Complement Component C5a and Fungal Pathogen Induce Diverse Responses through Crosstalk between Transient Receptor Potential Channel (TRPs) Subtypes in Human Conjunctival Epithelial Cells.

The conjunctiva has immune-responsive properties to protect the eye from infections. Its innate immune system reacts against external pathogens, such as fungi. The complement factor C5a is an important contributor to the initial immune response.

Thermosensitive TRP Channels Are Functionally Expressed and Influence the Lipogenesis in Human Meibomian Gland Cells.

While the involvement of thermosensitive transient receptor potential channels (TRPs) in dry eye disease (DED) has been known for years, their expression in the meibomian gland (MG) has never been investigated. This study aims to show their expression and involvement in the lipogenesis of the MG, providing a possible new drug target in the treatment of DED. Our RT-PCR, Western blot and immunofluorescence analysis showed the expression of , , and in the MG at the gene and the protein level.

Joint CB1 and NGF Receptor Activation Suppresses TRPM8 Activation in Etoposide-Resistant Retinoblastoma Cells.

In childhood, retinoblastoma (RB) is the most common primary tumor in the eye. Long term therapeutic management with etoposide of this life-threatening condition may have diminishing effectiveness since RB cells can develop cytostatic resistance to this drug. To determine whether changes in receptor-mediated control of Ca signaling are associated with resistance development, fluorescence calcium imaging, semi-quantitative RT-qPCR analyses, and trypan blue dye exclusion staining patterns are compared in WERI-ETOR (etoposide-insensitive) and WERI-Rb1 (etoposide-sensitive) cells.

L-Carnitine Suppresses Transient Receptor Potential Vanilloid Type 1 Activation in Human Corneal Epithelial Cells.

Tear film hyperosmolarity induces dry eye syndrome (DES) through transient receptor potential vanilloid type 1 (TRPV1) activation. L-carnitine is a viable therapeutic agent since it protects against this hypertonicity-induced response. Here, we investigated whether L-carnitine inhibits TRPV1 activation by blocking heat- or capsaicin-induced increases in Ca influx or hyperosmotic stress-induced cell volume shrinkage in a human corneal epithelial cell line (HCE-T).

Angiotensin-(1-7) mediated calcium signalling by MAS.

The G protein-coupled receptor, MAS, is the receptor of the endogenous ligand, Angiotensin (Ang)-(1-7). It is a promising drug target since the Ang-(1-7)/MAS axis is protective in the cardiovascular system. Therefore, a characterization of MAS signalling is important for developing novel therapeutics for cardiovascular diseases.

Targeted esterase-induced dye (TED) loading supports direct calcium imaging in eukaryotic cell-free systems.

Calcium imaging is an important functional tool for analysing ion channels, transporters and pumps for drug screening in living cells. Depicted eukaryotic cell-free systems utilize microsomes, derived from the endoplasmic reticulum to incorporate the synthesized membrane proteins-like ion channels. Carboxylesterase is required to cleave the acetoxymethyl ester moiety of the chemical calcium indicators in order to ensure its immobility across the endoplasmic reticulum membrane.

Protein Profiling of WERI-RB1 and Etoposide-Resistant WERI-ETOR Reveals New Insights into Topoisomerase Inhibitor Resistance in Retinoblastoma.

Chemotherapy resistance is one of the reasons for eye loss in patients with retinoblastoma (RB). RB chemotherapy resistance has been studied in different cell culture models, such as WERI-RB1. In addition, chemotherapy-resistant RB subclones, such as the etoposide-resistant WERI-ETOR cell line have been established to improve the understanding of chemotherapy resistance in RB.

TRPV4 Stimulation Level Regulates Ca-Dependent Control of Human Corneal Endothelial Cell Viability and Survival.

The functional contribution of transient receptor potential vanilloid 4 (TRPV4) expression in maintaining human corneal endothelial cells (HCEC) homeostasis is unclear. Accordingly, we determined the effects of TRPV4 gene and protein overexpression on responses modulating the viability and survival of HCEC. Q-PCR, Western blot, FACS analyses and fluorescence single-cell calcium imaging confirmed TRPV4 gene and protein overexpression in lentivirally transduced 12V4 cells derived from their parent HCEC-12 line.

Effects of butyrate on ruminal Ca transport: evidence for the involvement of apically expressed TRPV3 and TRPV4 channels.

The ruminal epithelium absorbs large quantities of NH and Ca. A role for TRPV3 has emerged, but data on TRPV4 are lacking. Furthermore, short-chain fatty acids (SCFA) stimulate ruminal Ca and NH uptake in vivo and in vitro, but the pathway is unclear.

L-carnitine suppresses transient receptor potential vanilloid type 1 activity and myofibroblast transdifferentiation in human corneal keratocytes.

Corneal stromal wound healing is a well-balanced process promoted by overlapping phases including keratocyte proliferation, inflammatory-related events, and tissue remodeling. L-carnitine as a natural antioxidant has shown potential to reduce stromal fibrosis, yet the underlying pathway is still unknown. Since transient receptor potential vanilloid 1 (TRPV1) is a potential drug target for improving the outcome of inflammatory/fibrogenic wound healing, we investigated if L-carnitine can mediate inhibition of the fibrotic response through suppression of TRPV1 activation in human corneal keratocytes (HCK).

Ascorbate-induced oxidative stress mediates TRP channel activation and cytotoxicity in human etoposide-sensitive and -resistant retinoblastoma cells.

There are indications that pharmacological doses of ascorbate (Asc) used as an adjuvant improve the chemotherapeutic management of cancer. This favorable outcome stems from its cytotoxic effects due to prooxidative mechanisms. Since regulation of intracellular Ca levels contributes to the maintenance of cell viability, we hypothesized that one of the effects of Asc includes disrupting regulation of intracellular Ca homeostasis.

[Importance of Transient Receptor Potential Channels of the Ocular Surface: Insights and Outlook - from Laboratory Research to Clinical Practice].

Optimal vision requires an ocular surface with vital epithelial coverage and a stable tear film. A multitude of endogenous and external factors may alter this delicate balance. Studies over the last decade have established that Ca is an important factor in the control of ocular surface epithelial function and has led to the identification of critical components.

[Neurotrophic keratopathy : Principles, diagnostics and treatment].

Corneal nerves are responsible for the reception of pain, temperature, and touch and are an important component of homeostasis of the ocular surface. When the corneal innervation is reduced, degenerative changes can be manifested as neurotrophic keratopathy (NK). In a stage-dependent course, corneal epithelial alterations and ulcers may occur, even leading to perforation.

TRPM8 Activation via 3-Iodothyronamine Blunts VEGF-Induced Transactivation of TRPV1 in Human Uveal Melanoma Cells.

In human uveal melanoma (UM), tumor enlargement is associated with increases in aqueous humor vascular endothelial growth factor-A (VEGF-A) content that induce neovascularization. 3-Iodothyronamine (3-TAM), an endogenous thyroid hormone metabolite, activates TRP melastatin 8 (TRPM8), which blunts TRP vanilloid 1 (TRPV1) activation by capsaicin (CAP) in human corneal, conjunctival epithelial cells, and stromal cells. We compare here the effects of TRPM8 activation on VEGF-induced transactivation of TRPV1 in an UM cell line (92.

3-Iodothyronamine Activates a Set of Membrane Proteins in Murine Hypothalamic Cell Lines.

3-Iodothyronamine (3-TAM) is an endogenous thyroid hormone metabolite. The profound pharmacological effects of 3-TAM on energy metabolism and thermal homeostasis have raised interest to elucidate its signaling properties in tissues that pertain to metabolic regulation and thermogenesis. Previous studies identified G protein-coupled receptors (GPCRs) and transient receptor potential channels (TRPs) as targets of 3-TAM in different cell types.

An incretin-based tri-agonist promotes superior insulin secretion from murine pancreatic islets via PLC activation.

Recently, a unimolecular tri-agonist with activity at glucagon-like peptide 1 receptor (GLP-1R), glucose dependent insulinotropic receptor, and the glucagon receptor was reported to improve glycemic control in mice. Here, we defined the underlying molecular mechanisms of enhanced insulin secretion in murine pancreatic islets for a specific tri-agonist. The tri-agonist induced an increase in insulin secretion from murine islets compared to the respective mono-agonists.

3-Iodothyronamine, a Novel Endogenous Modulator of Transient Receptor Potential Melastatin 8?

The decarboxylated and deiodinated thyroid hormone (TH) derivative, 3-iodothyronamine (3-TAM), is suggested to be involved in energy metabolism and thermoregulation. G protein-coupled receptors (GPCRs) are known as the main targets for 3-TAM; however, transient receptor potential channels (TRPs) were also recently identified as new targets of 3-TAM. This article reviews the current knowledge of a putative novel role of 3-TAM in the modulation of TRPs.

Role of TRPV channels in regulating various pancreatic β-cell functions: Lessons from in vitro studies.

Pancreatic β-cell functions are regulated by a variety of endogenous and exogenous factors. Calcium is one of the most potent triggers of β-cell growth, insulin production and exocytosis. Recently, others and we showed that TRPV channels are expressed in insulin producing cell lines and/or primary β-cells.

3-Iodothyronamine Decreases Expression of Genes Involved in Iodide Metabolism in Mouse Thyroids and Inhibits Iodide Uptake in PCCL3 Thyrocytes.

Background: 3-Iodothyronamine (3-TAM) is an endogenous decarboxylated thyroid hormone (TH) metabolite. Pharmacological doses of 3-TAM decrease heart rate, body temperature, and metabolic rate in rodents-effects that are contrary to classic TH excess. Furthermore, a single dose of 3-TAM was shown to suppress the hypothalamic-pituitary-thyroid (HPT) axis in rats.

TRPV6 modulates proliferation of human pancreatic neuroendocrine BON-1 tumour cells.

Highly Ca(2+) permeable receptor potential channel vanilloid type 6 (TRPV6) modulates a variety of biological functions including calcium-dependent cell growth and apoptosis. So far, the role of TRPV6 in controlling growth of pancreatic neuroendocrine tumour (NET) cells is unknown. In the present study, we characterize the expression of TRPV6 in pancreatic BON-1 and QGP-1 NET cells.

Upregulation of Transient Receptor Potential Vanilloid Type-1 Channel Activity and Ca2+ Influx Dysfunction in Human Pterygial Cells.

Purpose: The heat-sensitive transient receptor potential vanilloid type-1 (TRPV1) channel (i.e., capsaicin [CAP] receptor) is upregulated in numerous cancers.

Ocular transient receptor potential channel function in health and disease.

Transient receptor potential (TRP) channels sense and transduce environmental stimuli into Ca(2+) transients that in turn induce responses essential for cell function and adaptation. These non-selective channels with variable Ca(2+) selectivity are grouped into seven different subfamilies containing 28 subtypes based on differences in amino acid sequence homology. Many of these subtypes are expressed in the eye on both neuronal and non-neuronal cells where they affect a host of stress-induced regulatory responses essential for normal vision maintenance.

3-Iodothyronamine increases transient receptor potential melastatin channel 8 (TRPM8) activity in immortalized human corneal epithelial cells.

3-Iodothyronamine (3T1AM) is an endogenous thyroid hormone metabolite that interacts with the human trace amine-associated receptor 1 (hTAAR1), a G-protein-coupled receptor, to induce numerous physiological responses including dose-dependent body temperature lowering in rodents. 3T1AM also directly activates cold-sensitive transient receptor potential melastatin 8 (TRPM8) channels in human conjunctival epithelial cells (HCjEC) at constant temperature as well as reducing rises in IL-6 release induced by transient receptor potential vanilloid 1 (TRPV1) activation by capsaicin (CAP). Here, we describe that 3T1AM-induced TRPM8 activation suppresses through crosstalk TRPV1 activation in immortalized human corneal epithelial cells (HCEC).