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Introduction
Education
January 2011 - December 2013
October 2005 - September 2010
Publications
Publications (53)
The degradation process of the antigens specific to MHC-I presentation depends mainly on the proteasomal proteases in the cytosol. However, since many antigens are glycoproteins, including tumour antigens or viruses envelope proteins, their glycosylation status could also affect their processing and presentation. Here we investigate the processing...
Various pathologies result from disruptions to or stress of endoplasmic reticulum (ER) homeostasis, such as Parkinson’s disease and most neurodegenerative illnesses, diabetes, pulmonary fibrosis, viral infections and cancers. A critical process in maintaining ER homeostasis is the selection of misfolded proteins by the ER quality-control system (ER...
EDEM2 (Endoplasmic reticulum Degradation-Enhancing alpha-Mannosidase-like protein 2) is one of the key-proteins suggested to be involved in the selection and degradation of misfolded proteins from the endoplasmic reticulum. The datasets discussed in this article are related to experiments covering affinity proteomics, label-free quantitative proteo...
N-glycosylation is a key process for various biological functions like protein folding, maturation and sorting for the conventional secretory compartment, cell-cell communication and immune response. This is usually accomplished by a complex system of mannosidases in which those from class I have an outstanding role, commonly involved in the early...
The impact of the peptide amino acids side-chain modifications on the immunological recognition has been scarcely explored. We investigate here the effect of methionine oxidation on the antigenicity of the melanoma immunodominant peptide 369-YMDGTMSQV-377 (YMD). Using CD8+ T cell activation assays, we found that the antigenicity of the sulfoxide fo...
Melanoma is a form of skin cancer that can rapidly invade distant organs. A distinctive feature of melanomas is their pigmentation status, as melanin is present in most skin melanomas, whilst many metastatic tumors could become amelanotic. Besides the obvious malfunction of the key genes of the melanin pathway, the amelanotic tumors could bear a ch...
Targeted molecular imaging is a valuable tool in cancer diagnosis. The palette of manganese isotopes provides an excellent opportunity for multimodal imaging, given that it possesses a long-lived positron-emitting isotope...
Betulinic acid (BA) has been extensively studied in recent years mainly for its antiproliferative and antitumor effect in various types of cancers. Limited data are available regarding the pharmacokinetic profile of BA, particularly its metabolic transformation in vivo. In this study, we present the screening and structural investigations by ESI Or...
Traditionally fermented foods and beverages are still produced and consumed at a large scale in Romania. They are rich sources for novel lactic acid bacteria with functional properties and with potential application in food industry or health. Lactobacillus helveticus 34.9, isolated from a home-made fermented milk is able to inhibit the growth of o...
“Drug repositioning” is a modern strategy used to uncover new applications for out-of-date drugs. In this context, nalidixic acid, the first member of the quinolone class with limited use today, has been selected to obtain nine new metal complexes with lanthanide cations (La3+, Sm3+, Eu3+, Gd3+, Tb3+); the experimental data suggest that the quinolo...
In this study, we developed a high-resolution tandem mass spectrometry (HR MS) approach to assess presumed changes in gangliosidome of a human hippocampus affected by temporal lobe epilepsy (TLE) in comparison with a normal hippocampus. Gangliosides, membrane glycolipids, are particularly diverse and abundant in the human brain, and participate in...
BACKGROUND AND AIMS
Metabolic biomarkers are of high importance for the identification of early renal involvement in the course of type 2 diabetes mellitus (DM). Gangliosides, which are complex cell type-specific glycosphingolipids, consist of a sialylated oligosaccharide chain attached to a ceramide of different composition with respect to the sph...
Considering the valuable information provided by glycosphingolipids as molecular markers and the limited data available for their detection and characterization in patients suffering from Type 2 diabetic kidney disease (DKD), we developed and implemented a superior method based on high-resolution (HR) mass spectrometry (MS) and tandem MS (MS/MS) fo...
Tailoring extracellular vesicles (EVs) as targeted drug delivery systems to enhance the therapeutic efficacy showed superior advantage over liposomal therapies. Herein, we developed a novel nanotool for targeting B16.F10 murine melanoma, based on EVs stabilized with Polyethylene glycol (PEG) and loaded with doxorubicin (DOX). Small EVs were efficie...
We have developed here a superior methodology based on high-resolution mass spectrometry for screening and fragmentation analysis of gangliosides extracted and purified from the human motor cortex . The experiments, conducted on a nanoelectrospray Orbitrap mass spectroscope in the negative ion mode, allowed the discrimination in the native mixture...
Citation: Porosnicu, I.; Butnaru, C.M.; Tiseanu, I.; Stancu, E.; Munteanu, C.V.A.; Bita, B.I.; Duliu, O.G.; Sima, F. Y 2 O 3 Nanoparticles and X-ray Radiation-Induced Effects in Melanoma Cells. Molecules 2021, 26, 3403. https://doi. Abstract: The innovative strategy of using nanoparticles in radiotherapy has become an exciting topic due to the poss...
Tailoring extracellular vesicles (EVs) as targeted drug delivery systems to enhance the therapeutic efficacy showed superior advantage over liposomal therapies. Herein, we developed a novel nanotool for targeting B16.F10 murine melanoma, based on EVs stabilized with Polyethylene glycol (PEG) and loaded with doxorubicin (DOX). Nanosized EVs were eff...
EDEM3 recognizes and directs misfolded proteins to the ER-associated protein degradation (ERAD) process. EDEM3 was predicted to act as lectin or as a mannosidase because of its homology with the GH47 catalytic domain of the Man1B1, but the contribution of the other regions remained unresolved. Here, we dissect the molecular determinants governing E...
“Drug repositioning” is a current trend which proved useful in the search for new applications for existing, failed, no longer in use or abandoned drugs, particularly when addressing issues such as bacterial or cancer cells resistance to current therapeutic approaches. In this context, six new complexes of the first-generation quinolone oxolinic ac...
Aim: An advanced proteomics platform for protein biomarker discovery in diabetic chronic kidney disease (DKD) was developed, validated and implemented. Materials & methods: Three Type 2 diabetes mellitus patients and three control subjects were enrolled. Urinary peptides were extracted, samples were analyzed on a hybrid LTQ-Orbitrap Velos Pro instr...
In this study we have optimized nanoelectrospray ionization (nanoESI) high resolution mass spectrometry (HR MS) performed on Orbitrap instrument in the negative ion mode for the determination of the composition and structure of gangliosides extracted from human brain cavernous hemangioma.
The optimized HR MS platform, allowed the discrimination of...
Iba1 (ionized calcium binding adapter protein 1) is a cytoskeleton protein specific only for microglia and macrophages, where it acts as an actin-cross linking protein. Although frequently regarded as a marker of activation, its involvement in cell migration, membrane ruffling, phagocytosis or in microglia remodeling during immunological surveillan...
Endoplasmic reticulum (ER)-associated degradation (ERAD) is the main mechanism of targeting ER proteins for degradation to maintain homeostasis, and perturbations of ERAD lead to pathological conditions. ER-degradation enhancing α-mannosidase-like (EDEM1) was proposed to extract terminally misfolded proteins from the calnexin folding cycle and targ...
Since Graphene discovery, their associated derivate nanomaterials, Graphene Oxide (GO) and reduced-GO were in the forefront of continuous developments in bio-nano-technology due to unique physical-chemical properties. Although GO nano-colloids (GON) were proposed as drug release matrix for targeting cancer cells, there is still a concern regarding...
We have developed here a superior approach based on high resolution (HR) mass spectrometry (MS) for monitoring the changes occurring with development and aging in the composition and structure of cerebellar gangliosidome. The experiments were focused on the comparative screening and structural analysis of gangliosides expressed in fetal and aged ce...
Eyes absent (EYA) are non-thiol-based protein tyrosine phosphatases (PTPs) that also have transcriptional co-activator functions. Their PTP activity is involved in various pathologies. Recently, we demonstrated that Src tyrosine kinase phosphorylates human EYA3 by controlling its subcellular localization. We also found EYA3's ability to autodephosp...
Nucleosides with a norbornane fragment as sugar moiety (Figure 1) were found to have antiviral and anticancer activity [1]. [...]
Caudate nucleus (CN) is a specialized part of the dorsal striatum of each brain hemisphere involved in numerous cognitive processes. Caudate dysfunctions are associated with Alzheimer’s, Parkinson’s and Huntington’s disease, autism, and even schizophrenia. Most of the studies upon CN and related diseases were conducted using neuroimaging techniques...
Endoplasmic reticulum (ER) resident and secretory proteins that fail to reach their native conformation are selected for degradation through the ER-Associated Degradation (ERAD) pathway. The ER degradation-enhancing alpha-mannosidase-like proteins (EDEMs) were shown to be involved in this pathway but their precise role is still under investigation....
Widely dispersed throughout the entire body tissues, gangliosides (GGs) are essential components of neuronal cell membranes, where exhibit a vital role in neuronal function and brain development, directly influencing the neural tube formation, neurogenesis, neurotransmission, etc. Due to several factors, partial or complete closing faults of the fe...
Correction for ‘Secondary compounds in the catalytic hydrogenation of enone and allylic alcohol prostaglandin intermediates: isolation, characterization, and X-ray crystallography’ by Constantin I. Tănase et al. , New J. Chem. , 2019, DOI: 10.1039/c9nj01186b.
The discovery of the intraocular pressure reduction of 13,14-hydrogenated prostaglandins, from which Latanoprost is the most used drug in the glaucoma treatment, stimulated the researchers to improve its synthesis and that of structural analogues. We studied the hydrogenation of the 13,14-double bond of unsaturated allylic and ketone -lactone pros...
A long range tautomerism to a N,O-aminal by closing a tetrahydrofuran ring was put in evidence for an isoniazid analogue, whose accidental synthesis is presented in the paper. The isoniazid analogue was synthesized by the reaction of isoniazid with 2-hydroxy-tetrahydrofuran which was demonstrated to exist in old THF together with other peroxides, e...
Fatty acid amide analogues were synthesized from oleic acid, activated by 1,1'-carbonildiimidazole to oleoylimidazole and amines, and characterized by IR, MS, 1 Hand 13 C-NMR spectra. The compounds were investigated for their influence on body weight and food-intake effects on an obesity-induced mouse model.
Proteomics and imaging techniques are used more and more in tandem to investigate the virus-host interaction. Herein we present novel replicons, methods and trans-encapsidation systems suitable for determination of Hepatitis C Virus (HCV) proteins interactomes and live imaging of viral proteins dynamics in HCV cell culture (HCVcc) system. To identi...
The gangliosides (GGs) of the central nervous system (CNS) exhibit age and topographic specificity and these patterns may correlate with the functions and pathologies of the brain regions. Here, chloroform extraction, nanoelectrospray (nanoESI) negative ionization, together with Orbitrap high resolution mass spectrometry (MS) determined the topogra...
L-Dopachrometautomerase (L-DCT), also called Tyrosinase Related Protein-2 (TRP-2) is a melanoma antigen overexpressed in most chemo-/radio-therapeutical stress resistant tumor clones and Caveolin-1 (Cav1) is main regulator of numerous signaling processes. A structural and functional relationship between DCT and Cav1 is first presented here in two h...
Oleamide analogues were synthesized and fully characterized by IR, MS, 1H- And 13C-NMR spectra. Oleamide analogues were synthesized from oleic acid, activated by carbonyldiimidazole to oleoylimidazole, and amines. The compounds were investigated for their influence on bodyweight and food intake effects on mice. Two of the oleamide analogues are new...
Schindler disease is an inherited metabolic disorder caused by the deficient activity of α‐N ‐acetylgalactosaminidase enzyme. An accurate diagnosis requires, besides clinical examination, complex and costly biochemical and molecular genetic tests.
In the last years, mass spectrometry (MS) based on nanofluidics and high‐resolution instruments has be...
RATIONALE: Schindler disease is caused by the deficient activity of α-N-acetylgalactosaminidase, which leads to an abnormal accumulation of O-glycopeptides in tissues and body fluids. In this work the Schindler condition is for the first time approached by ion mobility (IMS) tandem mass spectrometry (MS/MS), for determining urine glycopeptide finge...
COMPARISON OF PROTEIN EXTRACTION CONDITIONS FOR EDEM3 INTERACTORS IN MELANOMA CELLS
CRISTIAN M. BUTNARU1, CRISTIAN V.A. MUNTEANU1, GABRIELA N. CHIRIȚOIU2, SIMONA GHENEA2, ANDREI J. PETRESCU1, ȘTEFANA M. PETRESCU2,*
1Departament of Bioinformatics and Structural Biochemistry
2Departament of Molecular Cell Biology, Institute of Biochemistry of the R...
Mass spectrometric investigations regarding phosphorylation of human EYA3 by SRC kinase
Iodo-, bromo-, chloro-etherification and oxymercuration–demercuration of hexahydropentalene 1,3-dimethanol were regioselectively realized with formation of pentalenofurane compounds in good yields. The corresponding hexahydropentaleno diacid and its monoester react regioselectively with MCPBA to give two γ-lactones. Haloetherification of the diacid...
The treatment of hexahydro-1.3-pentalenedimethanol 1 with MCPB acid gave a pentalenofurane compound 7 instead of an epoxide, in >90% yield by participation of the closer hydroxymethyl group in epoxidation. Acyl-protected derivatives 1a–1e gave a mixture of exo- and endo-epoxides 5/6 as expected, with exo-epoxides representing the major compound in...
Tyrosinase is a type 1 transmembrane protein, with a pivotal role in melanin synthesis within melanocytes. Tyrosinase is also upregulated in melanoma cells and for this reason it is used as a conventional biomarker in melanoma diagnostic. Moreover, many scientific reports present tyrosinase as a well-known autoantigen capable to elicit the immune s...
This paper presents the synthesis, physico-chemical characterization and preliminary pharmacological study of some oleamide analogues. Their synthesis was realized by basic amidation of methyl oleate with phenylalaninol and phenethylamine and by direct amidation of oleic acid with 1-naphthylamine and cyclohexylamine in the presence of 1, 1’ - carbo...
Phosphoketolases (PKs) are large thiamine pyrophosphate (TPP)-dependent enzymes playing key roles in a number of essential pathways of carbohydrate metabolism. The putative PK genes of Lactococcus lactis (Ll) and Leuconostoc mesenteroides (Lm) were cloned in a prokaryotic vector, and the encoded proteins were expressed and purified yielding high pu...
Human WDR1 (tryptophan-aspartate repeat containing protein 1) is a cytoplasmic protein involved in actin cytoskeleton regulation. It is the vertebrate homolog of yeast Aip1 and was first identified in chickens (1). WDR1 contains nine WD repeats of 30 to 40 amino acids, and these WD domains are recognized as domains which interact most in eukaryotes...
