leupeptins has been researched along with 3-nitropropionic-acid* in 2 studies
2 other study(ies) available for leupeptins and 3-nitropropionic-acid
| Article | Year |
|---|---|
Proteasome activator enhances survival of Huntington's disease neuronal model cells.
In patients with Huntington's disease (HD), the proteolytic activity of the ubiquitin proteasome system (UPS) is reduced in the brain and other tissues. The pathological hallmark of HD is the intraneuronal nuclear protein aggregates of mutant huntingtin. We determined how to enhance UPS function and influence catalytic protein degradation and cell survival in HD. Proteasome activators involved in either the ubiquitinated or the non-ubiquitinated proteolysis were overexpressed in HD patients' skin fibroblasts or mutant huntingtin-expressing striatal neurons. Following compromise of the UPS, overexpression of the proteasome activator subunit PA28gamma, but not subunit S5a, recovered proteasome function in the HD cells. PA28gamma also improved cell viability in mutant huntingtin-expressing striatal neurons exposed to pathological stressors, such as the excitotoxin quinolinic acid and the reversible proteasome inhibitor MG132. These results demonstrate the specific functional enhancements of the UPS that can provide neuroprotection in HD cells. Topics: Cell Survival; Cells, Cultured; Corpus Striatum; Fibroblasts; Humans; Huntingtin Protein; Huntington Disease; Leupeptins; Muscle Proteins; Nerve Tissue Proteins; Neurons; Nitro Compounds; Nuclear Proteins; Peptide Fragments; Propionates; Proteasome Endopeptidase Complex; Quinolinic Acid; Recombinant Fusion Proteins; RNA-Binding Proteins; Transduction, Genetic; Ubiquitin; Up-Regulation | 2007 |
Depressant effect of mitochondrial respiratory complex inhibitors on proteasome inhibitor-induced mitochondrial dysfunction and cell death in PC12 cells.
The addition of rotenone (inhibitor of respiratory complex I), 3-nitropropionic acid (complex II inhibitor), harmine (inhibitor of complexes I and II) and cyclosporin A (CsA, an inhibitor of the mitochondrial permeability transition) reduced the nuclear damage, loss in the mitochondrial transmembrane potential, cytosolic accumulation of cytochrome c, activation of caspase-3, increase in the formation of reactive oxygen species and depletion of GSH in differentiated PC12 cells treated with MG132, a proteasome inhibitor. Meanwhile, rotenone, 3-nitropropionic acid and harmine did not affect the inhibitory effect of CsA or trifluoperazine (an inhibitor of the mitochondrial permeability transition and calmodulin antagonist) on the cytotoxicity of MG132. The results suggest that proteasome inhibition-induced mitochondrial dysfunction and cell injury may be attenuated by the inhibitions of respiratory chain complex I and II. The cytoprotective effect of the mitochondrial permeability transition prevention not appears to be modulated by respiratory complex inhibition. Topics: Animals; Cell Death; Cell Membrane Permeability; Cyclosporine; Electron Transport; Enzyme Inhibitors; Glutathione; Harmine; Humans; Leupeptins; Mitochondria; Nitro Compounds; PC12 Cells; Propionates; Proteasome Inhibitors; Rats; Reactive Oxygen Species; Rotenone; Trifluoperazine; Uncoupling Agents | 2005 |