Blood-brain barrier (BBB) breakdown has been determined to play a critical role in the pathogenesis of Alzheimer's disease (AD). However, the underlying mechanisms of BBB disruption in AD remain unclear. Our previous study suggested that the receptor for advanced glycation end-products (RAGE) functioned as a signal transduction receptor in Aβ1–42-induced damage in endothelial cells. In our present study, we revealed that RAGE-mediated endoplasmic reticulum stress (ERS) is essential for Aβ-induced endothelial cell damage. Here, we found that Aβ1–42 activated ERS by upregulation of Grp78, xbp-1 and CHOP in endothelial cells and that Aβ1–42-resulted lesions, including the upregulations of caspase-12 and caspase-3, the augment of bax/bcl-2 ratio, and the downregulations of ZO-1 and Occludin in bEnd.3 cells, were ameliorated by the pretreatment of salubrinal, an ERS inhibitor. Furthermore, the expressions of Grp78, xbp-1 and CHOP induced by Aβ1–42 were blocked by transfection of RAGE small interfering RNA (siRNA), which indicated that Aβ1–42 activated ERS in a RAGE-dependent manner. Additionally, bEnd.3 cells transfected with RAGE siRNA showed lower expressions of caspase-12 and caspase-3, decreased bax/bcl-2 ratio, and higher expressions of ZO-1 and Occludin following Aβ1-42 treatment, comparing to control cells. In conclusion, our data demonstrated that Aβ1–42 induced endothelial cells damage via activation of ERS in a RAGE-dependent manner. 相似文献
Thermal stress is considered one of the main causes of mass scleractinian coral degradation; however, it is still unknown how corals can adapt to future global warming. In this study, 11 strains of coral-associated Flavobacteria were shown to produce zeaxanthin, a carotenoid antioxidant, which may help coral holobionts to alleviate thermal stress. In addition, a novel zeaxanthin-producing Flavobacterium, designated R38T, was identified using polyphasic taxonomy. Although strain R38T shared a maximum 16S rRNA gene sequence similarity of 93% with Mesoflavibacter aestuarii KYW614T, phylogenetic analyses based on whole genome and 16S rRNA gene sequences revealed that strain R38T forms a distinct branch in a robust cluster composed of strain R38T and Leptobacterium flavescens KCTC 22160T under the family Flavobacteriaceae. Strain R38T exhibited average nucleotide identities of 70.2% and 72.5% for M. aestuarii KYW614T and L. flavescens KCTC 22160T, respectively. The only detected respiratory quinone was menaquinone 6 (MK-6). The genomic DNA G?+?C content was 33.2 mol%. The major polar lipids were phosphatidylmethylethanolamine, phosphatidylethanolamine, one unidentified ninhydrin phospholipid, three unidentified ninhydrin-positive lipids, and three unidentified lipids. The major cellular fatty acids were iso???C15:?0, iso???C15:?0 ω6c, C16:2 DMA, and C13:1 ω3c. The distinct biochemical, chemotaxonomic, phylogenetic, and phylogenomic differences from validly published taxa suggest that strain R38T represents a new species of a new genus, for which Prasinibacter corallicola gen. nov., sp. nov. is proposed. The type strain R38T (=?MCCC 1K03889T?=?KCTC 72444T).