TRPM7 activity drives human CD4 T-cell activation and differentiation in a magnesium dependent manner.

T lymphocyte activation is a crucial process in the regulation of innate and adaptive immune responses. The ion channel-kinase TRPM7 has previously been implicated in cellular Mg homeostasis, proliferation, and immune cell modulation. Here, we show that pharmacological and genetic silencing of TRPM7 leads to diminished human CD4 T-cell activation and proliferation following TCR mediated stimulation.

Transient Receptor Potential Melastatin 7 (TRPM7) Ion Channel Inhibitors: Preliminary SAR and Conformational Studies of Xenicane Diterpenoids from the Hawaiian Soft Coral .

Waixenicin A, a xenicane diterpene from the octocoral , is a selective, potent inhibitor of the TRPM7 ion channel. To study the structure-activity relationship (SAR) of waixenicin A, we isolated and assayed related diterpenes from . In addition to known waixenicins A () and B (), we purified six xenicane diterpenes, 7,8-epoxywaixenicins A () and B (), 12-deacetylwaixenicin A (), waixenicin E (), waixenicin F (), and 20-acetoxyxeniafaraunol B ().

Promoting Health Research among Underrepresented Students through the HUI SRC.

The Hawai'i Pacific University Undergraduate Infrastructure Student Research Center (HUI SRC) is focused on increasing participation of historically underrepresented populations, such as Native Hawaiians, other Pacific Islanders (NHPI), and Filipinos, in tomorrow's biomedical and health research workforce. This is achieved by promoting engagement and competency in entrepreneurial biomedical and health research among undergraduate students. The HUI SRC was modeled after the Morgan State University ASCEND SRC funded by the National Institute of General Medical Sciences.

STIM1 signals through NFAT1 independently of Orai1 and SOCE to regulate breast cancer cell migration.

Store-operated calcium entry (SOCE) contributes to several physiological and pathological conditions including transcription, secretion, immunodeficiencies, and cancer. SOCE has been shown to be important for breast cancer cell migration where knockdown of SOCE components (STIM1 or Orai1) decreases cancer metastasis. Here we show unexpectedly that complete knockout of STIM1 (STIM1-KO) using gene editing in metastatic MDA-MB-231 breast cancer cells results in faster migration and enhanced invasion capacity.

Drugs acting at TRPM7 channels inhibit seizure-like activity.

Transient receptor potential cation subfamily M7 (TRPM7) channels are ion channels permeable to divalent cations. They are abundantly expressed with particularly high expression in the brain. Previous studies have highlighted the importance of TRPM7 channels in brain diseases such as stroke and traumatic brain injury, yet evidence for a role in seizures and epilepsy is lacking.

Piericones A and B as Potent Antithrombotics: Nanomolar Noncompetitive Protein Disulfide Isomerase Inhibitors with an Unexpected Chemical Architecture.

Extracellular protein disulfide isomerase (PDI) is a promising target for thrombotic-related diseases. Four potent PDI inhibitors with unprecedented chemical architectures, piericones A-D (), were isolated from . Their structures were elucidated by spectroscopic data analysis, chemical methods, quantum C nuclear magnetic resonance DP4+ and electronic circular dichroism calculations, and single-crystal X-ray diffraction analysis.

Hypoxia-Induced Neurite Outgrowth Involves Regulation Through TRPM7.

Transient receptor potential melastatin 7 (TRPM7) is a ubiquitously expressed divalent cation channel that plays a key role in cell functions such as ion homeostasis, cell proliferation, survival, and cytoskeletal dynamics and mediates cells death in hypoxic and ischemic conditions. Previously, TRPM7 was found to play a role in the neurite outgrowth and maturation of primary hippocampal neurons. Either knockdown of TRPM7 with target-specific shRNA or blocking channel conductance by a specific blocker waixenicin A enhanced axonal outgrowth in the primary neuronal culture.

TRPM7 restrains plasmin activity and promotes transforming growth factor-β1 signaling in primary human lung fibroblasts.

Sustained exposure of the lung to various environmental or occupational toxins may eventually lead to pulmonary fibrosis, a devastating disease with no cure. Pulmonary fibrosis is characterized by excessive deposition of extracellular matrix (ECM) proteins such as fibronectin and collagens. The peptidase plasmin degrades the ECM, but protein levels of the plasmin activator inhibitor-1 (PAI-1) are increased in fibrotic lung tissue, thereby dampening plasmin activity.

Modulators of TRPM7 and its potential as a drug target for brain tumours.

TRPM7 is a non-selective divalent cation channel with an alpha-kinase domain. Corresponding with its broad expression, TRPM7 has a role in a wide range of cell functions, including proliferation, migration, and survival. Growing evidence shows that TRPM7 is also aberrantly expressed in various cancers, including brain cancers.

Assessment of plastic ingestion by pole-caught pelagic predatory fish from O'ahu, Hawai'i.

Although the frequency of occurrence of plastic ingestion in the large-sized dolphinfish and tunas taken by the Hawai'i longline fishery is very low (frequency of occurrence < 5% of sampled individuals), the ingestion of plastic in smaller-sized specimens caught with pole-and-line gear by commercial and recreational fishers has not been investigated.This study examined ingestion of >0.25 mm marine plastic debris (MPD) by four predatory fish species caught by commercial fishers around the Main Hawaiian Islands, and documented ingestion in three species: 85.

Upregulated ethanolamine phospholipid synthesis via selenoprotein I is required for effective metabolic reprogramming during T cell activation.

Objective: T cell activation triggers metabolic reprogramming to meet increased demands for energy and metabolites required for cellular proliferation. Ethanolamine phospholipid synthesis has emerged as a regulator of metabolic shifts in stem cells and cancer cells, which led us to investigate its potential role during T cell activation.

Methods: As selenoprotein I (SELENOI) is an enzyme participating in two metabolic pathways for the synthesis of phosphatidylethanolamine (PE) and plasmenyl PE, we generated SELENOI-deficient mouse models to determine loss-of-function effects on metabolic reprogramming during T cell activation.

Inhibition of TRPM7 with waixenicin A reduces glioblastoma cellular functions.

Glioblastoma (GBM) is the most common malignant primary brain tumour originating in the CNS. Median patient survival is <15 months with standard treatment which consists of surgery alongside radiation therapy and temozolomide chemotherapy. However, because of the aggressive nature of GBM, and the significant toxicity of these adjuvant therapies, long-term therapeutic effects are unsatisfactory.

Waixenicin A, a marine-derived TRPM7 inhibitor: a promising CNS drug lead.

Ion channels are the third largest class of targets for therapeutic drugs. The pharmacology of ion channels is an important research area for identifying new treatment options for human diseases. The past decade or so has seen increasing interest in an ion channel protein belonging to the transient receptor potential (TRP) family, namely the melastatin subfamily member 7 (TRPM7), as an emerging drug target.

TRPM7 Mediates Neuronal Cell Death Upstream of Calcium/Calmodulin-Dependent Protein Kinase II and Calcineurin Mechanism in Neonatal Hypoxic-Ischemic Brain Injury.

Transient receptor potential melastatin 7 (TRPM7), a calcium-permeable, ubiquitously expressed ion channel, is critical for axonal development, and mediates hypoxic and ischemic neuronal cell death in vitro and in vivo. However, the downstream mechanisms underlying the TRPM7-mediated processes in physiology and pathophysiology remain unclear. In this study, we employed a mouse model of hypoxic-ischemic brain cell death which mimics the pathophysiology of hypoxic-ischemic encephalopathy (HIE).

Divalent cation influx and calcium homeostasis in germinal vesicle mouse oocytes.

Prior to maturation, mouse oocytes are arrested at the germinal vesicle (GV) stage during which they experience constitutive calcium (Ca) influx and spontaneous Ca oscillations. The oscillations cease during maturation but Ca influx continues, as the oocytes' internal stores attain maximal content at the culmination of maturation, the metaphase II stage. The identity of the channel(s) that underlie this Ca influx has not been completely determined.

Isolation, Structure Determination, and Synthesis of Cyclic Tetraglutamic Acids from Box Jellyfish Species and .

Cubozoan nematocyst venoms contain known cytolytic and hemolytic proteins, but small molecule components have not been previously reported from cubozoan venom. We screened nematocyst extracts of and by LC-MS for the presence of small molecule metabolites. Three isomeric compounds, cnidarins 4A (), 4B (), and 4C (), were isolated from venom extracts and characterized by NMR and MS, which revealed their planar structure as cyclic γ-linked tetraglutamic acids.

TRPM7 channels play a role in high glucose-induced endoplasmic reticulum stress and neuronal cell apoptosis.

High-glucose (HG) levels and hyperglycemia associated with diabetes are known to cause neuronal damage. The detailed molecular mechanisms, however, remain to be elucidated. Here, we investigated the role of transient receptor potential melastatin 7 (TRPM7) channels in HG-mediated endoplasmic reticulum stress (ERS) and injury of NS20Y neuronal cells.

Validation of ATR FT-IR to identify polymers of plastic marine debris, including those ingested by marine organisms.

Polymer identification of plastic marine debris can help identify its sources, degradation, and fate. We optimized and validated a fast, simple, and accessible technique, attenuated total reflectance Fourier transform infrared spectroscopy (ATR FT-IR), to identify polymers contained in plastic ingested by sea turtles. Spectra of consumer good items with known resin identification codes #1-6 and several #7 plastics were compared to standard and raw manufactured polymers.

Scalaradial Is a Potent Inhibitor of Transient Receptor Potential Melastatin 2 (TRPM2) Ion Channels.

TRPM2 is a Ca-permeable, nonselective cation channel that plays a role in oxidant-induced cell death, insulin secretion, and cytokine release. Few TRPM2 inhibitors have been reported, which hampers the validation of TRPM2 as a drug target. While screening our in-house marine-derived chemical library, we identified scalaradial and 12-deacetylscalaradial as the active components within an extract of an undescribed species of Cacospongia (class Demospongiae, family Thorectidae) that strongly inhibited TRPM2-mediated Ca influx in TRPM2-overexpressing HEK293 cells.

Inhibition of TRPM7 suppresses cell proliferation of colon adenocarcinoma in vitro and induces hypomagnesemia in vivo without affecting azoxymethane-induced early colon cancer in mice.

Background: Magnesium (Mg) is an essential cation implicated in carcinogenesis, solid tumor progression and metastatic potential. The Transient Receptor Potential Melastatin Member 7 (TRPM7) is a divalent ion channel involved in cellular and systemic Mg homeostasis. Abnormal expression of TRPM7 is found in numerous cancers, including colon, implicating TRPM7 in this process.

The TRPM7 channel kinase regulates store-operated calcium entry.

Key Points: Pharmacological and molecular inhibition of transient receptor potential melastatin 7 (TRPM7) reduces store-operated calcium entry (SOCE). Overexpression of TRPM7 in TRPM7 cells restores SOCE. TRPM7 is not a store-operated calcium channel.

The coiled-coil domain of zebrafish TRPM7 regulates Mg·nucleotide sensitivity.

TRPM7 is a member of the Transient-Receptor-Potential Melastatin ion channel family. TRPM7 is a unique fusion protein of an ion channel and an α-kinase. Although mammalian TRPM7 is well characterized biophysically and its pivotal role in cancer, ischemia and cardiovascular disease is becoming increasingly evident, the study of TRPM7 in mouse models has been hampered by embryonic lethality of transgenic ablations.

Function and regulation of TRPM7, as well as intracellular magnesium content, are altered in cells expressing ΔF508-CFTR and G551D-CFTR.

Cystic fibrosis (CF), one of the most common fatal hereditary disorders, is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CFTR gene product is a multidomain adenosine triphosphate-binding cassette (ABC) protein that functions as a chloride (Cl(-)) channel that is regulated by intracellular magnesium [Mg(2+)]i. The most common mutations in CFTR are a deletion of a phenylalanine residue at position 508 (ΔF508-CFTR, 70-80 % of CF phenotypes) and a Gly551Asp substitution (G551D-CFTR, 4-5 % of alleles), which lead to decreased or almost abolished Cl(-) channel function, respectively.

Antimicrobial effects of marine algal extracts and cyanobacterial pure compounds against five foodborne pathogens.

The marine environment is a proven source of structurally complex and biologically active compounds. In this study, the antimicrobial effects of a small collection of marine-derived extracts and isolates, were evaluated against 5 foodborne pathogens using a broth dilution assay. Results demonstrated that algal extracts from Padina and Ulva species and cyanobacterial compounds antillatoxin B, laxaphycins A, B and B3, isomalyngamide A, and malyngamides C, I and J showed antimicrobial activity against Gram positive foodborne pathogens (Listeria monocytogenes, Bacillus cereus and Staphylococcus aureus) at low concentrations (⩽ 500 μg/ml).