary to enhance intracellular calcium flux in response to treatment with anti-μ. We conclude that ZAP-70 most likely acts as an adapter protein that facilitates B-cell receptor (BCR) signaling in CLL cells independent of its tyrosine kinase activity or its ability to interact with c-Cbl.

scholarly journals Heat induces interleukin-6 in skeletal muscle cells via TRPV1/PKC/CREB pathways

2017 ◽  
Vol 122 (3) ◽  
pp. 683-694 ◽  
Author(s):  
Syotaro Obi ◽  
Toshiaki Nakajima ◽  
Takaaki Hasegawa ◽  
Hironobu Kikuchi ◽  
Gaku Oguri ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Intracellular Calcium ◽  
Interleukin 6 ◽  
Transient Receptor Potential ◽  
Signal Transduction Pathway ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Calcium Flux ◽  
Dependent Manner ◽  
Intracellular Calcium Flux

Interleukin-6 (IL-6) is released from skeletal muscle cells and induced by exercise, heat, catecholamine, glucose, lipopolysaccharide, reactive oxygen species, and inflammation. However, the mechanism that induces release of IL-6 from skeletal muscle cells remains unknown. Thermosensitive transient receptor potential (TRP) proteins such as TRPV1–4 play vital roles in cellular functions. In this study we hypothesized that TRPV1 senses heat, transmits a signal into the nucleus, and produces IL-6. The purpose of the present study is to investigate the underlying mechanisms whereby skeletal muscle cells sense and respond to heat. When mouse myoblast cells were exposed to 37–42°C for 2 h, mRNA expression of IL-6 increased in a temperature-dependent manner. Heat also increased IL-6 secretion in myoblast cells. A fura 2 fluorescence dual-wavelength excitation method showed that heat increased intracellular calcium flux in a temperature-dependent manner. Intracellular calcium flux and IL-6 mRNA expression were increased by the TRPV1 agonists capsaicin and N-arachidonoyldopamine and decreased by the TRPV1 antagonists AMG9810 and SB366791 and siRNA-mediated knockdown of TRPV1. TRPV2, 3, and 4 agonists did not change intracellular calcium flux. Western blotting with inhibitors demonstrated that heat increased phosphorylation levels of TRPV1, followed by PKC and cAMP response element-binding protein (CREB). PKC inhibitors, Gö6983 and staurosporine, CREB inhibitors, curcumin and naphthol AS-E, and knockdown of CREB suppressed the heat-induced increases in IL-6. These results indicate that heat increases IL-6 in skeletal muscle cells through the TRPV1, PKC, and CREB signal transduction pathway.NEW & NOTEWORTHY Heat increases the release of interleukin-6 (IL-6) from skeletal muscle cells. IL-6 has been shown to serve immune responses and metabolic functions in muscle. It can be anti-inflammatory as well as proinflammatory. However, the mechanism that induces release of IL-6 from skeletal muscle cells remains unknown. Here we show that heat increases IL-6 in skeletal muscle cells through the transient receptor potential vannilloid 1, PKC, and cAMP response element-binding protein signal transduction pathway.

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