Glycine-Conjugated Bile Acids Protect RPE Tight Junctions against Oxidative Stress and Inhibit Choroidal Endothelial Cell Angiogenesis In Vitro
| Autor: | Milam A. Brantley, Cassandra Warden |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Vascular Endothelial Growth Factor A Angiogenesis Cell Culture Techniques Angiogenesis Inhibitors Retinal Pigment Epithelium Biochemistry chemistry.chemical_compound angiogenesis 0302 clinical medicine Cell Movement Tube formation Tight junction Bile acid Neovascularization Pathologic Chemistry Ursodeoxycholic Acid QR1-502 Cell biology Endothelial stem cell Glycodeoxycholic acid Glycodeoxycholic Acid cardiovascular system RPE Glycocholic Acid medicine.drug_class Glycocholic acid Glycine choroidal endothelial cell Microbiology Article Tight Junctions Bile Acids and Salts 03 medical and health sciences medicine Animals Humans GCA Molecular Biology age-related macular degeneration Cell Proliferation bile acids Choroid Endothelial Cells Taurocholic acid Macaca mulatta Oxidative Stress 030104 developmental biology GUDCA 030221 ophthalmology & optometry Wet Macular Degeneration GDCA |
| Zdroj: | Biomolecules Biomolecules, Vol 11, Iss 626, p 626 (2021) Volume 11 Issue 5 |
| ISSN: | 2218-273X |
| Popis: | We previously demonstrated that the bile acid taurocholic acid (TCA) inhibits features of age-related macular degeneration (AMD) in vitro. The purpose of this study was to determine if the glycine-conjugated bile acids glycocholic acid (GCA), glycodeoxycholic acid (GDCA), and glycoursodeoxycholic acid (GUDCA) can protect retinal pigment epithelial (RPE) cells against oxidative damage and inhibit vascular endothelial growth factor (VEGF)-induced angiogenesis in choroidal endothelial cells (CECs). Paraquat was used to induce oxidative stress and disrupt tight junctions in HRPEpiC primary human RPE cells. Tight junctions were assessed via transepithelial electrical resistance and ZO-1 immunofluorescence. GCA and GUDCA protected RPE tight junctions against oxidative damage at concentrations of 100–500 µM, and GDCA protected tight junctions at 10–500 µM. Angiogenesis was induced with VEGF in RF/6A macaque CECs and evaluated with cell proliferation, cell migration, and tube formation assays. GCA inhibited VEGF-induced CEC migration at 50–500 µM and tube formation at 10–500 µM. GUDCA inhibited VEGF-induced CEC migration at 100–500 µM and tube formation at 50–500 µM. GDCA had no effect on VEGF-induced angiogenesis. None of the three bile acids significantly inhibited VEGF-induced CEC proliferation. These results suggest glycine-conjugated bile acids may be protective against both atrophic and neovascular AMD. |
| Databáze: | OpenAIRE |
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