Objective: The proliferation of predatory journals (PJs) poses challenges to the integrity and reliability of scientific research. This study provides a comprehensive overview of studies assessing predatory practices in the biomedical sciences and the evaluation of their methodologies.
Methods: We systematically searched three databases: PubMed, Web of Science and Scopus.
The determination of the cytotoxic potential of new and so far unknown compounds as well as their metabolites is fundamental in risk assessment. A variety of strategic endpoints have been defined to describe toxin-cell interactions, leading to prediction of cell fate. They involve measurement of metabolic endpoints, bio-energetic parameters or morphological cell modifications.
View Article and Find Full Text PDFOn the cellular level, oxidative stress may cause various responses, including autophagy and cell death. All of these outcomes involve disturbed Ca(2+) signaling. Here we show that the nuclear enzymes poly(ADP-ribose) polymerase 1 (PARP1) and PARP2 control cytosolic Ca(2+) shifts from extracellular and intracellular sources associated with autophagy or cell death.
View Article and Find Full Text PDFPoly(ADP-ribosyl)-ation is a nonprotein posttranslational modification of proteins and plays an integral part in cell physiology and pathology. The metabolism of poly(ADP-ribose) (PAR) is regulated by its synthesis by poly(ADP-ribose) polymerases (PARPs) and on the catabolic side by poly(ADP-ribose) glycohydrolase (PARG). PARPs convert NAD+ molecules into PAR chains that interact covalently or noncovalently with target proteins and thereby modify their structure and functions.
View Article and Find Full Text PDFCompared to most common posttranslational modifications of proteins, a peculiarity of poly(ADP-ribosyl)ation is the molecular heterogeneity and complexity of the reaction product, poly(ADP-ribose) (PAR). In fact, protein-bound PAR consists of variously sized (2-200 ADP-ribose residues) linear or branched molecules, negatively charged at physiological pH. It is now clear that PAR not only affects the function of the polypeptide to which it is covalently bound, but it can also influence the activity of other proteins by engaging specific noncovalent interactions.
View Article and Find Full Text PDFDNA damage to cells activates nuclear poly(ADP-ribose)polymerases (PARPs) and the poly(ADP-ribose) (PAR) synthesized is rapidly cleaved into ADP-ribose (ADPR) by PAR glycohydrolase (PARG) action. Naturally appearing tannin-like molecules have been implicated in specific inhibition of the PARG enzyme. This review deals with the in vitro and in vivo effects of tannins on PAR metabolism and their downstream actions in DNA damage signaling.
View Article and Find Full Text PDFOxidative DNA damage to cells activates poly(ADP-ribose)polymerase-1 (PARP-1) and the poly(ADP-ribose) formed is rapidly degraded to ADP-ribose by poly(ADP-ribose)glycohydrolase (PARG). Here we show that PARP-1 and PARG control extracellular Ca(2+) fluxes through melastatin-like transient receptor potential 2 channels (TRPM2) in a cell death signaling pathway. TRPM2 activation accounts for essentially the entire Ca(2+) influx into the cytosol, activating caspases and causing the translocation of apoptosis inducing factor (AIF) from the inner mitochondrial membrane to the nucleus followed by cell death.
View Article and Find Full Text PDFShelterin/telosome is a multi-protein complex at mammalian telomeres, anchored to the double-stranded region by the telomeric-repeat binding factors-1 and -2. In vitro modification of these proteins by poly(ADP-ribosyl)ation through poly(ADP-ribose) polymerases-5 (tankyrases) and -1/-2, respectively, impairs binding. Thereafter, at least telomeric-repeat binding factor-1 is degraded by the proteasome.
View Article and Find Full Text PDFCell Biol Toxicol
August 2009
Poly (ADP-ribose) polymerase-1 (PARP-1) is a DNA-binding enzyme involved in DNA damage processing, apoptosis, and genetic stability. Many lines of evidence suggest that PARP-1 is implicated in transcriptional regulation of various genes through the modulation of chromatin structure or through direct interaction with transcription factors and/or transcription factor-binding sites. In the present study, we applied TaqMan Low-Density Array analyses to investigate the expression of genes involved in apoptotic cell death induced by an alkylating agent.
View Article and Find Full Text PDFHuman DNA topoisomerase I plays a dual role in transcription, by controlling DNA supercoiling and by acting as a specific kinase for the SR-protein family of splicing factors. The two activities are mutually exclusive, but the identity of the molecular switch is unknown. Here we identify poly(ADP-ribose) as a physiological regulator of the two topoisomerase I functions.
View Article and Find Full Text PDFPAR [poly(ADP-ribose)] is a structural and regulatory component of multiprotein complexes in eukaryotic cells. PAR catabolism is accelerated under genotoxic stress conditions and this is largely attributable to the activity of a PARG (PAR glycohydrolase). To overcome the early embryonic lethality of parg-knockout mice and gain more insights into the biological functions of PARG, we used an RNA interference approach.
View Article and Find Full Text PDFDNA damage signaling is crucial for the maintenance of genome integrity. In higher eukaryotes a NAD+-dependent signal transduction mechanism has evolved to protect cells against the genome destabilizing effects of DNA strand breaks. The mechanism involves 2 nuclear enzymes that sense DNA strand breaks, poly(ADP-ribose) polymerase-1 and -2 (PARP-1 and PARP-2).
View Article and Find Full Text PDFThe formation of multiprotein complexes is l'ordre du jour in regulatory pathways. In this issue of Oncogene, Reale et al. report the formation of a particularly sophisticated complex of two important regulatory enzymes, DNMT1 (DNA methyltransferase-1) and PARP-1 (poly(ADP-ribose)polymerase-1).
View Article and Find Full Text PDFRegulating the topological state of DNA is a vital function of the enzyme DNA topoisomerase I. However, when acting on damaged DNA, topoisomerase I may get trapped in a covalent complex with nicked DNA (stalled topoisomerase I), that, if unrepaired, may lead to genomic instability or cell death. Here we show that ADP-ribose polymers target specific domains of topoisomerase I and reprogram the enzyme to remove itself from cleaved DNA and close the resulting gap.
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