A5054773363- Amino Acid Enzymes and Metabolism
- Metabolism and Genetic Disorders
- Drug Transport and Resistance Mechanisms
- Polyamine Metabolism and Applications
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Neonatal Respiratory Health Research
- Nitric Oxide and Endothelin Effects
- Epigenetics and DNA Methylation
- Ion Transport and Channel Regulation
- Muscle metabolism and nutrition
- DNA and Nucleic Acid Chemistry
- COVID-19 Clinical Research Studies
- PI3K/AKT/mTOR signaling in cancer
- Cancer, Hypoxia, and Metabolism
- Celiac Disease Research and Management
- Phagocytosis and Immune Regulation
- Folate and B Vitamins Research
- Biopolymer Synthesis and Applications
- Protein Kinase Regulation and GTPase Signaling
- Receptor Mechanisms and Signaling
- Aldose Reductase and Taurine
- Neuroscience and Neuropharmacology Research
- Molecular Sensors and Ion Detection
- Mitochondrial Function and Pathology
University of Parma
2015-2024
University of Milan
2002
General Department of Preventive Medicine
2002
University of California, Santa Barbara
1992
University of Michigan
1981
The transport of neutral amino acids and their interactions for uptake have been studied in skin-derived diploid human fibroblasts cultured at confluency.Properly timed preincubations a medium defined composition requirements adopted to control size internal acid pools regulatory interferences affecting transport.L-Proline, L-alanine, L-leucine were used as natural substrates.Amino exchange with preaccumulated molecules measured under conditions approaching initial entry rates the absence...
The regulation of the transport neutral amino acids across cell membrane by adaptive mechanisms has been studied in cultured human fibroblasts. Among three systems (A, ASC, and L) individually discriminated, only Na+-dependent System A was subject to regulation, showing enhancement its activity when cells were incubated under conditions acid shortage (derepression phase) decrease exposed a medium supplied with Site A-reactive (repression phase). Starvation-induced derepression reversal...
Drug-eluting stents are widely used to prevent restenosis but associated with late endothelial damage. To understand the basis for this effect, we have studied consequences of a prolonged incubation rapamycin on viability and functions cells. Human umbilical vein or aorta cells were exposed in absence presence tumour necrosis factor α (TNFα). After 24 h-incubation, (100 nM) caused significant cell loss increase both apoptosis necrosis, as quantified by propidium iodide staining, caspase 3...
Using L-cysteate and tcysteinesulfinate as model substrates, we characterize here a transport system, both in cultured rat hepatocytes human skin fibroblasts, serving for the anions glutamate aspartate, but not dipolar species glutamic aspartic acids.This system appears to be accompanied by second, lower affinity anionic forms, which is also Na'-dependent; this applies at least glutamate.These systems show usual degree of preference L-over D-glutamate and, fibroblast,...
Here, we report the antiproliferative/cytotoxic properties of 8-hydroxyquinoline (8-HQ) derivatives on HeLa cells in presence transition metal ions (Cu2+, Fe3+, Co2+, Ni2+). Two series ligands were tested, arylvinylquinolinic L1–L8 and arylethylenequinolinic L9–L16, which can all interact with by virtue N,O donor set 8-HQ; however, only L9–L16 are flexible enough to bind a multidentate fashion, thus exploiting additional functions. L1–L16 tested for their cytotoxicity cancer cells, both...
A subset of human hepatocellular carcinomas (HCC) exhibit mutations β-catenin gene CTNNB1 and overexpress Glutamine synthetase (GS). The CTNNB1-mutated HCC cell line HepG2 is sensitive to glutamine starvation induced in vitro with the antileukemic drug Crisantaspase GS inhibitor methionine-L-sulfoximine (MSO). Immunodeficient mice subcutaneous xenografts lines HC-AFW1 were treated and/or MSO, tumour growth was monitored. At end treatment, weight histology assessed. Serum tissue amino acids...
SUMMARY Although morphological criteria for apoptosis are in general reliable, no systematic comparison of the techniques employed thus far has yet been performed. In this study, using confocal laser microscopy, we compared performance annexin V-FITC and calcein-AM early detection living adherent cells. Experiments were carried out on two distinct cell lines, PC 12 NIH3T3, endowed with different shape adhesion properties. The apoptotic process was followed a prolonged period same cells...
The transport of L-glutamic acid has been studied in skin-derived diploid human fibroblasts.Competition analysis the presence and absence Na+ mathematical discrimination by nonlinear regression indicated that enters cell at least three systems: 1) a high affinity Na+-dependent system which found to be identical previously described for anionic amino acids (Gazzola, G. C.,
Background. Emerging evidences suggest that in severe COVID-19, multi-organ failure is associated with a hyperinflammatory state (the so-called “cytokine storm”) combination the development of prothrombotic state. The central role endothelial dysfunction pathogenesis disease to date accepted, but precise mechanisms underlying coagulopathy remain unclear. Whether alterations vascular homeostasis directly depend upon SARS-CoV-2 infection cells or, rather, occur secondarily activation...
Clinical and experimental evidence point to a dysregulated immune response caused by SARS-CoV-2 as the primary mechanism of lung disease in COVID-19. However, pathogenic mechanisms underlying COVID-19-associated ARDS (Acute Respiratory Distress Syndrome) remain incompletely understood. This study aims explore inflammatory responses alveolar epithelial cells either spike S1 protein or mixture cytokines secreted S1-activated macrophages.The exposure A549 supernatants from spike-activated...
The activity of transport system A for neutral amino acids is adaptively stimulated upon acid starvation. In cultured human fibroblasts this treatment causes an increase in the expression ATA2 transporter gene. mRNA and stimulation are suppressed by substrates, but they unaffected other acids. Supplementation acid-starved cells with substrates a decrease both activity. These results suggest direct relationship between
The thioamido function of [CuCl2(1H)]Cl (2) (1 = 4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole), a cytotoxic copper complex, was converted into thioether moieties, leading to the synthesis [CuCl2(3)]2 (4) and [CuCl2(5)] (6) (3 6-methyl-3-pyridin-2-yl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine; 5 4-amino-5-ethylthio-3-(2-pyridyl)-1,2,4-triazole). These complexes were structurally characterized, their stability constants, along with biological activity, determined. 4 6 slightly...
Abstract Background In the recessive aminoaciduria Lysinuric Protein Intolerance (LPI), mutations of SLC7A7 /y+LAT1 impair system y + L transport activity for cationic amino acids. A severe complication LPI is a form Pulmonary Alveolar Proteinosis (PAP), in which alveolar spaces are filled with lipoproteinaceous material because impaired surfactant clearance by resident macrophages. The pathogenesis LPI-associated PAP remains still obscure. present study investigates first time expression...
Selected oncogenic mutations support unregulated growth enhancing glutamine availability but increasing the dependence of tumor cells on amino acid. Data from literature indicate that a subset HepatoCellular Carcinomas (HCC) is characterized by β-catenin and overexpression Glutamine Synthetase (GS). To assess if this phenotype may constitute an example addiction, we treated four human HCC lines with enzyme LAsparaginase (ASNase), glutaminolytic drug. ASNase had significant antiproliferative...
Abstract y+LAT1 (encoded by SLC7A7 ), together with y+LAT2 SLC7A6 is the alternative light subunits composing heterodimeric transport system y+L for cationic and neutral amino acids. mutations cause lysinuric protein intolerance (LPI), an inherited multisystem disease characterized low plasma levels of arginine lysine, protein‐rich food intolerance, failure to thrive, hepatosplenomegaly, osteoporosis, lung involvement, kidney failure, haematologic immunological disorders. The reason...
Amino acid starvation markedly stimulates the activity of system A, a widely distributed transport route for neutral amino acids. The involvement MAPK (mitogen-activated protein kinase) pathways in this adaptive increase was studied cultured human fibroblasts. In these cells, 3-fold stimulation A required 6-h acid-free incubation. However, rapid tyrosine phosphorylation ERK (extracellular regulated 1 and 2, JNK (Jun N-terminal 1, but not p38, observed after substitution complete medium with...
ABSTRACT l-arginine metabolism in myeloid cells plays a central role the processes of macrophage activation and regulation immune responses. In this study, we investigated arginine transport activity expression related transporter genes during differentiation monocytes to macrophages. We show here that induction THP-1 monocyte by PMA markedly increases SLC7A7 mRNA y+LAT1 protein consequently, system y+L-mediated transport. Conversely, y+ decreases as result reduction CAT1 expression. The...
Lysinuric protein intolerance (LPI) is a recessively inherited aminoaciduria caused by mutations of SLC7A7, the gene encoding y+LAT1 light chain system y+L for cationic amino acid transport. The pathogenesis LPI still unknown. In this study, we have utilized silencing approach in macrophages and airway epithelial cells to investigate whether complications affecting lung immune are directly ascribable lack SLC7A7 or, rather, mediated an abnormal accumulation arginine mutated cells. When...
Human umbilical vein endothelial cells transport arginine through two Na + -independent systems. System y L is insensitive to N-ethylmaleimide (NEM), inhibited byl-leucine in the presence of , and referable expression SLC7A6/y LAT2, SLC7A7/y LAT1, SLC3A2/4F2hc. SLC7A1/CAT1 SLC7A2/CAT2B. Tumor necrosis factor-α (TNF-α) bacterial lipopolysaccharide induce a transient stimulation influx efflux system . Increased SLC7A2/CAT2B detectable from 3 h treatment, while SLC7A1 at later times incubation....