Major vacuolar TPC1 channel in stress signaling: what matters, K, Ca conductance or an ion-flux independent mechanism?

Two-pore cation channel, TPC1, is ubiquitous in the vacuolar membrane of terrestrial plants and mediates the long distance signaling upon biotic and abiotic stresses. It possesses a wide pore, which transports small mono- and divalent cations. K is transported more than 10-fold faster than Ca, which binds with a higher affinity within the pore.

Reduction of Ca Entry by a Specific Block of KCa3.1 Channels Optimizes Cytotoxic Activity of NK Cells against T-ALL Jurkat Cells.

Degranulation mediated killing mechanism by NK cells is dependent on store-operated Ca entry (SOCE) and has optimum at moderate intracellular Ca elevations so that partial block of SOCE optimizes the killing process. In this study, we tested the effect of the selective blocker of KCa3.1 channel NS6180 on SOCE and the killing efficiency of NK cells from healthy donors and NK-92 cells against T-ALL cell line Jurkat.

In vitro simulation of the acute lymphoblastic leukemia niche: a critical view on the optimal approximation for drug testing.

Acute lymphoblastic leukemia with the worst prognosis is related to minimal residual disease. Minimal residual disease not only depends on the individual peculiarities of leukemic clones but also reflects the protective role of the acute lymphoblastic leukemia microenvironment. In this review, we discuss in detail cell-to-cell interactions in the 2 leukemic niches, more explored bone marrow and less studied extramedullary adipose tissue.

Dexamethasone-Induced Fatty Acid Oxidation and Autophagy/Mitophagy Are Essential for T-ALL Glucocorticoid Resistance.

ALL is a highly aggressive subtype of leukemia that affects children and adults. Glucocorticoids (GCs) are a critical component of the chemotherapeutic strategy against T-ALL. Cases of resistance to GC therapy and recurrent disease require novel strategies to overcome them.

Cannabidiol on the Path from the Lab to the Cancer Patient: Opportunities and Challenges.

Cannabidiol (CBD), a major non-psychotropic component of cannabis, is receiving growing attention as a potential anticancer agent. CBD suppresses the development of cancer in both in vitro (cancer cell culture) and in vivo (xenografts in immunodeficient mice) models. For critical evaluation of the advances of CBD on its path from laboratory research to practical application, in this review, we wish to call the attention of scientists and clinicians to the following issues: (a) the biological effects of CBD in cancer and healthy cells; (b) the anticancer effects of CBD in animal models and clinical case reports; (c) CBD's interaction with conventional anticancer drugs; (d) CBD's potential in palliative care for cancer patients; (e) CBD's tolerability and reported side effects; (f) CBD delivery for anticancer treatment.

Tamoxifen Sensitizes Acute Lymphoblastic Leukemia Cells to Cannabidiol by Targeting Cyclophilin-D and Altering Mitochondrial Ca Homeostasis.

Cytotoxic effects of cannabidiol (CBD) and tamoxifen (TAM) have been observed in several cancer types. We have recently shown that CBD primarily targets mitochondria, inducing a stable mitochondrial permeability transition pore (mPTP) and, consequently, the death of acute lymphoblastic leukemia (T-ALL) cells. Mitochondria have also been documented among cellular targets for the TAM action.

Overcoming Glucocorticoid Resistance in Acute Lymphoblastic Leukemia: Repurposed Drugs Can Improve the Protocol.

Glucocorticoids (GCs) are a central component of multi-drug treatment protocols against T and B acute lymphoblastic leukemia (ALL), which are used intensively during the remission induction to rapidly eliminate the leukemic blasts. The primary response to GCs predicts the overall response to treatment and clinical outcome. In this review, we have critically analyzed the available data on the effects of GCs on sensitive and resistant leukemic cells, in order to reveal the mechanisms of GC resistance and how these mechanisms may determine a poor outcome in ALL.

Modulation of Ion Transport Across Plant Membranes by Polyamines: Understanding Specific Modes of Action Under Stress.

This work critically discusses the direct and indirect effects of natural polyamines and their catabolites such as reactive oxygen species and γ-aminobutyric acid on the activity of key plant ion-transporting proteins such as plasma membrane H and Ca ATPases and K-selective and cation channels in the plasma membrane and tonoplast, in the context of their involvement in stress responses. Docking analysis predicts a distinct binding for putrescine and longer polyamines within the pore of the vacuolar TPC1/SV channel, one of the key determinants of the cell ionic homeostasis and signaling under stress conditions, and an additional site for spermine, which overlaps with the cytosolic regulatory Ca-binding site. Several unresolved problems are summarized, including the correct estimates of the subcellular levels of polyamines and their catabolites, their unexplored effects on nucleotide-gated and glutamate receptor channels of cell membranes and Ca-permeable and K-selective channels in the membranes of plant mitochondria and chloroplasts, and pleiotropic mechanisms of polyamines' action on H and Ca pumps.

Phenolic Compounds Cannabidiol, Curcumin and Quercetin Cause Mitochondrial Dysfunction and Suppress Acute Lymphoblastic Leukemia Cells.

Anticancer activity of different phenols is documented, but underlying mechanisms remain elusive. Recently, we have shown that cannabidiol kills the cells of acute lymphoblastic leukemia (ALL) by a direct interaction with mitochondria, with their consequent dysfunction. In the present study, cytotoxic effects of several phenolic compounds against human the T-ALL cell line Jurkat were tested by means of resazurin-based metabolic assay.

Kv1.3 Current Voltage Dependence in Lymphocytes is Modulated by Co-Culture with Bone Marrow-Derived Stromal Cells: B and T Cells Respond Differentially.

Background/aims: Kv1.3 channel is the only voltage-dependent potassium channel in plasma membrane of human lymphocytes. Bearing in mind a rather steep voltage-dependence of Kv1.

What is the role of putrescine accumulated under potassium deficiency?

Biomarker metabolites are of increasing interest in crops since they open avenues for precision agriculture, whereby nutritional needs and stresses can be monitored optimally. Putrescine has the potential to be a useful biomarker to reveal potassium (K ) deficiency. In fact, although this diamine has also been observed to increase during other stresses such as drought, cold or heavy metals, respective changes are comparably low.

Cannabidiol directly targets mitochondria and disturbs calcium homeostasis in acute lymphoblastic leukemia.

Anticancer properties of non-psychoactive cannabinoid cannabidiol (CBD) have been demonstrated on tumors of different histogenesis. Different molecular targets for CBD were proposed, including cannabinoid receptors and some plasma membrane ion channels. Here we have shown that cell lines derived from acute lymphoblastic leukemia of T lineage (T-ALL), but not resting healthy T cells, are highly sensitive to CBD treatment.

The energy cost of the tonoplast futile sodium leak.

Active removal of Na from the cytosol into the vacuole plays a critical role in salinity tissue tolerance, but another, often neglected component of this trait is Na retention in vacuoles. This retention is based on an efficient control of Na -permeable slow- and fast-vacuolar channels that mediate the back-leak of Na into cytosol and, if not regulated tightly, could result in a futile cycle. This Tansley insight summarizes our current knowledge of regulation of tonoplast Na -permeable channels and discusses the energy cost of vacuolar Na sequestration, under different scenarios.

Mitochondria as emerging targets for therapies against T cell acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) comprises a heterogeneous group of hematologic malignancies, arising from diverse genetic alterations in the early lymphocyte development. T-cell subtype of ALL (T-ALL) accounts for about 15% and 25% of ALL in children and adults, respectively. Being less frequent among ALL subtypes, T-ALL represents a high-risk factor for poor prognosis due to its aggressiveness and resistance to common antileukemic drugs.

Powering the plasma membrane Ca2+-ROS self-amplifying loop.

This article comments on: Makavitskaya M, Svistunenko D, Navaselsky I, . 2018. Novel roles of ascorbate in plants: induction of cytosolic Ca signals and efflux from cells via anion channels.

Calcium transport across plant membranes: mechanisms and functions.

Contents Summary 49 I. Introduction 49 II. Physiological and structural characteristics of plant Ca -permeable ion channels 50 III.

Differential Activity of Voltage- and Ca-Dependent Potassium Channels in Leukemic T Cell Lines: Jurkat Cells Represent an Exceptional Case.

Activation of resting T cells relies on sustained Ca influx across the plasma membrane, which in turn depends on the functional expression of potassium channels, whose activity repolarizes the membrane potential. Depending on the T-cells subset, upon activation the expression of Ca- or voltage-activated K channels, KCa or Kv, is up-regulated. In this study, by means of patch-clamp technique in the whole cell mode, we have studied in detail the characteristics of Kv and KCa currents in resting and activated human T cells, the only well explored human T-leukemic cell line Jurkat, and two additional human leukemic T cell lines, CEM and MOLT-3.

An Anion Conductance, the Essential Component of the Hydroxyl-Radical-Induced Ion Current in Plant Roots.

Oxidative stress signaling is essential for plant adaptation to hostile environments. Previous studies revealed the essentiality of hydroxyl radicals (HO•)-induced activation of massive K⁺ efflux and a smaller Ca influx as an important component of plant adaptation to a broad range of abiotic stresses. Such activation would modify membrane potential making it more negative.

Two-pore cation (TPC) channel: not a shorthanded one.

Two-pore cation (TPC) channels form functional dimers in membranes, delineating acidic intracellular compartments such as vacuoles in plants and lysosomes in animals. TPC1 is ubiquitously expressed in thousands of copies per vacuole in terrestrial plants, where it is known as slow vacuolar (SV) channel. An SV channel possesses high permeability for Na+, K+, Mg2+, and Ca2+, but requires high (tens of μM) cytosolic Ca2+ and non-physiological positive voltages for its full activation.

Methods Related to Polyamine Control of Cation Transport Across Plant Membranes.

Polyamines (PAs) are unique polycationic metabolites, which modulate plants' growth, development, and stress responses. As polycations, PAs interfere with cationic transport systems as ion channels and ionotropic pumps. Here, we describe the application of two techniques, MIFE to study the effects of PAs on cation fluxes in vivo and conventional patch-clamp to evaluate the PA blockage of ion currents in isolated plant vacuoles.

Natural variation in primary root growth and K retention in roots of habanero pepper (Capsicum chinense) under salt stress.

In this work, we analysed the natural variation in mechanisms for protection against salt stress in pepper varieties (Capsicum chinense Jacq. cv. Rex, Chichen-Itza and Naranja and Capsicum annuum L.

Cell-Type-Specific H+-ATPase Activity in Root Tissues Enables K+ Retention and Mediates Acclimation of Barley (Hordeum vulgare) to Salinity Stress.

While the importance of cell type specificity in plant adaptive responses is widely accepted, only a limited number of studies have addressed this issue at the functional level. We have combined electrophysiological, imaging, and biochemical techniques to reveal the physiological mechanisms conferring higher sensitivity of apical root cells to salinity in barley (Hordeum vulgare). We show that salinity application to the root apex arrests root growth in a highly tissue- and treatment-specific manner.

Cholinergic Machinery as Relevant Target in Acute Lymphoblastic T Leukemia.

Various types of non-neuronal cells, including tumors, are able to produce acetylcholine (ACh), which acts as an autocrine/paracrine growth factor. T lymphocytes represent a key component of the non-neuronal cholinergic system. T cells-derived ACh is involved in a stimulation of their activation and proliferation, and acts as a regulator of immune response.

Ion Channels in Native Chloroplast Membranes: Challenges and Potential for Direct Patch-Clamp Studies.

Photosynthesis without any doubt depends on the activity of the chloroplast ion channels. The thylakoid ion channels participate in the fine partitioning of the light-generated proton-motive force (p.m.

Transport Across Chloroplast Membranes: Optimizing Photosynthesis for Adverse Environmental Conditions.

Chloroplasts are central to solar light harvesting and photosynthesis. Optimal chloroplast functioning is vitally dependent on a very intensive traffic of metabolites and ions between the cytosol and stroma, and should be attuned for adverse environmental conditions. This is achieved by an orchestrated regulation of a variety of transport systems located at chloroplast membranes such as porines, solute channels, ion-specific cation and anion channels, and various primary and secondary active transport systems.