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Cathepsin X promotes 6-hydroxydopamine-induced apoptosis of PC12 and SH-SY5Y cellsPišlar, Anja ...The cysteine carboxypeptidase cathepsin X is an important player in degenerative processes under normal ageing and pathological conditions. In the present study, we investigated the potential role of ... cathepsin X in 6-hydroxydopamine (6-OHDA)-induced toxicity in the pheochromocytoma cell line PC12 and neuroblastoma cell line SH-SY5Y. Cells exposed to 6-OHDA demonstrated alterations in the protein level of cathepsin X and activity of cathepsin X. Down regulation of cathepsin X expression by siRNA attenuated the neuronal death caused by 6-OHDA. Treatment with specific cathepsin X inhibitor AMS36 protected cells against 6-OHDA mediated cytotoxicity, resulting in reduced cell death and apoptosis. Furthermore, AMS36 reversed 6-OHDA-induced loss of tyrosine hydroxylase and attenuated 6-OHDA-induced activation of caspase-3, triggering apoptosis, intracellular generation of reactive oxygen species and mitochondrial dysfunction, including the release of cytochrome c and an imbalanced Bax/Bcl-2 ratio. Moreover, AMS36 interfered with NF-kB activation by blocking degradation of IkB[alpha], preventing NF-kB translocation to the nucleus. Our data provide the first evidence that inhibition of cathepsin X protects both, PC12 and SH-SY5Y cells against 6-OHDA toxicity and indicate that cathepsin X may be responsible for dopamine neuron death, involved in the pathogenic cascade event for the neurodegenerative disorders, such as Parkinson's disease.Source: Neuropharmacology. - ISSN 0028-3908 (Vol. 82, 2014, str. 121-131)Type of material - article, component partPublish date - 2014Language - englishCOBISS.SI-ID - 3499889
Author
Pišlar, Anja |
Zidar, Nace |
Kikelj, Danijel |
Kos, Janko, 1959-
Topics
cathepsin X |
6-hydroxydopamine |
apoptosis |
mitochondrial dysfunction |
neuroprotection
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Pišlar, Anja | 32035 |
Zidar, Nace | 28905 |
Kikelj, Danijel | 01463 |
Kos, Janko, 1959- | 04648 |
Source: Personal bibliographies
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