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Oxidative stress-mediated TXNIP loss causes RPE dysfunction
Min Ji Cho,Sung-Jin Yoon,Wooil Kim,Jongjin Park,Jangwook Lee,Jong-Gil Park,Young-Lai Cho,Jeong Hun Kim,Hyejin Jang,박영준,이상현,Jeong-Ki Min 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-
The disruption of the retinal pigment epithelium (RPE), for example, through oxidative damage, is a common factorunderlying age-related macular degeneration (AMD). Aberrant autophagy also contributes to AMD pathology, asautophagy maintains RPE homeostasis to ensure blood–retinal barrier (BRB) integrity and protect photoreceptors. Thioredoxin-interacting protein (TXNIP) promotes cellular oxidative stress by inhibiting thioredoxin reducing capacityand is in turn inversely regulated by reactive oxygen species levels; however, its role in oxidative stress-induced RPEcell dysfunction and the mechanistic link between TXNIP and autophagy are largely unknown. Here, we observed thatTXNIP expression was rapidly downregulated in RPE cells under oxidative stress and that RPE cell proliferation wasdecreased. TXNIP knockdown demonstrated that the suppression of proliferation resulted from TXNIP depletioninducedautophagic flux, causing increased p53 activation via nuclear localization, which in turn enhanced AMPKphosphorylation and activation. Moreover, TXNIP downregulation further negatively impacted BRB integrity bydisrupting RPE cell tight junctions and enhancing cell motility by phosphorylating, and thereby activating, Src kinase. Finally, we also revealed that TXNIP knockdown upregulated HIF-1α, leading to the enhanced secretion of VEGF fromRPE cells and the stimulation of angiogenesis in cocultured human retinal microvascular endothelial cells. Thissuggests that the exposure of RPE cells to sustained oxidative stress may promote choroidal neovascularization,another AMD pathology. Together, these findings reveal three distinct mechanisms by which TXNIP downregulationdisrupts RPE cell function and thereby exacerbates AMD pathogenesis. Accordingly, reinforcing or restoring BRBintegrity by targeting TXNIP may serve as an effective therapeutic strategy for preventing or attenuatingphotoreceptor damage in AMD.
Hyejin Mo,Juhan Lee,Jae Berm Park,Sun Cheol Park,Young Hoon Kim,Ahram Han,In Mok Jung,Jongwon Ha,Nam-Joong Kim,Sang Il Min 대한의학회 2022 Journal of Korean medical science Vol.37 No.1
Background: The use of organs from donors with infection is limited because of the possibility of transmission. We aimed to investigate the transmission after deceased donor transplantation with bloodstream infection (BSI). Methods: A retrospective study of patients undergoing kidney or pancreas transplantation at five tertiary centers in Korea from January 2009 and November 2019 was performed. We analyzed the outcomes after transplantation from deceased donors with BSI. Results: Eighty-six recipients received transplantation from 69 donors with BSI. The most common isolated pathogens from donors were Gram-positive bacteria (72.0%), followed by Gram-negative bacteria (22.7%), and fungi (5.3%). Appropriate antimicrobial agents were used in 47.8% of donors before transplantation. Transmission occurred only in 1 of 83 recipients (1.2%) from bacteremic donors and 1 of 6 recipients (16.7%) from fungemic donors. One-year patient and graft survival was 97.5%and 96.3%, respectively. There was no significant difference in graft and patient survival between patients who received organs from infected donors and noninfected donors. Conclusion: Using organs from donors with bacteremia seems to be a safe option with low transmission risk. The overall prognosis of using organs from donors with BSI is favorable.