PMID- 28429668 OWN - NLM STAT- MEDLINE DCOM- 20180521 LR - 20180521 IS - 1875-5666 (Electronic) IS - 1566-5240 (Linking) VI - 17 IP - 2 DP - 2017 TI - The Role of Mitochondria-Associated Reactive Oxygen Species in the Amyloid beta Induced Production of Angiogenic Factors b y ARPE-19 Cells. PG - 140-148 LID - 10.2174/1566524017666170331162616 [doi] AB - OBJECTIVE: This study aimed to investigate the mechanisms whereby Amyloidbeta (Abeta) induces the production of angiogenic factors by a human retinal pigment epithelial cell line (ARPE-19) cells. METHODS: ARPE-19 cells obtained from the American Type Culture Collection (ATCC) were utilized in this study. The expression level of vascular endothelial growth factor (VEGF), Interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1) and complement activation fragments C3a and C5a were measured by Real-time quantitative PCR (RT-PCR) and Enzyme-linked immunosorbent assay (ELISA). The production of mitochondria-associated reactive oxygen species (ROS) was measured by flow cytometry. RESULTS: The expression of VEGF, IL-8, MCP-1, C3a and C5a was significantly increased in Abeta-treated ARPE-19 cells. Mitochondria-associated ROS production was also significantly increased when exposed to Abeta. Inhibition of mitochondrial ROS with Diphenyleneiodonium chloride (DPI) markedly decreased the Abeta induced production of VEGF, IL-8, MCP-1, C3a and C5a by ARPE-19 cells. Anti-C3a or anti-C5a neutralizing antibodies did not have a detectable influence on the secretion of VEGF, IL-8 and MCP-1 by ARPE-19 cells upon stimulation with Abeta. CONCLUSION: Our results support the hypothesis that Abeta is involved in the pathogenesis of choroidal neovascularization (CNV) formation by promoting the production of the angiogenic cytokines VEGF, IL-8 and MCP-1 by RPE cells. Mitochondrial ROS was shown to play a role in the regulation of Abeta induced expression of these cytokines. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.org. FAU - Wu, L AU - Wu L AD - The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing. China. FAU - Tan, X AU - Tan X AD - The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing. China. FAU - Liang, L AU - Liang L AD - The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing. China. FAU - Yu, H AU - Yu H AD - The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing. China. FAU - Wang, C AU - Wang C AD - The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing. China. FAU - Zhang, D AU - Zhang D AD - The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing. China. FAU - Kijlstra, A AU - Kijlstra A AD - Eye Research Institute Maastricht, Department of Ophthalmology, University Hospital Maastricht, Maastricht. Netherlands. FAU - Yang, P AU - Yang P AD - The First Affiliated Hospital of Chongqing Medical University, Youyi Road 1, Chongqing 400016, People's. China. LA - eng PT - Journal Article PL - Netherlands TA - Curr Mol Med JT - Current molecular medicine JID - 101093076 RN - 0 (Amyloid beta-Peptides) RN - 0 (Angiogenesis Inducing Agents) RN - 0 (Biomarkers) RN - 0 (Chemokine CCL2) RN - 0 (Interleukin-8) RN - 0 (Reactive Oxygen Species) RN - 0 (Vascular Endothelial Growth Factor A) RN - 80295-42-7 (Complement C3a) RN - 80295-54-1 (Complement C5a) SB - IM MH - Amyloid beta-Peptides/*metabolism MH - Angiogenesis Inducing Agents/*metabolism MH - Biomarkers MH - Cell Line MH - Cells, Cultured MH - Chemokine CCL2/genetics/metabolism MH - Complement C3a/immunology MH - Complement C5a/immunology MH - Humans MH - Interleukin-8/genetics/metabolism MH - Mitochondria/genetics/*metabolism MH - Reactive Oxygen Species/*metabolism MH - Retinal Pigment Epithelium/metabolism MH - Vascular Endothelial Growth Factor A/genetics/metabolism OTO - NOTNLM OT - Amyloid-beta OT - age-related macular degeneration OT - choroidal neovascularization OT - drusen OT - mitochondria-associated reactive oxygen species OT - retinal pigment epithelium EDAT- 2017/04/22 06:00 MHDA- 2018/05/22 06:00 CRDT- 2017/04/22 06:00 PHST- 2016/11/23 00:00 [received] PHST- 2017/02/18 00:00 [revised] PHST- 2017/02/21 00:00 [accepted] PHST- 2017/04/22 06:00 [pubmed] PHST- 2018/05/22 06:00 [medline] PHST- 2017/04/22 06:00 [entrez] AID - CMM-EPUB-82604 [pii] AID - 10.2174/1566524017666170331162616 [doi] PST - ppublish SO - Curr Mol Med. 2017;17(2):140-148. doi: 10.2174/1566524017666170331162616.