Investigations of the lysophospholipid composition of human neutrophils under different stimulation conditions by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Matrix-assisted laser desorption / ionization time-of-flight mass spectrometry (MALDI-TOF MS) is usually used for the analyses of proteins, carbohydrates and oligonucleotides. In spite of the number of advantages that MALDI-TOF MS exhibits for lipid analysis, this method has not often been applied in this field. In this paper we have extended our previous studies on the suitability of MALDI-TOF MS for the investigation of changes in the content of lipid-derived second messengers in organic extracts of human neutrophils. Qualitative differences in the lysophospholipid composition in organic extracts of the human neutrophils under different stimulation conditions could be easily observed by MALDI-TOF MS. Although there are still some methodological problems to be solved before this method can be routinely applied for the quantification of different lipid classes in complex biological mixtures (such as organic extracts of human neutrophils) it is shown here that MALDI-TOF MS possesses the capability to be used as a simple screening method for the investigation of the content of lipid-derived second messengers and of signalling pathways in cells

Interakcija kompleksa prelaznih metala sa fosfolipidima i enzimima uključenim u metabolizam fosfolipida

Although metal complexes are efficient anti-proliferative agents in solid tumors, there are numerous side effects of these drugs such as nephrotoxicity and tumor cell resistance that must be overcome by synthesis of new more effective complexes, or by alternative approaches to the drug administration. Therefore, new Pt(II), Pt(IV), Ru(III) or Au(III) complexes are of particular interest and several of them have already reached the level of clinical testing. In particular platinum(IV) and ruthenium(III) complexes containing aromatic ligands, such as bipyridine, appear to be suitable candidates for studying the basic features of interaction with biomolecules.1 The strategy which should enable selectivity of metallo-drugs involves the administration of a drug as a prodrug, which will be activated and exhibit the action specifically in the tumor tissue. Another approach is the development of specific carrier for a drug. The most common mechanisms of the activation of metallo-drugs in the tumor cells involve their aquation/hydrolysis, photoactivation, pH-dependent activation or activation by reduction.2 In the case of Pt(II) based drugs, the first step in the interaction with biomolecules is their hydrolysis, which occurs in the cytosol, due to the lower Cl- concentration. After that, the stepwise ligand replacement reaction may occur, leading to the formation of more or less stable complex with a biomolecule, i.e. platination of nucleic acid.U ovom izlaganju će biti dat pregled rezultata koji govore o interakciji lekova na bazi metalnih kompleksa sa fosfolipidima, osnovnim sastojcima ćelijskih membrana, kao i sa enzimima koji su uključeni u metabolizam fosfolipida i produkciju važnih signalnih molekula. Pokazano je da čak i najmanje modifikacije u lipofilnosti liganda koji je u sastavu kompleksa dovode do značajnih izmena u unosu metalnog kompleksa u ćeliju. Pored interakcije kompleksa prelaznih metala, uglavnom sa negativno naelektrisanim fosfolipidima, uticaj kompleksa na osobine membrane je takođe pokazan: prisustvo kompleksa u membrani menja njene osobine i povećava njenu permeabilnost. Pored inhibicije raznih enzima, kompleksi prelaznih metala inhibiraju i enzime koji su uključeni u metabolizam fosfolipida, kao što je fosfolipaza A2. Pored pregleda dobijenih rezultata, u toku izlaganje će se diskutovati o prirodi navedenih interakcija, kao i o mogućim fiziološkim efektima i uticaju na progresiju tumora.49th Meeting of the Serbian Chemical Society : Kragujevac, May 13-14, 2011