| http://purl.uniprot.org/citations/19815556 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/19815556 | http://www.w3.org/2000/01/rdf-schema#comment | "Seladin-1 is a neuroprotective protein selectively down-regulated in brain regions affected in Alzheimer disease (AD). Seladin-1 protects cells against beta-amyloid (Abeta) peptide 42- and oxidative stress-induced apoptosis activated by caspase-3, a key mediator of apoptosis. Here, we have employed RNA interference to assess the molecular effects of seladin-1 down-regulation on the beta-secretase (BACE1) function and beta-amyloid precursor protein (APP) processing in SH-SY5Y human neuroblastoma cells in both normal and apoptotic conditions. Our results show that approximately 60% reduction in seladin-1 protein levels, resembling the decrease observed in AD brain, did not significantly affect APP processing or Abeta secretion in normal growth conditions. However, under apoptosis, seladin-1 small interfering RNA (siRNA)-transfected cells showed increased caspase-3 activity on average by 2-fold when compared with control siRNA-transfected cells. Increased caspase-3 activity coincided with a significant depletion of the BACE1-sorting protein, GGA3 (Golgi-localized gamma-ear-containing ADP-ribosylation factor-binding protein), and subsequently augmented BACE1 protein levels and activity. Augmented BACE1 activity in turn correlated with the enhanced beta-amyloidogenic processing of APP and ultimately increased Abeta production. These adverse changes associated with decreased cell viability in seladin-1 siRNA-transfected cells under apoptosis. No changes in GGA3 or BACE1 levels were found after seladin-1 knockdown in normal growth conditions. Collectively, our results suggest that under stress conditions, reduced seladin-1 expression results in enhanced GGA3 depletion, which further leads to augmented post-translational stabilization of BACE1 and increased beta-amyloidogenic processing of APP. These mechanistic findings related to seladin-1 down-regulation are important in the context of AD as the oxidative stress-induced apoptosis plays a key role in the disease pathogenesis."xsd:string |
| http://purl.uniprot.org/citations/19815556 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m109.036202"xsd:string |
| http://purl.uniprot.org/citations/19815556 | http://purl.uniprot.org/core/author | "Hiltunen M."xsd:string |
| http://purl.uniprot.org/citations/19815556 | http://purl.uniprot.org/core/author | "Soininen H."xsd:string |
| http://purl.uniprot.org/citations/19815556 | http://purl.uniprot.org/core/author | "Haapasalo A."xsd:string |
| http://purl.uniprot.org/citations/19815556 | http://purl.uniprot.org/core/author | "Laitinen M."xsd:string |
| http://purl.uniprot.org/citations/19815556 | http://purl.uniprot.org/core/author | "Viswanathan J."xsd:string |
| http://purl.uniprot.org/citations/19815556 | http://purl.uniprot.org/core/author | "Makinen P."xsd:string |
| http://purl.uniprot.org/citations/19815556 | http://purl.uniprot.org/core/author | "Sarajarvi T."xsd:string |
| http://purl.uniprot.org/citations/19815556 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
| http://purl.uniprot.org/citations/19815556 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/19815556 | http://purl.uniprot.org/core/pages | "34433-34443"xsd:string |
| http://purl.uniprot.org/citations/19815556 | http://purl.uniprot.org/core/title | "Down-regulation of seladin-1 increases BACE1 levels and activity through enhanced GGA3 depletion during apoptosis."xsd:string |
| http://purl.uniprot.org/citations/19815556 | http://purl.uniprot.org/core/volume | "284"xsd:string |
| http://purl.uniprot.org/citations/19815556 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/19815556 |
| http://purl.uniprot.org/citations/19815556 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/19815556 |
| http://purl.uniprot.org/uniprot/#_P56817-mappedCitation-19815556 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19815556 |
| http://purl.uniprot.org/uniprot/#_A8K6I6-mappedCitation-19815556 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19815556 |
| http://purl.uniprot.org/uniprot/#_A0A7P0TAB4-mappedCitation-19815556 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19815556 |
| http://purl.uniprot.org/uniprot/#_B7Z7R9-mappedCitation-19815556 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19815556 |
| http://purl.uniprot.org/uniprot/#_A8K6M0-mappedCitation-19815556 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19815556 |
| http://purl.uniprot.org/uniprot/#_B7Z1E9-mappedCitation-19815556 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19815556 |
| http://purl.uniprot.org/uniprot/#_B7Z3K2-mappedCitation-19815556 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19815556 |
| http://purl.uniprot.org/uniprot/#_B7Z3Z4-mappedCitation-19815556 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19815556 |