scholarly journals Does Erythropoietin Regulate TRPC Channels in Red Blood Cells?

2017 ◽  
Vol 41 (3) ◽  
pp. 1219-1228 ◽  
Author(s):  
Jens Danielczok ◽  
Laura Hertz ◽  
Sandra Ruppenthal ◽  
Elisabeth Kaiser ◽  
Polina Petkova-Kirova ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Transient Receptor Potential ◽  
Ion Homeostasis ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Erythroid Cell ◽  
Trpc Channels ◽  
Potential Channels ◽  
Human Rbcs

Background: Cation channels play an essential role in red blood cells (RBCs) ion homeostasis. One set of ion channels are the transient receptor potential channels of canonical type (TRPC channels). The abundance of these channels in primary erythroblasts, erythroid cell lines and RBCs was associated with an increase in intracellular Ca2+ upon stimulation with Erythropoietin (Epo). In contrast two independent studies on Epo-treated patients revealed diminished basal Ca2+ concentration or reduced phosphatidylserine exposure to the outer membrane leaflet. Methods: To resolve the seemingly conflicting reports we challenged mature human and mouse RBCs of several genotypes with Epo and Prostaglandin E2 (PGE2) and recorded the intracellular Ca2+ content. Next Generation Sequencing was utilised to approach a molecular analysis of reticulocytes. Results/Conclusions: Our results allow concluding that Epo and PGE2 regulation of the Ca2+ homeostasis is distinctly different between murine and human RBCs and that changes in intracellular Ca2+ upon Epo treatment is a primary rather than a compensatory effect. In human RBCs, Epo itself has no effect on Ca2+ fluxes but inhibits the PGE2-induced Ca2+ entry. In murine mature RBCs functional evidence indicates TRPC4/C5 mediated Ca2+ entry activated by Epo whereas PGE2 leads to a TRPC independent Ca2+ entry.

scholarly journals Major contribution of the 3/6/7 class of TRPC channels to myocardial ischemia/reperfusion and cellular hypoxia/reoxygenation injuries

2017 ◽  
Vol 114 (23) ◽  
pp. E4582-E4591 ◽  
Author(s):  
Xiju He ◽  
Shoutian Li ◽  
Benju Liu ◽  
Sebastian Susperreguy ◽  
Karina Formoso ◽  
...  
Keyword(s):  
Calcium Release ◽  
Transient Receptor Potential ◽  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion ◽  
Receptor Potential ◽  
Permeability Transition ◽  
Transient Receptor Potential Channels ◽  
Trpc Channels ◽  
Potential Channels

The injury phase after myocardial infarcts occurs during reperfusion and is a consequence of calcium release from internal stores combined with calcium entry, leading to cell death by apoptopic and necrotic processes. The mechanism(s) by which calcium enters cells has(ve) not been identified. Here, we identify canonical transient receptor potential channels (TRPC) 3 and 6 as the cation channels through which most of the damaging calcium enters cells to trigger their death, and we describe mechanisms activated during the injury phase. Working in vitro with H9c2 cardiomyoblasts subjected to 9-h hypoxia followed by 6-h reoxygenation (H/R), and analyzing changes occurring in areas-at-risk (AARs) of murine hearts subjected to a 30-min ischemia followed by 24-h reperfusion (I/R) protocol, we found: (i) that blocking TRPC with SKF96365 significantly ameliorated damage induced by H/R, including development of the mitochondrial permeability transition and proapoptotic changes in Bcl2/BAX ratios; and (ii) that AAR tissues had increased TUNEL+ cells, augmented Bcl2/BAX ratios, and increased p(S240)NFATc3, p(S473)AKT, p(S9)GSK3β, and TRPC3 and -6 proteins, consistent with activation of a positive-feedback loop in which calcium entering through TRPCs activates calcineurin-mediated NFATc3-directed transcription of TRPC genes, leading to more Ca2+ entry. All these changes were markedly reduced in mice lacking TRPC3, -6, and -7. The changes caused by I/R in AAR tissues were matched by those seen after H/R in cardiomyoblasts in all aspects except for p-AKT and p-GSK3β, which were decreased after H/R in cardiomyoblasts instead of increased. TRPC should be promising targets for pharmacologic intervention after cardiac infarcts.

scholarly journals Dynamic NHERF interaction with TRPC4/5 proteins is required for channel gating by diacylglycerol

2016 ◽  
Vol 114 (1) ◽  
pp. E37-E46 ◽  
Author(s):  
Ursula Storch ◽  
Anna-Lena Forst ◽  
Franziska Pardatscher ◽  
Serap Erdogmus ◽  
Maximilian Philipp ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Activation Mechanism ◽  
Binding Motif ◽  
Trpc Channels ◽  
Channel Activity ◽  
C Terminus ◽  
Potential Channels ◽  
Transient Receptor

The activation mechanism of the classical transient receptor potential channels TRPC4 and -5 via the Gq/11 protein-phospholipase C (PLC) signaling pathway has remained elusive so far. In contrast to all other TRPC channels, the PLC product diacylglycerol (DAG) is not sufficient for channel activation, whereas TRPC4/5 channel activity is potentiated by phosphatidylinositol 4,5-bisphosphate (PIP2) depletion. As a characteristic structural feature, TRPC4/5 channels contain a C-terminal PDZ-binding motif allowing for binding of the scaffolding proteins Na+/H+ exchanger regulatory factor (NHERF) 1 and 2. PKC inhibition or the exchange of threonine for alanine in the C-terminal PDZ-binding motif conferred DAG sensitivity to the channel. Altogether, we present a DAG-mediated activation mechanism for TRPC4/5 channels tightly regulated by NHERF1/2 interaction. PIP2 depletion evokes a C-terminal conformational change of TRPC5 proteins leading to dynamic dissociation of NHERF1/2 from the C terminus of TRPC5 as a prerequisite for DAG sensitivity. We show that NHERF proteins are direct regulators of ion channel activity and that DAG sensitivity is a distinctive hallmark of TRPC channels.

scholarly journals Intractable Itch in Atopic Dermatitis: Causes and Treatments

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 229
Author(s):  
Yoshie Umehara ◽  
Chanisa Kiatsurayanon ◽  
Juan Valentin Trujillo-Paez ◽  
Panjit Chieosilapatham ◽  
Ge Peng ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Atopic Dermatitis ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Clinical Problem ◽  
Transient Receptor Potential Channels ◽  
Protease Activated Receptors ◽  
H1 Antihistamines ◽  
Potential Channels

Itch or pruritus is the hallmark of atopic dermatitis and is defined as an unpleasant sensation that evokes the desire to scratch. It is also believed that itch is a signal of danger from various environmental factors or physiological abnormalities. Because histamine is a well-known substance inducing itch, H1-antihistamines are the most frequently used drugs to treat pruritus. However, H1-antihistamines are not fully effective against intractable itch in patients with atopic dermatitis. Given that intractable itch is a clinical problem that markedly decreases quality of life, its treatment in atopic dermatitis is of high importance. Histamine-independent itch may be elicited by various pruritogens, including proteases, cytokines, neuropeptides, lipids, and opioids, and their cognate receptors, such as protease-activated receptors, cytokine receptors, Mas-related G protein-coupled receptors, opioid receptors, and transient receptor potential channels. In addition, cutaneous hyperinnervation is partly involved in itch sensitization in the periphery. It is believed that dry skin is a key feature of intractable itch in atopic dermatitis. Treatment of the underlying conditions that cause itch is necessary to improve the quality of life of patients with atopic dermatitis. This review describes current insights into the pathophysiology of itch and its treatment in atopic dermatitis.

scholarly journals Effects of Ginger and its Pungent Constituents on Transient Receptor Potential Channels

2017 ◽  
Vol 112 (3) ◽  
pp. 250a
Author(s):  
Young-Soo Kim ◽  
Chan Sik Hong ◽  
Sang Weon Lee ◽  
Joo Hyun Nam ◽  
Byung Joo Kim
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Potential Channels ◽  
Transient Receptor

scholarly journals Differential role of TRP channels in prostate cancer

2007 ◽  
Vol 35 (1) ◽  
pp. 133-135 ◽  
Author(s):  
N. Prevarskaya ◽  
M. Flourakis ◽  
G. Bidaux ◽  
S. Thebault ◽  
R. Skryma
Keyword(s):  
Prostate Cancer ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Clinical Problem ◽  
Tissue Growth ◽  
Transient Receptor Potential Channels ◽  
Potential Channels ◽  
Differentiation And Proliferation

A major clinical problem with PC (prostate cancer) is the cell's ability to survive and proliferate upon androgen withdrawal. Indeed, deregulated cell differentiation and proliferation, together with the suppression of apoptosis, provides the condition for abnormal tissue growth. Here, we examine the differential role of TRP (transient receptor potential) channels in the control of Ca2+ homoeostasis and growth of PC cells.

What Evolutionary Evidence Implies About the Identity of the Mechanoelectrical Couplers in Vascular Smooth Muscle Cells

Physiology ◽  
2021 ◽  
Vol 36 (5) ◽  
pp. 292-306
Author(s):  
Heather A. Drummond
Keyword(s):  
Transient Receptor Potential ◽  
Molecular Model ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Potential Channels ◽  
Transient Receptor ◽  
Paradigm Shifting ◽  
G Protein Coupled ◽  
Evolutionary Role

Loss of pressure-induced vasoconstriction increases susceptibility to renal and cerebral vascular injury. Favored paradigms underlying initiation of the response include transient receptor potential channels coupled to G protein-coupled receptors or integrins as transducers. Degenerin channels may also mediate the response. This review addresses the 1) evolutionary role of these molecules in mechanosensing, 2) limitations to identifying mechanosensitive molecules, and 3) paradigm shifting molecular model for a VSMC mechanosensor.

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