78 research outputs found
Inhibition of protein ubiquitination by paraquat and 1-methyl-4-phenylpyridinium impairs ubiquitin-dependent protein degradation pathways
Intracytoplasmic inclusions of protein aggregates in dopaminergic cells (Lewy bodies) are the pathological hallmark of Parkinson’s disease (PD). Ubiquitin (Ub), alpha [α]-synuclein, p62/sequestosome 1 and oxidized proteins are major components of Lewy bodies. However, the mechanisms involved in the impairment of misfolded/oxidized protein degradation pathways in PD are still unclear. PD is linked to mitochondrial dysfunction and environmental pesticide exposure. In this work, we evaluated the effect of the pesticide paraquat (PQ) and the mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP+) on Ub-dependent protein degradation pathways. No increase in the accumulation of Ub-bound proteins or aggregates was observed in dopaminergic cells (SK-N-SH) treated with PQ or MPP+, or in mice chronically exposed to PQ. PQ decreased Ub protein content, but not its mRNA transcription. Protein synthesis inhibition with cycloheximide depleted Ub levels and potentiated PQ–induced cell death. Inhibition of proteasomal activity by PQ was found to be a late event in cell death progression, and had no effect on either the toxicity of MPP+ or PQ, or the accumulation of oxidized sulfenylated, sulfonylated (DJ-1/PARK7 and peroxiredoxins) and carbonylated proteins induced by PQ. PQ- and MPP+-induced Ub protein depletion prompted the dimerization/inactivation of the Ub-binding protein p62 that regulates the clearance of ubiquitinated proteins by autophagic. We confirmed that PQ and MPP+ impaired autophagy flux, and that the blockage of autophagy by the overexpression of a dominant-negative form of the autophagy protein 5 (dnAtg5) stimulated their toxicity, but there was no additional effect upon inhibition of the proteasome. PQ induced an increase in the accumulation of α-synuclein in dopaminergic cells and membrane associated foci in yeast cells. Our results demonstrate that inhibition of protein ubiquitination by PQ and MPP+ is involved in the dysfunction of Ub-dependent protein degradation pathways
Eine kolorimetrische Methode zur Bestimmung der St�rke von S�uren unter Verwendung von Pflanzenfarbstoffen
X-ray photoelectron spectroscopy study on gold nanoparticles supported on diamond
By exploiting the self-organization of metal salt-loaded diblock copolymer micelles followed by a plasma-induced removal of the polymer matrix, well-separated gold particles ranging in size from 1.6 to 10 nm have been prepared on top of diamond substrates. X-ray-induced photoelectron spectra of the valence-band region demonstrate that the electronic properties of such nanoparticles essentially reflect the metallic behavior of the bulk material as can be inferred from the evolution of the d-band shape and the finite density of states at the Fermi energy. This experimentally extends the lower limit for the metallic state of supported Au particles down to a diameter of 1.6 nm
Verzögerung des katalytischen Wasserstoffperoxyd-Zerfalles durch Gifte als Untersuchungsmethodik an AbwÄssern
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