How Arsenic, an Inorganic Pollutant, is Involved in the Physiology of Biomolecular Condensates in the Cell

The existence of membrane-less organelles in the cells has been known for a relatively long time. Of the membrane-less organelles, stress granules, processing bodies, and PML-NBs have been intensively investigated in relation to arsenic. The membrane-less organelles, which concentrate biomolecules (proteins, nucleic acids), have recently been shown to self-organize by means of phase separation/transition. These biomolecular condensates (membrane-less organelles) can provide local enhancement of the efficiency of specific reactions. The biomolecular condensates have attracted dramatic attention over the last decade because highly organized biochemical complexes in the cell have long been understood by the membrane-dependent compartmentalization. In this mini review, we highlight the initiation of phase separation for each biomolecular condensate in which arsenic could be involved. We further reflect on the adequacy of the arsenic-dependent ROS levels for the formation of biomolecular condensates. These perspectives led us to re-evaluate the biological action of arsenic from a biophysical and bio-rheological point of view

A New Technique for Improving Visualization of Mucosal Lesions During Endoscopic Photodynamic Therapy

A new device consisting of a conventional fiberscope and a new TV system (model OTV-S5, Olympus Optical Co., Tokyo, Japan) has been developed to achieve accurate irradiation of laser light in photodynamic therapy for gastric cancer. This model has high resolution and sensitivity, and its signal can be transmitted by red, green and blue. In front of the CCD we inserted a special interference filter which has specific absorption of red light with 2.3% transmissivity at a 630 nm wavelength and a 50 nm absorption band of full width at half maximum. The average transmittance in the visible region, except for at 630 nm, was 90%. A neutral density filter with 16% transmittance was added to adjust to the sensitivity of the CCD. The device makes it possible to perform accurate irradiation, because we can observe both the lesion and the laser spot on a monitor in original colors during irradiation

Application of thermoresponsive HPLC to forensic toxicology: determination of barbiturates in human urine

A high-performance liquid chromatography (HPLC) method has been developed for the assays of five barbiturates in human urine using a new thermoresponsive polymer separation column, which is composed of N-isopropylacrylamide polymer. According to elevating the column temperature from 10 ℃ to 50 ℃, five barbiturates, such as metharbital, primidone, phenobarbital, mephobarbital and pentobarbital, became well separated by this method. Five barbiturates showed good linearity in the range of 0.2-10 mg/ml. Good accuracy, precision and recoveries for these drugs were obtained at 1 and 5 μg/ml urine. The method with the new-type column seems to have high potential to be extensively used in forensic toxicology for analysis of many drugs and poisons by HPLC and HPLC-mass spectrometry (MS) (-MS)

Distribution and Excretion of Arsenic Metabolites after Oral Administration of Seafood-Related Organoarsenicals in Rats

Less information is available on the metabolism of organic arsenicals compared to inorganic arsenic in mammals. In the present study, we investigated tissue distribution, metabolism and excretion in rats of organoarsenicals, dimethylarsinic acid (DMAV), arsenobetaine (AB), arsenocholine (AC) and trimethylarsine oxide (TMAOV). Among these animals, arsenic concentrations in red blood cells (RBCs) and spleen increased remarkably only in the DMAV group. Hepatic arsenic concentration increased significantly only in the AC group. Approximately 17%, 72% and 60% of the dose was excreted in urine in two days in the DMAV, AB and AC groups, respectively; virtually the entire dose was excreted in urine in one day in the TMAOV group. On the other hand, approximately 18%, 0.2%, 0.5% and 0.1% of the dose was excreted in feces in two days in the DMAV, AB, AC and TMAOV groups, respectively. A large amount of arsenic was accumulated in RBCs in the form of protein-bound dimethylarsinous acid (DMAIII), and dimethylmonothioarsinic acid (DMMTAV), a reportedly toxic thio-arsenical, was found in urine and fecal extract in the DMAV group. These results suggest that intake of DMAV is a potential health hazard, given that the metabolites of DMAV, such as DMAIII and DMMTAV, are known to be highly toxic

Macrophage Receptor with Collagenous Structure (MARCO) Is Processed by either Macropinocytosis or Endocytosis-Autophagy Pathway

<div><p>The Macrophage Receptor with COllagenous structure (MARCO) protein is a plasma membrane receptor for un-opsonized or environmental particles on phagocytic cells. Here, we show that MARCO was internalized either by ruffling of plasma membrane followed by macropinocytosis or by endocytosis followed by fusion with autophagosome in CHO-K1 cells stably transfected with GFP-MARCO. The macropinocytic process generated large vesicles when the plasma membrane subsided. The endocytosis/autophagosome (amphisome) generated small fluorescent puncta which were visible in the presence of glutamine, chloroquine, bafilomycin, ammonia, and other amines. The small puncta, but not the large vesicles, co-localized with LC3B and lysosomes. The LC3-II/LC3-I ratio increased in the presence of glutamine, ammonia, and chloroquine in various cells. The small puncta trafficked between the peri-nuclear region and the distal ends of cells back and forth at rates of up to 2–3 μm/sec; tubulin, but not actin, regulated the trafficking of the small puncta. Besides phagocytosis MARCO, an adhesive plasma membrane receptor, may play a role in incorporation of various extracellular materials into the cell via both macropinocytic and endocytic pathways.</p></div

Stability of arsenic metabolites, arsenic triglutathione [As(GS)3] and methylarsenic diglutathione [CH3As(GS)2], in rat bile.

Inorganic arsenicals such as arsenite (iAs(III)) and arsenate (iAs(V)) are well-known human carcinogens. Arsenic is metabolized by repetitive reduction and oxidative methylation, and is excreted mainly in urine as monomethylated arsenicals (MMAs) and dimethylated arsenicals (DMAs). Recently, it has been shown that iAs(III) administered intravenously or orally is excreted into bile as arsenic-glutathione (As-GSH) complexes such as arsenic triglutathione [As(GS)(3)] and methylarsenic diglutathione [CH(3)As(GS)(2)]. In order to carry out the speciation of As-GSH complexes, it is important to understand their stability. The present study was designed to clarify the stability of As-GSH complexes in rat bile, and the role of GSH in stabilizing these complexes. Arsenic species were separated on an anion-exchange column and were analyzed by high-performance liquid chromatography-inductively coupled argon plasma mass spectrometry (HPLC-ICP MS). As(GS)(3) and CH(3)As(GS)(2) were unstable in bile and were hydrolyzed to iAs(III) and monomethylarsonous acid (MMA(III)) in the absence of GSH. As(GS)(3) appeared to be stable in the presence of 10mM GSH. Exogenously added GSH also stabilized CH(3)As(GS)(2) in bile at the concentrations of 5mM or higher. It has been suggested that trivalent arsenicals, especially MMA(III), are more toxic than corresponding pentavalent ones. These results suggest that GSH plays an important role in preventing hydrolysis of As-GSH complexes and the generation of well-known toxic trivalent arsenicals