Targeting Phospholipase D Pharmacologically Prevents Phagocytic Function Loss of Retinal Pigment Epithelium Cells Exposed to High Glucose Levels
We previously described the participation of canonical phospholipase D isoforms (PLD1 and PLD2) in the inflammatory response of retinal pigment epithelium (RPE) cells exposed to high glucose concentrations (HG). Here, we studied the role of the PLD pathway in RPE phagocytic function. For this purpos...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-10-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/19/11823 |
| _version_ | 1797478818877800448 |
|---|---|
| author | Vicente Bermúdez Paula Estefanía Tenconi María Sol Echevarría Aram Asatrian Jorgelina Muriel Calandria Norma María Giusto Nicolas Guillermo Bazan Melina Valeria Mateos |
| author_facet | Vicente Bermúdez Paula Estefanía Tenconi María Sol Echevarría Aram Asatrian Jorgelina Muriel Calandria Norma María Giusto Nicolas Guillermo Bazan Melina Valeria Mateos |
| author_sort | Vicente Bermúdez |
| collection | DOAJ |
| description | We previously described the participation of canonical phospholipase D isoforms (PLD1 and PLD2) in the inflammatory response of retinal pigment epithelium (RPE) cells exposed to high glucose concentrations (HG). Here, we studied the role of the PLD pathway in RPE phagocytic function. For this purpose, ARPE-19 cells were exposed to HG (33 mM) or to normal glucose concentration (NG, 5.5 mM) and phagocytosis was measured using pHrodo™ green bioparticles<sup>®</sup> or photoreceptor outer segments (POS). HG exposure for 48 and 72 h reduced phagocytic function of ARPE-19 cells, and this loss of function was prevented when cells were treated with 5 μM of PLD1 (VU0359595 or PLD1i) or PLD2 (VU0285655-1 or PLD2i) selective inhibitors. Furthermore, PLD1i and PLD2i did not affect RPE phagocytosis under physiological conditions and prevented oxidative stress induced by HG. In addition, we demonstrated PLD1 and PLD2 expression in ABC cells, a novel human RPE cell line. Under physiological conditions, PLD1i and PLD2i did not affect ABC cell viability, and partial silencing of both PLDs did not affect ABC cell POS phagocytosis. In conclusion, PLD1i and PLD2i prevent the loss of phagocytic function of RPE cells exposed to HG without affecting RPE function or viability under non-inflammatory conditions. |
| first_indexed | 2024-03-09T21:37:01Z |
| format | Article |
| id | doaj.art-22b2a5a85a9740fd8e9b48c55343d6f1 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:37:01Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-22b2a5a85a9740fd8e9b48c55343d6f12023-11-23T20:39:53ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123191182310.3390/ijms231911823Targeting Phospholipase D Pharmacologically Prevents Phagocytic Function Loss of Retinal Pigment Epithelium Cells Exposed to High Glucose LevelsVicente Bermúdez0Paula Estefanía Tenconi1María Sol Echevarría2Aram Asatrian3Jorgelina Muriel Calandria4Norma María Giusto5Nicolas Guillermo Bazan6Melina Valeria Mateos7Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Bahía Blanca 8000, ArgentinaInstituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Bahía Blanca 8000, ArgentinaInstituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Bahía Blanca 8000, ArgentinaNeuroscience Center of Excellence, School of Medicine, Louisiana State University Health New Orleans, New Orleans, LA 70112, USANeuroscience Center of Excellence, School of Medicine, Louisiana State University Health New Orleans, New Orleans, LA 70112, USAInstituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Bahía Blanca 8000, ArgentinaNeuroscience Center of Excellence, School of Medicine, Louisiana State University Health New Orleans, New Orleans, LA 70112, USAInstituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Bahía Blanca 8000, ArgentinaWe previously described the participation of canonical phospholipase D isoforms (PLD1 and PLD2) in the inflammatory response of retinal pigment epithelium (RPE) cells exposed to high glucose concentrations (HG). Here, we studied the role of the PLD pathway in RPE phagocytic function. For this purpose, ARPE-19 cells were exposed to HG (33 mM) or to normal glucose concentration (NG, 5.5 mM) and phagocytosis was measured using pHrodo™ green bioparticles<sup>®</sup> or photoreceptor outer segments (POS). HG exposure for 48 and 72 h reduced phagocytic function of ARPE-19 cells, and this loss of function was prevented when cells were treated with 5 μM of PLD1 (VU0359595 or PLD1i) or PLD2 (VU0285655-1 or PLD2i) selective inhibitors. Furthermore, PLD1i and PLD2i did not affect RPE phagocytosis under physiological conditions and prevented oxidative stress induced by HG. In addition, we demonstrated PLD1 and PLD2 expression in ABC cells, a novel human RPE cell line. Under physiological conditions, PLD1i and PLD2i did not affect ABC cell viability, and partial silencing of both PLDs did not affect ABC cell POS phagocytosis. In conclusion, PLD1i and PLD2i prevent the loss of phagocytic function of RPE cells exposed to HG without affecting RPE function or viability under non-inflammatory conditions.https://www.mdpi.com/1422-0067/23/19/11823phospholipase D (PLD)retinal pigment epithelium (RPE)phagocytosisinflammationoxidative stress |
| spellingShingle | Vicente Bermúdez Paula Estefanía Tenconi María Sol Echevarría Aram Asatrian Jorgelina Muriel Calandria Norma María Giusto Nicolas Guillermo Bazan Melina Valeria Mateos Targeting Phospholipase D Pharmacologically Prevents Phagocytic Function Loss of Retinal Pigment Epithelium Cells Exposed to High Glucose Levels International Journal of Molecular Sciences phospholipase D (PLD) retinal pigment epithelium (RPE) phagocytosis inflammation oxidative stress |
| title | Targeting Phospholipase D Pharmacologically Prevents Phagocytic Function Loss of Retinal Pigment Epithelium Cells Exposed to High Glucose Levels |
| title_full | Targeting Phospholipase D Pharmacologically Prevents Phagocytic Function Loss of Retinal Pigment Epithelium Cells Exposed to High Glucose Levels |
| title_fullStr | Targeting Phospholipase D Pharmacologically Prevents Phagocytic Function Loss of Retinal Pigment Epithelium Cells Exposed to High Glucose Levels |
| title_full_unstemmed | Targeting Phospholipase D Pharmacologically Prevents Phagocytic Function Loss of Retinal Pigment Epithelium Cells Exposed to High Glucose Levels |
| title_short | Targeting Phospholipase D Pharmacologically Prevents Phagocytic Function Loss of Retinal Pigment Epithelium Cells Exposed to High Glucose Levels |
| title_sort | targeting phospholipase d pharmacologically prevents phagocytic function loss of retinal pigment epithelium cells exposed to high glucose levels |
| topic | phospholipase D (PLD) retinal pigment epithelium (RPE) phagocytosis inflammation oxidative stress |
| url | https://www.mdpi.com/1422-0067/23/19/11823 |
| work_keys_str_mv | AT vicentebermudez targetingphospholipasedpharmacologicallypreventsphagocyticfunctionlossofretinalpigmentepitheliumcellsexposedtohighglucoselevels AT paulaestefaniatenconi targetingphospholipasedpharmacologicallypreventsphagocyticfunctionlossofretinalpigmentepitheliumcellsexposedtohighglucoselevels AT mariasolechevarria targetingphospholipasedpharmacologicallypreventsphagocyticfunctionlossofretinalpigmentepitheliumcellsexposedtohighglucoselevels AT aramasatrian targetingphospholipasedpharmacologicallypreventsphagocyticfunctionlossofretinalpigmentepitheliumcellsexposedtohighglucoselevels AT jorgelinamurielcalandria targetingphospholipasedpharmacologicallypreventsphagocyticfunctionlossofretinalpigmentepitheliumcellsexposedtohighglucoselevels AT normamariagiusto targetingphospholipasedpharmacologicallypreventsphagocyticfunctionlossofretinalpigmentepitheliumcellsexposedtohighglucoselevels AT nicolasguillermobazan targetingphospholipasedpharmacologicallypreventsphagocyticfunctionlossofretinalpigmentepitheliumcellsexposedtohighglucoselevels AT melinavaleriamateos targetingphospholipasedpharmacologicallypreventsphagocyticfunctionlossofretinalpigmentepitheliumcellsexposedtohighglucoselevels |