Pharmacological protection of retinal pigmented epithelial cells by sulindac involves PPAR-α
The retinal pigmented epithelial (RPE) layer is one of the major ocular tissues affected by oxidative stress and is known to play an important role in the etiology of age-related macular degeneration (AMD), the major cause of blinding in the elderly. In the present study, sulindac, a nonsteroidal antiinflammatory drug (NSAID), was tested for protection against oxidative stressinduced damage in an established RPE cell line (ARPE-19). Besides its established antiinflammatory activity, sulindac has previously been shown to protect cardiac tissue against ischemia/reperf usion damage, although the exact mechanism was not elucidated. As shown here, sulindac can also protect RPE cells from chemical oxidative damage or UV light by initiating a protective mechanism similar to what is observed in ischemie preconditioning (IPC) response. The mechanism of protection appears to be triggered by reactive oxygen species (ROS) and involves known IPC signaling components such as PKG and PKC epsilon in addition to the mitochondrial ATP-sensitive K⁺ channel. Sulindac induced iNOS and Hsp70, late-phase IPC markers in the RPE cells. A unique feature of the sulindac protective response is that it involves activation of the peroxisome proliferator-activated receptor alpha (PPAR-α). We have also used low-passage human fetal RPE and polarized primary fetal RPE cells to validate the basic observation that sulindac can protect retinal cells against oxidative stress. These findings indicate a mechanism for preventing oxidative stress in RPE cells and suggest that sulindac could be used therapeutically for slowing the progression of AMD..
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2014 |
|---|---|
| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:111 |
|---|
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Sur, Arunodoy [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Applied sciences |
|---|
| Förderinstitution / Projekttitel: |
|
|---|
| PPN (Katalog-ID): |
JST114790671 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | JST114790671 | ||
| 003 | DE-627 | ||
| 005 | 20240117002514.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 180607s2014 xx |||||o 00| ||eng c | ||
| 035 | |a (DE-627)JST114790671 | ||
| 035 | |a (JST)43279384 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Sur, Arunodoy |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Pharmacological protection of retinal pigmented epithelial cells by sulindac involves PPAR-α |
| 264 | 1 | |c 2014 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a The retinal pigmented epithelial (RPE) layer is one of the major ocular tissues affected by oxidative stress and is known to play an important role in the etiology of age-related macular degeneration (AMD), the major cause of blinding in the elderly. In the present study, sulindac, a nonsteroidal antiinflammatory drug (NSAID), was tested for protection against oxidative stressinduced damage in an established RPE cell line (ARPE-19). Besides its established antiinflammatory activity, sulindac has previously been shown to protect cardiac tissue against ischemia/reperf usion damage, although the exact mechanism was not elucidated. As shown here, sulindac can also protect RPE cells from chemical oxidative damage or UV light by initiating a protective mechanism similar to what is observed in ischemie preconditioning (IPC) response. The mechanism of protection appears to be triggered by reactive oxygen species (ROS) and involves known IPC signaling components such as PKG and PKC epsilon in addition to the mitochondrial ATP-sensitive K⁺ channel. Sulindac induced iNOS and Hsp70, late-phase IPC markers in the RPE cells. A unique feature of the sulindac protective response is that it involves activation of the peroxisome proliferator-activated receptor alpha (PPAR-α). We have also used low-passage human fetal RPE and polarized primary fetal RPE cells to validate the basic observation that sulindac can protect retinal cells against oxidative stress. These findings indicate a mechanism for preventing oxidative stress in RPE cells and suggest that sulindac could be used therapeutically for slowing the progression of AMD. | ||
| 540 | |a copyright © 1993–2008 National Academy of Sciences of the United States of America | ||
| 650 | 4 | |a Biological sciences |x Biology |x Physiology |x Physiological regulation |x Homeostasis |x Metabolic stress |x Oxidative stress | |
| 650 | 4 | |a Health sciences |x Medical sciences |x Pharmaceutics |x Pharmacologic actions |x Drug effects |x Protective effects | |
| 650 | 4 | |a Biological sciences |x Biology |x Cytology |x Cell biology |x Cells |x Epithelial cells | |
| 650 | 4 | |a Biological sciences |x Biology |x Cytology |x Cell biology |x Cells |x Cultured cells |x Cell lines | |
| 650 | 4 | |a Biological sciences |x Biology |x Cytology |x Cell biology |x Cells |x Neurons | |
| 650 | 4 | |a Biological sciences |x Biology |x Cytology |x Cell biology |x Cell physiology |x Cell death |x Apoptosis | |
| 650 | 4 | |a Physical sciences |x Chemistry |x Chemical compounds |x Chemicals |x Free radicals |x Reactive oxygen species | |
| 650 | 4 | |a Physical sciences |x Chemistry |x Chemical compounds |x Agonists | |
| 650 | 4 | |a Applied sciences |x Engineering |x Industrial engineering |x Process engineering |x Preconditioning | |
| 650 | 4 | |a Biological sciences |x Biology |x Cytology |x Cell biology |x Cells |x Cultured cells | |
| 655 | 4 | |a research-article | |
| 700 | 1 | |a Kesaraju, Shailaja |e verfasserin |4 aut | |
| 700 | 1 | |a Prentice, Howard |e verfasserin |4 aut | |
| 700 | 1 | |a Ayyanathan, Kasirajan |e verfasserin |4 aut | |
| 700 | 1 | |a Baronas-Lowell, Diane |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Danhong |e verfasserin |4 aut | |
| 700 | 1 | |a Hinton, David R. |e verfasserin |4 aut | |
| 700 | 1 | |a Blanks, Janet |e verfasserin |4 aut | |
| 700 | 1 | |a Weissbach, Herbert |e verfasserin |4 aut | |
| 773 | 1 | 8 | |g volume:111 |g year:2014 |g number:47 |g pages:16754-16759 |
| 856 | 4 | 0 | |u https://www.jstor.org/stable/43279384 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_JST | ||
| 951 | |a AR | ||
| 952 | |d 111 |j 2014 |e 47 |h 16754-16759 | ||