| http://purl.uniprot.org/citations/23538444 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23538444 | http://www.w3.org/2000/01/rdf-schema#comment | "Netrin (Ntn) has the potential to be successfully applied as an anti-apoptotic agent with a high affinity for tissue, for therapeutic strategies of umbilical cord blood-derived mesenchymal stem cells (UCB-MSC), although the mechanism by which Ntn-1 protects hypoxic injury has yet to be identified. Therefore, the present study examined the effect of Ntn-1 on hypoxia-induced UCB-MSC apoptosis, as well as the potential underlying mechanisms of its protective effect. Hypoxia (72 h) reduced cell viability (MTT reduction, and [(3)H]-thymidine incorporation) and cell number, and induced apoptosis (annexin and/or PI positive), which were reversed by Ntn-1 (10 ng/ml). Moreover, Ntn-1 decreased the increase of hypoxia-induced Bax, cleaved caspase-9, and -3, but blocked the decrease of hypoxia-reduced Bcl-2. Next, in order to examine the Ntn-1-related signaling cascade in the protection of hypoxic injury, we analyzed six Ntn receptors in UCB-MSC. We identified deleted in colorectal cancer (DCC) and integrin (IN) α6β4, except uncoordinated family member (UNC) 5A-C, and neogenin. Among them, IN α6β4 only was detected in lipid raft fractions. In addition, Ntn-1 induced the dissociation of DCC and APPL-1 complex, thereby stimulating the formation of APPL-1 and Akt2 complex. Ntn-1 also reversed the hypoxia-induced decrease of Akt and glycogen synthase kinase 3β (GSK-3β) phosphorylation, which is involved in heat shock factor-1 (HSF-1) expression. Ntn-1-induced phospho-Akt and -GSK-3β were inhibited by DCC function-blocking antibody, IN a6b4 function-blocking antibody, and the Akt inhibitor. Hypoxia and/or Ntn-1 stimulated heat shock protein (HSP)27 expression, which was blocked by HSF-1-specific small interfering RNA (siRNA). Furthermore, HSP27-specific siRNA reversed the Ntn-1-induced increase of phospho-Akt. Additionally, HSP27-specific siRNA attenuated the Ntn-1-reduced loss of mitochondrial membrane injury via the inhibition of cytochrome c (cyt c) release and formation of cyt c and HSP27 complex. Moreover, the inhibition of each signaling protein attenuated Ntn-1-induced blockage of apoptosis. In conclusion, Ntn-1-induced HSP27 protected hypoxic injury-related UCB-MSC apoptosis through DCC- and IN α6β4-dependent Akt, GSK-3β, and HSF-1 signaling pathways."xsd:string |
| http://purl.uniprot.org/citations/23538444 | http://purl.org/dc/terms/identifier | "doi:10.1038/cddis.2013.94"xsd:string |
| http://purl.uniprot.org/citations/23538444 | http://purl.uniprot.org/core/author | "Han H.J."xsd:string |
| http://purl.uniprot.org/citations/23538444 | http://purl.uniprot.org/core/author | "Ryu J.M."xsd:string |
| http://purl.uniprot.org/citations/23538444 | http://purl.uniprot.org/core/author | "Oh Y.M."xsd:string |
| http://purl.uniprot.org/citations/23538444 | http://purl.uniprot.org/core/author | "Youn H.Y."xsd:string |
| http://purl.uniprot.org/citations/23538444 | http://purl.uniprot.org/core/author | "Yun S.P."xsd:string |
| http://purl.uniprot.org/citations/23538444 | http://purl.uniprot.org/core/author | "Seo B.N."xsd:string |
| http://purl.uniprot.org/citations/23538444 | http://purl.uniprot.org/core/author | "Son T.W."xsd:string |
| http://purl.uniprot.org/citations/23538444 | http://purl.uniprot.org/core/author | "Yong M.S."xsd:string |
| http://purl.uniprot.org/citations/23538444 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23538444 | http://purl.uniprot.org/core/name | "Cell Death Dis"xsd:string |
| http://purl.uniprot.org/citations/23538444 | http://purl.uniprot.org/core/pages | "e563"xsd:string |
| http://purl.uniprot.org/citations/23538444 | http://purl.uniprot.org/core/title | "Netrin-1 protects hypoxia-induced mitochondrial apoptosis through HSP27 expression via DCC- and integrin alpha6beta4-dependent Akt, GSK-3beta, and HSF-1 in mesenchymal stem cells."xsd:string |
| http://purl.uniprot.org/citations/23538444 | http://purl.uniprot.org/core/volume | "4"xsd:string |
| http://purl.uniprot.org/citations/23538444 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23538444 |
| http://purl.uniprot.org/citations/23538444 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/23538444 |
| http://purl.uniprot.org/uniprot/#_O95631-mappedCitation-23538444 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23538444 |
| http://purl.uniprot.org/uniprot/O95631 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/23538444 |