scholarly journals Transient Receptor Potential Melastatin-8 Activation Induces Relaxation of Pulmonary Artery by Inhibition of Store-Operated Calcium Entry in Normoxic and Chronic Hypoxic Pulmonary Hypertensive Rats

2018 ◽  
Vol 365 (3) ◽  
pp. 544-555 ◽  
Author(s):  
Yun-Ping Mu ◽  
Da-Cen Lin ◽  
Si-Yi Zheng ◽  
Hai-Xia Jiao ◽  
James S. K. Sham ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Calcium Entry ◽  
Hypertensive Rats ◽  
Transient Receptor Potential Melastatin ◽  
Store Operated Calcium Entry ◽  
Transient Receptor

scholarly journals Up-Regulation of Transient Receptor Potential Canonical 1 (TRPC1) following Sarco(endo)plasmic Reticulum Ca2+ ATPase 2 Gene Silencing Promotes Cell Survival: A Potential Role for TRPC1 in Darier's Disease

2006 ◽  
Vol 17 (10) ◽  
pp. 4446-4458 ◽  
Author(s):  
Biswaranjan Pani ◽  
Eric Cornatzer ◽  
William Cornatzer ◽  
Dong-Min Shin ◽  
Mark R. Pittelkow ◽  
...  
Keyword(s):  
Cell Survival ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Calcium Entry ◽  
Hacat Cells ◽  
Transient Receptor Potential Canonical ◽  
Darier's Disease ◽  
Plasmic Reticulum ◽  
Store Operated Calcium Entry ◽  
Transient Receptor

The mechanism(s) involved in regulation of store operated calcium entry in Darier's disease (DD) is not known. We investigated the distribution and function of transient receptor potential canonical (TRPC) in epidermal skin cells. DD patients demonstrated up-regulation of TRPC1, but not TRPC3, in the squamous layers. Ca2+ influx was significantly higher in keratinocytes obtained from DD patients and showed enhanced proliferation compared with normal keratinocytes. Similar up-regulation of TRPC1 was also detected in epidermal layers of SERCA2+/− mice. HaCaT cells expressed TRPC1 in the plasma membrane. Expression of sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA)2 small interfering RNA (siRNA) in HaCaT cells increased TRPC1 levels and thapsigargin-stimulated Ca2+ influx, which was blocked by store-operated calcium entry inhibitors. Thapsigargin-stimulated intracellular Ca2+ release was decreased in DD cells. DD keratinocytes exhibited increased cell survival upon thapsigargin treatment. Alternatively, overexpression of TRPC1 or SERCA2-siRNA in HaCaT cells demonstrated resistance to thapsigargin-induced apoptosis. These effects were dependent on external Ca2+ and activation of nuclear factor-κB. Isotretinoin reduced Ca2+ entry in HaCaT cells and decreased survival of HaCaT and DD keratinocytes. These findings put forward a novel consequence of compromised SERCA2 function in DD wherein up-regulation of TRPC1 augments cell proliferation and restrict apoptosis. We suggest that the anti-apoptotic effect of TRPC1 could potentially contribute to abnormal keratosis in DD.

Differential regulation of transient receptor potential melastatin 6 and 7 cation channels by ANG II in vascular smooth muscle cells from spontaneously hypertensive rats

2006 ◽  
Vol 290 (1) ◽  
pp. R73-R78 ◽  
Author(s):  
Rhian M. Touyz ◽  
Ying He ◽  
Augusto C. I. Montezano ◽  
Guoying Yao ◽  
Vladimir Chubanov ◽  
...  
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Cation Channels ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Annexin 1 ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor

Intracellular Mg2+ depletion has been implicated in vascular dysfunction in hypertension. We demonstrated that transient receptor potential melastatin 7 (TRPM7) cation channels mediate Mg2+ influx in VSMCs. Whether this plays a role in [Mg2+]i deficiency in hypertension is unclear. Here, we tested the hypothesis that downregulation of TRPM7 and its homologue TRPM6 is associated with reduced [Mg2+]i and that ANG II negatively regulates TRPM6/7 in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR). Cultured VSMCs from Wistar Kyoto (WKY) and SHR were studied. mRNA and protein expression of TRPM6 and TRPM7 were assessed by RT-PCR and immunoblotting, respectively. Translocation of annexin-1, specific TRPM7 substrate, was measured as an index of TRPM7 activation. [Mg2+]i was determined using mag fura-2. VSMCs from WKY and SHR express TRPM6 and TRPM7. Basal TRPM6 expression was similar in WKY and SHR, but basal TRPM7 content was lower in VSMCs from SHR vs. WKY. This was associated with significantly reduced [Mg2+]i in SHR cells ( P < 0.01). ANG II time-dependently increased TRPM6 expression, with similar responses in WKY and SHR. ANG II significantly increased TRPM7 expression in WKY ( P < 0.05), but not in SHR. Annexin-1 translocation was reduced 1.5–2-fold in SHR vs. WKY. Our findings demonstrate that TRPM6 and TRPM7 are differentially regulated in VSMCs from SHR and WKY. Whereas TRPM6 is unaltered in SHR, expression of TRPM7 is blunted. This was associated with attenuated annexin-1 translocation and decreased VSMC [Mg2+]i in SHR. Downregulation of TRPM7, but not TRPM6, may play a role in altered Mg2+ homeostasis in VSMCs from SHR.

scholarly journals Noggin inhibits hypoxia-induced proliferation by targeting store-operated calcium entry and transient receptor potential cation channels

2015 ◽  
Vol 308 (11) ◽  
pp. C869-C878 ◽  
Author(s):  
Kai Yang ◽  
Wenju Lu ◽  
Jing Jia ◽  
Jie Zhang ◽  
Mingming Zhao ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Critical Role ◽  
Receptor Potential ◽  
Calcium Entry ◽  
Matrix Gla Protein ◽  
Cation Channels ◽  
Hypoxic Exposure ◽  
Store Operated Calcium Entry ◽  
Bmp4 Expression ◽  
Transient Receptor

Abnormally elevated bone morphogenetic protein 4 (BMP4) expression and mediated signaling play a critical role in the pathogenesis of chronic hypoxia-induced pulmonary hypertension (CHPH). In this study, we investigated the expression level and functional significance of four reported naturally occurring BMP4 antagonists, noggin, follistatin, gremlin1, and matrix gla protein (MGP), in the lung and distal pulmonary arterial smooth muscle cell (PASMC). A 21-day chronic hypoxic (10% O2) exposure rat model was utilized, which has been previously shown to successfully establish experimental CHPH. Among the four antagonists, noggin, but not the other three, was selectively downregulated by hypoxic exposure in both the lung tissue and PASMC, in correlation with markedly elevated BMP4 expression, suggesting that the loss of noggin might account for the hypoxia-triggered BMP4 signaling transduction. Then, by using treatment of extrogenous recombinant noggin protein, we further found that noggin significantly normalized 1) BMP4-induced phosphorylation of cellular p38 and ERK1/2; 2) BMP4-induced phosphorylation of cellular JAK2 and STAT3; 3) hypoxia-induced PASMC proliferation; 4) hypoxia-induced store-operated calcium entry (SOCE), and 5) hypoxia-increased expression of transient receptor potential cation channels (TRPC1 and TRPC6) in PASMC. In combination, these data strongly indicated that the hypoxia-suppressed noggin accounts, at least partially, for hypoxia-induced excessive PASMC proliferation, while restoration of noggin may be an effective way to inhibit cell proliferation by suppressing SOCE and TRPC expression.

scholarly journals The Antibody Receptor Fc Gamma Receptor IIIb Induces Calcium Entry via Transient Receptor Potential Melastatin 2 in Human Neutrophils

2021 ◽  
Vol 12 ◽  
Author(s):  
Omar Rafael Alemán ◽  
Nancy Mora ◽  
Carlos Rosales
Keyword(s):  
Actin Polymerization ◽  
Calcium Concentration ◽  
Transient Receptor Potential ◽  
Cytoplasmic Tail ◽  
Receptor Potential ◽  
Calcium Entry ◽  
Human Neutrophils ◽  
Cytoplasmic Calcium ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor

Human neutrophils express two unique antibody receptors for IgG, the FcγRIIa and the FcγRIIIb. FcγRIIa contains an immunoreceptor tyrosine-based activation motif (ITAM) sequence within its cytoplasmic tail, which is important for initiating signaling. In contrast, FcγRIIIb is a glycosylphosphatidylinositol (GPI)-linked receptor with no cytoplasmic tail. Although, the initial signaling mechanism for FcγRIIIb remains unknown, it is clear that both receptors are capable of initiating distinct neutrophil cellular functions. For example, FcγRIIa is known to induce an increase in L-selectin expression and efficient phagocytosis, while FcγRIIIb does not promote these responses. In contrast, FcγRIIIb has been reported to induce actin polymerization, activation of β1 integrins, and formation of neutrophils extracellular traps (NET) much more efficiently than FcγRIIa. Another function where these receptors seem to act differently is the increase of cytoplasmic calcium concentration. It has been known for a long time that FcγRIIa induces production of inositol triphosphate (IP3) to release calcium from intracellular stores, while FcγRIIIb does not use this phospholipid. Thus, the mechanism for FcγRIIIb-mediated calcium rise remains unknown. Transient Receptor Potential Melastatin 2 (TRPM2) is a calcium permeable channel expressed in many cell types including vascular smooth cells, endothelial cells and leukocytes. TRPM2 can be activated by protein kinase C (PKC) and by oxidative stress. Because we previously found that FcγRIIIb stimulation leading to NET formation involves PKC activation and reactive oxygen species (ROS) production, in this report we explored whether TRPM2 is activated via FcγRIIIb and mediates calcium rise in human neutrophils. Calcium rise was monitored after Fcγ receptors were stimulated by specific monoclonal antibodies in Fura-2-loaded neutrophils. The bacterial peptide fMLF and FcγRIIa induced a calcium rise coming initially from internal pools. In contrast, FcγRIIIb caused a calcium rise by inducing calcium entry from the extracellular medium. In addition, in the presence of 2-aminoethoxydiphenyl borate (2-APB) or of clotrimazole, two inhibitors of TRPM2, FcγRIIIb-induced calcium rise was blocked. fMLF- or FcγRIIa-induced calcium rise was not affected by these inhibitors. These data suggest for the first time that FcγRIIIb aggregation activates TRPM2, to induce an increase in cytoplasmic calcium concentration through calcium internalization in human neutrophils.

E3-targeted anti-TRPC5 antibody inhibits store-operated calcium entry in freshly isolated pial arterioles

2006 ◽  
Vol 291 (6) ◽  
pp. H2653-H2659 ◽  
Author(s):  
Shang-Zhong Xu ◽  
Guylain Boulay ◽  
Richard Flemming ◽  
David J. Beech
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Transient Receptor Potential ◽  
Ionic Current ◽  
Receptor Potential ◽  
Muscle Cells ◽  
Calcium Entry ◽  
Store Depletion ◽  
Store Operated Calcium Entry ◽  
Transient Receptor

Smooth muscle cells in arterioles have pivotal roles in the determination of blood pressure and distribution of local blood flow. The cells exhibit calcium entry in response to passive store depletion, but the mechanisms and relevance of this phenomenon are poorly understood. Previously, a role for canonical transient receptor potential 1 (TRPC1) was indicated, but heterologous expression studies showed TRPC1 to have poor function in isolation, suggesting a requirement for additional proteins. Here we test the hypothesis that TRPC5 is such an additional protein, because TRPC5 forms heteromultimeric channels with TRPC1, and RNA encoding TRPC5 is present in arterioles. Recordings were from arteriolar fragments freshly isolated from rabbit pial membrane. Ionic current in response to store depletion has properties like that of the TRPC1/TRPC5 heteromultimer, and so the effect of the E3-targeted, externally acting, anti-TRPC5 blocking antibody (T5E3) was explored. T5E3 suppressed calcium entry in store-depleted arterioles but had no effect in the absence of store depletion. T5E3 preadsorbed to its antigenic peptide did not inhibit calcium entry. TRPC6 is commonly detected in smooth muscle and is present in the arterioles, but T5E3 had no effect on TRPC6. The data suggest that calcium entry occurring in response to passive store depletion in smooth muscle cells of arterioles involves TRPC5 as well as TRPC1.

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