MAP kinase pathways in UV-induced apoptosis of retinal pigment epithelium ARPE19 cells

Roduit, Raphaël; Schorderet, Daniel F.

doi:10.1007/s10495-008-0179-8

Cited by 97 publications

(86 citation statements)

References 48 publications

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“…The ERK pathway plays a major role in regulating cell growth, survival and differentiation (5), whereas EGCG protects against UVB-induced apoptosis via oxidative stress and the JNK1/c-Jun pathway in ARPE19 cells JNK and p38 are activated by stress signals, and the activation of these kinases is strongly associated with cell apoptosis (6,7). These UV-activated signal transduction pathways are mediated primarily through signaling cascades involving MAPKs (8), and MAPKs are activated in the UVC-induced apoptosis of ARPE19 cells (9). Oxidative stress, which refers to cellular damage caused by reactive oxygen species (ROS), has been implicated in many diseases, especially age-related disorders, including AMD.…”

Section: Introductionmentioning

confidence: 99%

EGCG protects against UVB-induced apoptosis via oxidative stress and the JNK1/c-Jun pathway in ARPE19 cells

et al. 2011

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Abstract. Ultraviolet B (UVB) radiation is part of the spectrum of light produced by the sun. This form of radiation has been implicated as one of the potential etiological factors causing age-related macular degeneration (AMD). Oxidative injury to the retinal pigment epithelium (RPE) has also been thought to play a key role in AMD. The aim of the present study was to determine the mechanism by which UVB causes damage to the RPE cells, whether it occurs through oxidative stress and the mitogen-activated protein kinase (MAPK) pathway and whether the green tea extract, (-)-epigallocatechin gallate (EGCG), has a protective role. Cell viability assays were used to determine the viability of the cells under different conditions. Cell death caused by apoptosis was determined using fluorescein isothiocyanate conjugated-annexin V/PI labeling, followed by flow cytometry. Intracellular reactive oxygen species (ROS) levels were measured by flow cytometry. Western blot analysis was used to detect UVB-induced MAPK signaling pathways. The findings showed that UVB induced apoptosis, which increased intracellular ROS in ARPE19 cells. Inhibition of c-Jun NH2-terminal kinase (JNK) with a specific inhibitor augmented this apoptosis, and anisomycin (an activator of JNK) attenuated this apoptosis. In addition, UVB decreased the phosphorylation of JNK1 and c-Jun. Finally, EGCG reduced the ROS generation and apoptosis, and also partially blocked the decreased phosphorylation of JNK1 and c-Jun by UVB irradiation. The findings show that UVB irradiation is able to induce apoptosis in ARPE19 cells through oxidative stress, but EGCG treatment attenuates this damage. In this situation, the JNK pathway plays an anti-apoptotic role. The use of selective activators or antioxidants may be useful in reducing the oxidative damage occurring in AMD.

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Section: Introductionmentioning

confidence: 99%

EGCG protects against UVB-induced apoptosis via oxidative stress and the JNK1/c-Jun pathway in ARPE19 cells

et al. 2011

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“…The eye is another directly exposed organ; however, very little is known about the effect of UV exposure on the retina (1). One previous study described the in vitro effect of UV-C irradiation on lens ·-crystallin, a protein thought to play a role in maintaining lens transparency (2), whereas other studies have analyzed signaling pathways associated with corneal epithelial cell and retinal pigment epithelial cell apoptosis (1,2). Components of UV are capable of reaching the human retina, as shown by a structural study of the rat retina exposed to UV.…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, RPE is thought to be the prime early target for age-related macular degeneration (AMD), which involves RPE cell death and atrophy of the photoreceptors (6). Furthermore, RPE cells are also major targets for UV radiation or oxidative stress-induced damage (1,7,8), which is also a major cause of AMD (6). Studies performed in RPE fields used a spontaneously arising human RPE cell line, or ARPE-19, as a cellular model (1,9).…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, RPE cells are also major targets for UV radiation or oxidative stress-induced damage (1,7,8), which is also a major cause of AMD (6). Studies performed in RPE fields used a spontaneously arising human RPE cell line, or ARPE-19, as a cellular model (1,9). ARPE-19 cells exhibit a polarization, capable of tight junction formation (9).…”

Section: Introductionmentioning

confidence: 99%

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MEK/ERK pathway mediates UVB-induced AQP1 downregulation and water permeability impairment in human retinal pigment epithelial cells

Jiang

Cao²,

Lu³

et al. 2009

Int J Mol Med

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Abstract. Aquaporins (AQPs) are a family of 13 small (~30 kDa/monomer), hydrophobic, integral membrane proteins. AQPs are expressed in various epithelial and endothelial cells involved in fluid transport. Here, we demonstrated for the first time that AQP1 is expressed in cultured human retinal pigment epithelial (RPE) cells (ARPE-19 cell line). Ultraviolet radiation (UVB) and H 2 O 2 , two major factors causing RPE cell damage, induced AQP1 downregulation which was mediated by MEK/ERK activation. UV and H 2 O 2 as well as AQP1-specific siRNA knockdown impaired water permeability of ARPE-19 cells. Notably, pretreatment with all-trans retinoic acid attenuated UV-and H 2 O 2 -induced AQP1 downregulation and water permeability impairment. Considering that water permeability is involved in multiple functions of RPE cells such as cellular junction formation, fluid or protein exchange and barrier formation, our data elucidated a novel mechanism through which UV radiation and oxidative stress induce eye cell damage. Our results further support the notion that all-trans retinoic acid might be useful for protection against UV or oxidative stress-induced eye cell damage.

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“…Previous experiments have indicated conflicting results on cell death of RPE cells exposed to oxidative damage. Cai et al (26) reported that RPE cells exposed to TBHP show death by apoptosis under their conditions, whereas Roduit and Schorderet (27) report that RPE cells exposed to UV show cell death by apoptosis. In contrast, Hanus et al (28) found that RPE cells exposed to TBHP primarily die through necrosis.…”

Section: Sulindac Protection Of Rpe Cells Involves Both Mitochondrialmentioning

confidence: 99%

Pharmacological protection of retinal pigmented epithelial cells by sulindac involves PPAR-α

Sur

Kesaraju

Prentice

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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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 . Besides its established antiinflammatory activity, sulindac has previously been shown to protect cardiac tissue against ischemia/reperfusion 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 ischemic 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.preconditioning | oxidative stress | sulindac | retinal pigmented epithelial cells | age-related macular degeneration O xidative damage, resulting from excess production of reactive oxygen species (ROS), has been implicated in the progression of key ocular disorders such as cataracts, glaucoma, and age-related macular degeneration (AMD). Death of retinal pigmented epithelial (RPE) cells has been shown to be an important contributor to AMD pathophysiology. RPE cells are known to be highly metabolically active, and there is strong evidence that the RPE cells are sensitive to oxidative stress (1). It has been reported that the pathophysiology of AMD is due to cumulative oxidative damage to RPE cells resulting from an imbalance between the generation of ROS and the ability of these cells to destroy and/or protect against ROS damage to macromolecules (2, 3). Hence, strategies for protecting RPE cells against oxidative damage may be particularly important in maintaining retinal function and preventing the development or progression of AMD.Sulindac was one of the first nonsteroidal antiinflammatory drugs (NSAIDs) used to treat inflammation. It is a prodrug, composed of R and S epimers, whose NSAID activity is dependent on the reduction of the epimers to sulindac sulfide, the active cyclooxygenase (COX) inhibitor (4). This reduction is catalyzed by two members of the methionine sulfoxide reductase (Msr) family, MsrA and MsrB,...

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MAP kinase pathways in UV-induced apoptosis of retinal pigment epithelium ARPE19 cells

Cited by 97 publications

References 48 publications

EGCG protects against UVB-induced apoptosis via oxidative stress and the JNK1/c-Jun pathway in ARPE19 cells

EGCG protects against UVB-induced apoptosis via oxidative stress and the JNK1/c-Jun pathway in ARPE19 cells

MEK/ERK pathway mediates UVB-induced AQP1 downregulation and water permeability impairment in human retinal pigment epithelial cells

Pharmacological protection of retinal pigmented epithelial cells by sulindac involves PPAR-α

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