A5085109740- Endoplasmic Reticulum Stress and Disease
- Erythrocyte Function and Pathophysiology
- Thyroid Disorders and Treatments
- Cell death mechanisms and regulation
- Cellular transport and secretion
- Hemoglobin structure and function
- Ion channel regulation and function
- Glycosylation and Glycoproteins Research
- Protein Kinase Regulation and GTPase Signaling
- Pancreatic function and diabetes
- Adenosine and Purinergic Signaling
- NF-κB Signaling Pathways
- Heat shock proteins research
- Toxin Mechanisms and Immunotoxins
- Cholinesterase and Neurodegenerative Diseases
- Nicotinic Acetylcholine Receptors Study
- Neonatal Health and Biochemistry
- Cytokine Signaling Pathways and Interactions
- RNA Interference and Gene Delivery
- RNA and protein synthesis mechanisms
- RNA regulation and disease
- Protein Tyrosine Phosphatases
- Cancer Cells and Metastasis
- Genetics and Neurodevelopmental Disorders
- Immune Response and Inflammation
University of Salento
2009-2024
Istituto Nazionale di Fisica Nucleare, Sezione di Lecce
2000-2011
Innovation Engineering (Italy)
2002
Institute for Experimental Endocrinology and Oncology
1983-1999
University of Naples Federico II
1990-1995
University of Udine
1993-1994
Eunice Kennedy Shriver National Institute of Child Health and Human Development
1988
National Institutes of Health
1988
Conditions perturbing the homeostasis of endoplasmic reticulum (ER) cause accumulation unfolded proteins and trigger ER stress. In PC Cl3 thyroid cells, thapsigargin tunicamycin interfered with folding thyroglobulin, causing this very large secretory glycoprotein in ER. Consequently, mRNAs encoding BiP XBP-1 were induced spliced, respectively. absence apoptosis, differentiation cells was inhibited. mRNA protein levels thyroid-specific genes thyroperoxidase sodium/iodide symporter...
The present work was a comparative study of the bio-effects induced by exposure to 6 mT static magnetic field (MF) on several primary cultures and cell lines. Particular attention dedicated apoptosis. Cell viability, proliferation, intracellular Ca2+ concentration morphology were also examined. Primary human lymphocytes, mice thymocytes 3DO, U937, HeLa, HepG2 FRTL-5 cells grown in presence MF different apoptosis-inducing agents (cycloheximide, H2O2, puromycin, heat shock, etoposide)....
Iron regulation of the human transferrin receptor gene was examined in murine cells transformed with chimeric constructs containing gene's promoter and either structural for bacterial chloramphenicol acetyltransferase or cDNA. The activity heterologous indicator found to be approximately equal 3-fold higher treated iron chelator desferrioxamine than source, hemin. A degree seen expression cDNA driven by its own promoter. under control simian virus 40 early also iron-regulated. Several...
Nowadays, IBD-patient therapies are mainly based on corticosteroid, thiopurine, and immunomodulator treatments. Patients with active disease, that do not respond to corticosteroid and/or thiopurine treatment, can switch the usage of chimeric monoclonal antibody infliximab (IFX). However, date, no treatment appeared be conclusive in lowering incidence IBD relapses. With aim increase effectiveness IFX we combined it an adjuvant purple corn supplementation enriched anthocyanins. IBD-patients...
Thyroid hormonogenesis requires secretion of thyroglobulin, a protein comprising Cys-rich regions I, II, and III (referred to collectively as region I-II-III) followed by cholinesterase-like (ChEL) domain. Secretion mature thyroglobulin extensive folding glycosylation in the ER. Multiple reports have linked mutations ChEL domain congenital hypothyroidism humans rodents; these block from exiting ER induce stress. We report that, cell-based system, impaired I-II-III. Truncated devoid was...
CARMA proteins are scaffold molecules that contain a caspase recruitment domain and membrane-associated guanylate kinase-like domain. CARMA1 plays critical role in mediating activation of the NFkappaB transcription factor following antigen receptor stimulation both B T lymphocytes. However, biochemical mechanism by which regulates remains to be determined. Here we have shown CARMA3 physically associate with Ikappa kinase gamma/NFkappaB essential modulator (IkappaKgamma-NEMO) lymphoid...
We present the first identification of transient folding intermediates endogenous thyroglobulin (Tg; a large homodimeric secretory glycoprotein thyrocytes), which include mixed disulfides with oxidoreductases servicing Tg needs. Formation disulfide-linked adducts endoplasmic reticulum (ER) begins cotranslationally. Inhibition ER glucosidase activity blocked formation subgroup containing ERp57 while causing increased adduct protein disulfide isomerase (PDI), delayed resolution, perturbed...
Resin-based dental restorative materials release residual monomers that may affect the vitality of pulp cells. The purpose this study was to evaluate cytotoxic effect two light-cured with and without bis-GMA resin, respectively (Clearfil Majesty Posterior Clearfil Flow) a self-curing one DC Core Automix) when applied fibroblast cell line NIH-3T3. Samples were placed directly in contact cells for 24, 48, 72 96 h. Cytotoxicity evaluated by measuring death flow cytometry, proliferation curves...
The carboxyl-terminal cholinesterase-like (ChEL) domain of thyroglobulin (Tg) has been identified as critically important in Tg export from the endoplasmic reticulum. In a number human kindreds suffering congenital hypothyroidism, and cog goiter mouse rdw rat dwarf models, thyroid hormone synthesis is inhibited because mutations ChEL that block protein We hypothesize forms homodimers through noncovalent interactions involving two predicted alpha-helices each are homologous to dimerization...
Proteins containing the caspase recruiting domain (CARD) have emerged as critical regulators of different signal transduction pathways, including those controlling apoptosis and activation necrosis factor (NF)‐κB transcription factor. TUCAN/CARDINAL is a recently identified CARD‐containing protein involved in regulation caspases NF‐κB activation. We find that associates with DRAL, p53‐responsive gene implicated induction apoptosis. also show that, whereas exerts suppressive effect on...
The hormonal induction of thyroid peroxidase (TPO) mRNA is studied in the functional rat cell line FRTL-5 and compared to thyroglobulin (TG) I- uptake. TPO TG mRNAs are regulated by TSH insulin-like growth factor I (IGF-I) and/or insulin. However, while more sensitive regulation (5- 6-fold increase vs. 2- 3-fold IGF-I), IGF-I equally potent increasing levels (3- 4-fold). Regulation uptake appears be different: thus greatly (15-fold) increases uptake, or insulin completely ineffective....
Recent studies have indicated that endoplasmic reticulum stress, the unfolded protein response activation and altered GRP78 expression can play an important role in a variety of tumors development progression. Very recently we reported for first time is increased endometrial tumors. However, whether could growth and/or invasiveness cancer cells still unknown. Here report silencing affects both cell Ishikawa AN3CA cells, analyzed by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium...
During its initial folding in the endoplasmic reticulum (ER), newly synthesized thyroglobulin (Tg) is known to interact with calnexin and other ER molecular chaperones, but interaction calreticulin has not been examined previously. In present study, we have investigated interactions of endogenous Tg several chaperones. We find that, FRTL-5 PC-Cl3 cells, a carbohydrate-dependent manner, largely overlapping kinetics that are concomitant maturation intrachain disulphide bonds, preceding...
Maintaining a high Ca(2+) concentration in the lumen of endoplasmic reticulum (ER), by action sarco/endoplasmic Ca(2+)-ATPases (SERCAs), is important many cellular processes, such as Ca(2+)-mediated cytosolic signaling response to extracellular stimuli, cell growth and proliferation, synthesis, processing folding ER-translated proteins. In thyroid gland, SERCAs have not been studied yet, there little information available on general problems expression following neoplastic transformation....
Fragments of human genomic DNA corresponding to the promoter region gene for transferrin receptor have been cloned upstream bacterial chloramphenicol acetyltransferase and these constructs used assess activity following transfection into a rhabdomyosarcoma cell line. Progressive 5' deletions as well internal linker-substitution support critical role in expression sequence element approximately 70 bp mRNA start site. In this region, was found contain 11bp that are identical segment enhancers...
In vertebrates, the thyroglobulin (Tg) gene product must be exported to lumen of thyroid follicles for hormone synthesis. toto, Tg is composed multiple type-1 repeats connected by linker and hinge (altogether considered as "region I," nearly 1,200 residues); regions II-III (∼720 cholinesterase-like (ChEL) domain (∼570 residues). Regions ChEL rapidly acquire competence secretion, yet I-II-III require 20 min become a partially mature disulfide isomer; stabilization fully oxidized form requires...
Perturbing the endoplasmic reticulum homeostasis of thyroid cell lines with thapsigargin, a specific inhibitor sarco-endoplasmic Ca2+ adenosine triphosphatases, and tunicamycin, an N-linked glycosylation, blocked Tg in reticulum. This event was signaled outside resulted activation c-Jun N-terminal kinase (JNK)/stress-activated protein nuclear factor-κB (NF-κB) stress response pathways. Activation JNK/stress-activated signaling pathway assessed by measuring amount phospho-JNK activity JNK...
Thyroglobulin (Tg, precursor for thyroid hormone synthesis) is a large secreted glycoprotein composed of upstream regions I-II-III, followed by the approximately 570 residue cholinesterase-like (ChEL) domain. ChEL has two identified functions: 1) homodimerization, and 2) binding to I-II-III that facilitates oxidative maturation required intracellular protein transport. Like its homologs in acetylcholinesterase (AChE) family, possesses carboxyl-terminal alpha-helices. We find Tg-AChE chimera...