DEL-1: a promising treatment for AMD-associated ER stress in retinal pigment epithelial cells
Abstract Background Age-related macular degeneration (AMD) is an irreversible eye disease that can cause blurred vision. Regular exercise has been suggested as a therapeutic strategy for treating AMD, but how exercise improves AMD is not yet understood. This study investigated the protective effects...
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-024-04858-9 |
| _version_ | 1797355611366621184 |
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| author | ChangHyuk Kwon Wonjun Cho Sung Woo Choi Heeseung Oh A. M. Abd El-Aty Ibrahim Gecili Ji Hoon Jeong Tae Woo Jung |
| author_facet | ChangHyuk Kwon Wonjun Cho Sung Woo Choi Heeseung Oh A. M. Abd El-Aty Ibrahim Gecili Ji Hoon Jeong Tae Woo Jung |
| author_sort | ChangHyuk Kwon |
| collection | DOAJ |
| description | Abstract Background Age-related macular degeneration (AMD) is an irreversible eye disease that can cause blurred vision. Regular exercise has been suggested as a therapeutic strategy for treating AMD, but how exercise improves AMD is not yet understood. This study investigated the protective effects of developmental endothelial locus-1 (DEL-1), a myokine upregulated during exercise, on endoplasmic reticulum (ER) stress-induced injury in retinal pigment epithelial cells. Methods We evaluated the levels of AMPK phosphorylation, autophagy markers, and ER stress markers in DEL-1-treated human retinal pigment epithelial cells (hRPE) using Western blotting. We also performed cell viability, caspase 3 activity assays, and autophagosome staining. Results Our findings showed that treatment with recombinant DEL-1 dose-dependently reduced the impairment of cell viability and caspase 3 activity in tunicamycin-treated hRPE cells. DEL-1 treatment also alleviated tunicamycin-induced ER stress markers and VEGF expression. Moreover, AMPK phosphorylation and autophagy markers were increased in hRPE cells in the presence of DEL-1. However, the effects of DEL-1 on ER stress, VEGF expression, and apoptosis in tunicamycin-treated hRPE cells were reduced by AMPK siRNA or 3-methyladenine (3-MA), an autophagy inhibitor. Conclusions Our study suggests that DEL-1, a myokine, may have potential as a treatment strategy for AMD by attenuating ER stress-induced injury in retinal pigment epithelial cells. |
| first_indexed | 2024-03-08T14:13:39Z |
| format | Article |
| id | doaj.art-e36d025575ff4edaa4c79079c1055e59 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-08T14:13:39Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-e36d025575ff4edaa4c79079c1055e592024-01-14T12:34:30ZengBMCJournal of Translational Medicine1479-58762024-01-0122111010.1186/s12967-024-04858-9DEL-1: a promising treatment for AMD-associated ER stress in retinal pigment epithelial cellsChangHyuk Kwon0Wonjun Cho1Sung Woo Choi2Heeseung Oh3A. M. Abd El-Aty4Ibrahim Gecili5Ji Hoon Jeong6Tae Woo Jung7GenesisEgoDepartment of Pharmacology, College of Medicine, Chung-Ang UniversityDepartment of Pharmacology, College of Medicine, Chung-Ang UniversityDepartment of Pharmacology, College of Medicine, Chung-Ang UniversityDepartment of Pharmacology, Faculty of Veterinary Medicine, Cairo UniversityDepartment of Medical Pharmacology, Medical Faculty, Ataturk UniversityDepartment of Pharmacology, College of Medicine, Chung-Ang UniversityDepartment of Pharmacology, College of Medicine, Chung-Ang UniversityAbstract Background Age-related macular degeneration (AMD) is an irreversible eye disease that can cause blurred vision. Regular exercise has been suggested as a therapeutic strategy for treating AMD, but how exercise improves AMD is not yet understood. This study investigated the protective effects of developmental endothelial locus-1 (DEL-1), a myokine upregulated during exercise, on endoplasmic reticulum (ER) stress-induced injury in retinal pigment epithelial cells. Methods We evaluated the levels of AMPK phosphorylation, autophagy markers, and ER stress markers in DEL-1-treated human retinal pigment epithelial cells (hRPE) using Western blotting. We also performed cell viability, caspase 3 activity assays, and autophagosome staining. Results Our findings showed that treatment with recombinant DEL-1 dose-dependently reduced the impairment of cell viability and caspase 3 activity in tunicamycin-treated hRPE cells. DEL-1 treatment also alleviated tunicamycin-induced ER stress markers and VEGF expression. Moreover, AMPK phosphorylation and autophagy markers were increased in hRPE cells in the presence of DEL-1. However, the effects of DEL-1 on ER stress, VEGF expression, and apoptosis in tunicamycin-treated hRPE cells were reduced by AMPK siRNA or 3-methyladenine (3-MA), an autophagy inhibitor. Conclusions Our study suggests that DEL-1, a myokine, may have potential as a treatment strategy for AMD by attenuating ER stress-induced injury in retinal pigment epithelial cells.https://doi.org/10.1186/s12967-024-04858-9DEL-1Retinal pigment epithelial cellsAMDER stressAutophagyApoptosis |
| spellingShingle | ChangHyuk Kwon Wonjun Cho Sung Woo Choi Heeseung Oh A. M. Abd El-Aty Ibrahim Gecili Ji Hoon Jeong Tae Woo Jung DEL-1: a promising treatment for AMD-associated ER stress in retinal pigment epithelial cells Journal of Translational Medicine DEL-1 Retinal pigment epithelial cells AMD ER stress Autophagy Apoptosis |
| title | DEL-1: a promising treatment for AMD-associated ER stress in retinal pigment epithelial cells |
| title_full | DEL-1: a promising treatment for AMD-associated ER stress in retinal pigment epithelial cells |
| title_fullStr | DEL-1: a promising treatment for AMD-associated ER stress in retinal pigment epithelial cells |
| title_full_unstemmed | DEL-1: a promising treatment for AMD-associated ER stress in retinal pigment epithelial cells |
| title_short | DEL-1: a promising treatment for AMD-associated ER stress in retinal pigment epithelial cells |
| title_sort | del 1 a promising treatment for amd associated er stress in retinal pigment epithelial cells |
| topic | DEL-1 Retinal pigment epithelial cells AMD ER stress Autophagy Apoptosis |
| url | https://doi.org/10.1186/s12967-024-04858-9 |
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