Über die Bindungsart der amidierten Reste derβ-Aminodicarbonsäuren in Eiweißstoffen

Summary Gliadin and chymotrypsinogen, respectively, were treated with alkaline sodium hypochlorite solution equivalent to the carbonamide groups present, and then hydrolysed by acid. The proteins treated with dilute alkaline solution have been assayed in control experiments for their content of N-terminal amino acids. The degradation products identified by paper chromatography seem to indicate that in chymotrypsinogen the amido groups of the amino dicarboxylic acids represent asparaginyl (Ia) and glutaminyl (Ib) residues. In gliadin, besides these residues, the presence of isoglutaminyl residues (IVb) also seems to be probable.     

The cytotoxicity of eosinophil cationic protein/ribonuclease 3 on eukaryotic cell lines takes place through its aggregation on the cell membrane

Human eosinophil cationic protein (ECP)/ ribonuclease 3 (RNase 3) is a protein secreted from the secondary granules of activated eosinophils. Specific properties of ECP contribute to its cytotoxic activities associated with defense mechanisms. In this work the ECP cytotoxic activity on eukaryotic cell lines is analyzed. The ECP effects begin with its binding and aggregation to the cell surface, altering the cell membrane permeability and modifying the cell ionic equilibrium. No internalization of the protein is observed. These signals induce cell-specific morphological and biochemical changes such as chromatin condensation, reversion of membrane asymmetry, reactive oxygen species production and activation of caspase-3-like activity and, eventually, cell death. However, the ribonuclease activity component of ECP is not involved in this process as no RNA degradation is observed. In summary, the cytotoxic effect of ECP is attained through a mechanism different from that of other cytotoxic RNases and may be related with the ECP accumulation associated with the inflammatory processes, in which eosinophils are present. Received 26 October 2007; accepted 23 November 2007     

Depression of experimental gastric ulcers and acute pancreatitis in rats treated by 5-azacytosine, 5-azacytidine and their N-methyl derivatives

5-Azacytosine, 1-methyl-5-azacytosine and 5-azacytidine administered to rats with a ligated pylorus block gastric secretion, gastric acidity, the extent of hemorrhage and the number and size of gastric defects. The same drugs also depress the development of experimental acute pancreatitis mediated in rats by interstitial administration of 7.5% natrium cholate into the pancreas in vivo. The drugs affected the amount of abdominal fluid and 6 h after the treatment the pathological changes were significantly decreased.     

Protein folding revisited. A polypeptide chain at the folding – misfolding – nonfolding cross-roads: which way to go?

The structure-function paradigm claims that a specific function of a protein is determined by its unique and rigid three-dimensional (3D) structure. Thus, following its biosynthesis on the ribosome, a protein must fold to be functional. This idea represents one of the cornerstones of modern biology. Numerous cases when, due to the effect of environmental factors or because of genetic defects (mutations), a polypeptide chain has lost its capability to gain a proper functional 3D structure (i.e. became misfolded), seem to confirm this concept. Consequences of such misfolding are well known and represent lost of function, aggregation, development of conformational disorders and cell death. However, the recent revelation of countless examples of intrinsically disordered proteins has cast doubt on the general validity of the structure-function paradigm and revealed an intriguing route of functional disorder. Thus, in a living cell, a polypeptide chain chooses between three potential fates – functional folding, potentially deadly misfolding and mysterious nonfolding. This choice is dictated by the peculiarities of amino acid sequence and/or by the pressure of environmental factors. The aim of the present review is to outline some interesting features of these three routes.Received 5 March 2003; received after revision 28 March 2003; accepted 31 March 2003