Interplay between 20S proteasomes and prion proteins in scrapie disease.

Scrapie is a transmissible spongiform encephalopathy affecting the central nervous system in sheep. The key event in such neurodegeneration is the conversion of the normal prion protein (PrP(C)) into the pathological isoform (PrP(Sc)). Misfolded prion proteins are normally degraded by the proteasome.

Wheat sprout extract-induced apoptosis in human cancer cells by proteasomes modulation.

Natural occurring modulators of proteasome functionality are extensively investigated for their implication in cancer therapy. On the basis of our previous evidences both on proteasomal inhibition by monomeric polyphenols, and on the characterization of wheat sprout hydroalcoholic extract, herein we thoroughly report on a comparative study of the effect of wheat sprout extract on both normal and tumour cells. Treatment of isolated 20S proteasomes with wheat sprout extracts induced a gradual inhibition of all proteasome activities.

Co-chaperonin GroES as a modulator of proteasomal activity.

The proteasome has a crucial part in the degradation of normal, damaged, mutant or misfolded proteins within both the ubiquitin ATP-dependent and the ubiquitin ATP-independent pathways. Proteasome-mediated proteolysis is modulated by diverse factors, and in this regard, chaperonins have been attracting great interest. The investigation on the role of a co-chaperonin, namely GroES, in the modulation of proteasomal activity was the focus of this work.

Natural polyphenols as proteasome modulators and their role as anti-cancer compounds.

The purpose of this review is to discuss the effect of natural antioxidant compounds as modulators of the 20S proteasome, a multi-enzymatic multi-catalytic complex present in the cytoplasm and nucleus of eukaryotic cells and involved in several cellular activities such as cell-cycle progression, proliferation and the degradation of oxidized and damaged proteins. From this perspective, proteasome inhibition is a promising approach to anticancer therapy and such natural antioxidant effectors can be considered as potential relevant adjuvants and pharmacological models in the study of new drugs.

Amyloid peptides in different assembly states and related effects on isolated and cellular proteasomes.

The role of amyloid-beta protein (Abeta) in the pathogenesis of Alzheimer's disease (AD) has been widely investigated and amyloid aggregates are considered a major cause of neuronal dysfunction. Increasing evidence has identified a correlation between this protein and the proteasome, the cellular proteolytic machinery, in particular the ubiquitin-proteasome system. The 20S proteasome is the catalytic core of a complex, known as 26S proteasome, and is the main responsible for the clearance of misfolded and oxidized proteins.

Binding of aflatoxins to the 20S proteasome: effects on enzyme functionality and implications for oxidative stress and apoptosis.

Aflatoxins (AF) are contaminants of improperly stored foods; they are potent genotoxic and carcinogenic compounds, exerting their effects through damage to DNA. They can also induce mutations that increase oxidative damage. The goal of this study was to evaluate the possibility that a third mechanism could be involved in the carcinogenic action of aflatoxins, namely, direct binding to key enzymes involved in the regulatory pathways of the cell cycle, thereby modulating enzyme functionality.

Protein oxidation and cellular homeostasis: Emphasis on metabolism.

Reactive oxygen species (ROS) are generated as the result of a number of physiological and pathological processes. Once formed ROS can promote multiple forms of oxidative damage, including protein oxidation, and thereby influence the function of a diverse array of cellular processes. This review summarizes the mechanisms by which ROS are generated in a variety of cell types, outlines the mechanisms which control the levels of ROS, and describes specific proteins which are common targets of ROS.

Effect of polyphenolic compounds on the proteolytic activities of constitutive and immuno-proteasomes.

The effect of several polyphenols on the 20S proteasomes, both the constitutive and the LMP proteasomes, isolated from bovine tissues, has been investigated. Polyphenolic compounds show many biological activities such as antiviral, antibacterial, antifungal, anti-inflammatory, antimutagenic, and antiallergic activities. However, the molecular mechanism underlying these effects has not been identified.

Binding of recombinant PrPc to human plasminogen: kinetic and thermodynamic study using a resonant mirror biosensor.

Transmissible spongiform encephalopathies are a class of sporadic, genetic and transmissible neurodegenerative diseases that affect both humans and animals. Propagation of these diseases is thought to be due to the misfolding of a neuronal glyco-protein, PrP(c), into a pathological insoluble conformer, PrP(Sc). In earlier works, some serum components were identified as exclusive PrP(Sc)-interacting proteins (Fisher et al.

20S proteasome mediated degradation of DHFR: implications in neurodegenerative disorders.

The 20S proteasome is responsible for the degradation of protein substrates implicated in the onset and progression of neurodegenerative disorders, such as alpha-synuclein and tau protein. Here we show that the 20S proteasome isolated from bovine brain directly hydrolyzes, in vitro, the dihydrofolate reductase (DHFR), demonstrated to be involved in the pathogenesis of neurodegenerative diseases. Furthermore, the DHFR susceptibility to proteolysis is enhanced by oxidative conditions induced by peroxynitrite, mimicking the oxidative environment typical of these disorders.

Peroxynitrite-induced oxidation and its effects on isolated proteasomal systems.

The proteasomes are the major intracellular proteolytic systems involved in the removal of altered proteins. In this study, we examined different susceptibilities of constitutive (XYZ) and interferon-gamma inducible (LMP) 20S proteasomes, isolated from bovine brain and thymus, respectively, to peroxynitrite-mediated oxidation. Exposure of XYZ and LMP proteasomes to increasing amounts of peroxynitrite resulted in different levels, in the two enzymes, of 3-nitrotyrosine groups and tryptophan residues oxidation.