ABSTRACT
Microplastics (MPs) have become a prevalent environmental concern, exerting detrimental effects on marine and terrestrial ecosystems, as well as human health. Addressing this urgent issue necessitates the implementation of coordinated waste management policies and strategies. In this study, we present a comprehensive review focusing on key results and the underlying mechanisms associated with microplastics. We examine their sources and pathways, elucidate their ecological and human health impacts, and evaluate the current state of waste management policies. By drawing upon recent research and pertinent case studies, we propose a range of practical solutions, encompassing enhanced recycling and waste reduction measures, product redesign, and innovative technological interventions. Moreover, we emphasize the imperative for collaboration and cooperation across sectors and jurisdictions to effectively tackle this pressing environmental challenge. The findings of this study contribute to the broader understanding of microplastics and provide valuable insights for policymakers, researchers, and stakeholders alike.
Subject(s)
Waste Management , Water Pollutants, Chemical , Humans , Microplastics , Plastics , Environmental Monitoring , Ecosystem , Water Pollutants, Chemical/analysisABSTRACT
Besides thriving on altered glucose metabolism, cancer cells undergo glutaminolysis to meet their energy demands. As the first enzyme in catalyzing glutaminolysis, human kidney-type glutaminase isoform (KGA) is becoming an attractive target for small molecules such as BPTES [bis-2-(5 phenylacetamido-1, 2, 4-thiadiazol-2-yl) ethyl sulfide], although the regulatory mechanism of KGA remains unknown. On the basis of crystal structures, we reveal that BPTES binds to an allosteric pocket at the dimer interface of KGA, triggering a dramatic conformational change of the key loop (Glu312-Pro329) near the catalytic site and rendering it inactive. The binding mode of BPTES on the hydrophobic pocket explains its specificity to KGA. Interestingly, KGA activity in cells is stimulated by EGF, and KGA associates with all three kinase components of the Raf-1/Mek2/Erk signaling module. However, the enhanced activity is abrogated by kinase-dead, dominant negative mutants of Raf-1 (Raf-1-K375M) and Mek2 (Mek2-K101A), protein phosphatase PP2A, and Mek-inhibitor U0126, indicative of phosphorylation-dependent regulation. Furthermore, treating cells that coexpressed Mek2-K101A and KGA with suboptimal level of BPTES leads to synergistic inhibition on cell proliferation. Consequently, mutating the crucial hydrophobic residues at this key loop abrogates KGA activity and cell proliferation, despite the binding of constitutive active Mek2-S222/226D. These studies therefore offer insights into (i) allosteric inhibition of KGA by BPTES, revealing the dynamic nature of KGA's active and inhibitory sites, and (ii) cross-talk and regulation of KGA activities by EGF-mediated Raf-Mek-Erk signaling. These findings will help in the design of better inhibitors and strategies for the treatment of cancers addicted with glutamine metabolism.
Subject(s)
Glutaminase/metabolism , Kidney/enzymology , Models, Molecular , Protein Conformation , Signal Transduction/physiology , Sulfides/metabolism , Thiadiazoles/metabolism , Allosteric Regulation/physiology , Cell Line, Tumor , Cell Proliferation/drug effects , Crystallography , Glutaminase/chemistry , Humans , MAP Kinase Kinase 1/metabolism , MAP Kinase Kinase 2/genetics , MAP Kinase Signaling System/physiology , Mutation/genetics , Phosphorylation , Protein Binding , Proto-Oncogene Proteins c-raf/genetics , Proto-Oncogene Proteins c-raf/metabolism , Sulfides/pharmacology , Thiadiazoles/pharmacologyABSTRACT
A novel extraction procedure coupled with gas chromatography-mass spectrometric detection for quantification of organochlorine pesticides (OCPs) in water is described. Amphiphilic polyhydroxylated polyparaphenylene (PH-PPP) was synthesized and coated on the surfaces of a porous polypropylene hollow fiber membrane (HFM). Due to the high porosity of the HFM, maximum active surface area to achieve high extraction efficiency is expected. The polymer-coated HFM was used for the extraction of 15 OCPs from water. The extraction efficiency was compared with emerging and established methods such as liquid-phase microextraction (LPME), solid-phase microextraction (SPME) and stir bar sorptive extraction (SBSE) techniques. We term the current procedure as polymer-coated hollow fiber microextraction (PC-HFME). PC-HFME showed good selectivity and sensitivity. Detection limits for OCPs were in the range of 0.001-0.008 microg l(-1). The sensitivity and selectivity of the coated HFM could be adjusted by changing the characteristics of the coated PH-PPP film.
