UV-Induced Signaling Pathways Associated with Corneal Epithelial Cell Apoptosis

Lu, Luo; Wang, Ling; Shell, Beth

doi:10.1167/iovs.03-0591

Cited by 60 publications

(81 citation statements)

References 45 publications

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“…The inhibitory effect of these blockers on JNK signaling pathway is rather specific because there is a good correlation for the blockers to inhibit UV irradiationinduced JNK activation and Kv channel activity. The dose-response curve demonstrates that 4-AP effectively inhibits JNK activity with an IC 50 of ∼170 μM (Wang et al, 1999a;Lu et al, 2003). This IC 50 value is very close to the IC 50 value that is required for 4-AP to block the K + current in patch clamp studies.…”

Section: Uv-induced K + Channel and Jnk Activationsupporting

confidence: 54%

“…For example, we, as well as other researchers, have shown that stimulation of K + channel activity and dramatic loss of intracellular K + can result in apoptosis in the corneal epithelium, neurons, myeloblastic ML-1 cells, and other cell types (Schulz et al, 1996;Eldadah et al, 1997;Yu et al, 1997;Wang et al, 1999aWang et al, ,2003Lu et al, 2003;Trimarchi et al, 2002;Remillard and Yuan, 2004). It seems that there are dual functions of K + channels involving cell proliferation regulated by epidermal growth factor (EGF) (Lu et al, 2001a) and playing a role in mediating cell death induced by UV irradiation (Wang et al, 1999aLu et al, 2003). We found in corneal epithelial cells that K + channel activity is required for growth factor-stimulated activation of extracellularregulated kinase (ERK) (a MAP kinase) limb and proliferation.…”

Section: Introductionmentioning

confidence: 83%

“…To determine whether such an effect is dependent on a rise in Ca 2+ influx, the effect of UV irradiation on JNK activation is determined in a nominally Ca 2+ -free condition by adding 5 mM EGTA in the extracellular medium. It is interesting that UV irradiation has the same effect on JNK activation in the Ca 2+ -free medium in both corneal epithelial and myeloblastic ML-1 cells (Wang et al, 1999a;Lu et al, 2003). However, suppression of K + channel activity with 4-AP prevents the UV irradiation-induced JNK activation under this condition.…”

Section: Independence Of Jnk Activation On Ca 2+ Influxmentioning

confidence: 96%

“…There is accumulating evidence that support the existence of such a crosstalk, including: (1) voltage-gated K + channel activity involved in cell proliferation (Lu et al, 1993;Xu et al, 1996); (2) Kv channel activity regulated by growth factors (Xu et al, 1999;Roderick et al, 2003); and (3) Kv channel activity associated with Src tyrosine kinase (Holmes et al, 1996;Nitabach et al, 2001). More importantly, portions of the MAP kinase signaling pathways, including JNK/SAPK and p38 signaling pathways, mediate UV irradiation-induced corneal epithelial cell apoptosis (Adler et al, 1996;Price et al, 1996;Merienne et al, 2000;Bodero et al, 2003;Lu et al, 2003). Activation of ICE (caspase 1) can affect upstream events in the JNK pathway at the JNK level Lei et al, 1998).…”

Section: Uv-induced K + Channel and Jnk Activationmentioning

confidence: 99%

“…(Soliven et al, 1991;Dubois and Rouzaire-Dubois, 1993;Bright et al, 1994;Duprat et al, 1995;Szabo et al, 1996;Wang et al, 1999a,b;Lu et al, 2003;Gao et al, 2004;Guo et al, 2005). For example, we, as well as other researchers, have shown that stimulation of K + channel activity and dramatic loss of intracellular K + can result in apoptosis in the corneal epithelium, neurons, myeloblastic ML-1 cells, and other cell types (Schulz et al, 1996;Eldadah et al, 1997;Yu et al, 1997;Wang et al, 1999aWang et al, ,2003Lu et al, 2003;Trimarchi et al, 2002;Remillard and Yuan, 2004). It seems that there are dual functions of K + channels involving cell proliferation regulated by epidermal growth factor (EGF) (Lu et al, 2001a) and playing a role in mediating cell death induced by UV irradiation (Wang et al, 1999aLu et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Stress-induced corneal epithelial apoptosis mediated by K+ channel activation

2006

Progress in Retinal and Eye Research

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One of the functional roles of the corneal epithelial layer is to protect the cornea, lens and other underlying ocular structures from damages caused by environmental insults. It is important for corneal epithelial cells to maintain this function by undergoing continuous renewal through a dynamic process of wound healing. Previous studies in corneal epithelial cells have provided substantial evidence showing that environmental insults, such as ultraviolet (UV) irradiation and other biohazards, can induce stress-related cellular responses resulting in apoptosis and thus interrupt the dynamic process of wound healing. We found that UV irradiation-induced apoptotic effects in corneal epithelial cells are started by the hyperactivation of K + channels in the cell membrane resulting in a fast loss of intracellular K + ions. Recent studies provide further evidence indicating that these complex responses in corneal epithelial cells are resulted from the activation of stressrelated signaling pathways mediated by K + channel activity. The effect of UV irradiation on corneal epithelial cell fate shares common signaling mechanisms involving the activation of intracellular responses that are often activated by the stimulation of various cytokines. One piece of evidence for making this distinction is that at early times UV irradiation activates a Kv3.4 channel in corneal epithelial cells to elicit activation of c-Jun N-terminal kinase cascades and p53 activation leading to cell cycle arrest and apoptosis. The hypothetic model is that UV-induced potassium channel hyperactivity as an early event initiates fast cell shrinkages due to the loss of intracellular potassium, resulting in the activation of scaffolding protein kinases and cytoskeleton reorganizations. This review article presents important control mechanisms that determine Kv channel activity-mediated cellular responses in corneal epithelial cells, involving activation of stress-induced signaling pathways, arrests of cell cycle progression and/or induction of apoptosis.

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Section: Uv-induced K + Channel and Jnk Activationsupporting

confidence: 54%

Section: Introductionmentioning

confidence: 83%

Section: Independence Of Jnk Activation On Ca 2+ Influxmentioning

confidence: 96%

Section: Uv-induced K + Channel and Jnk Activationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Stress-induced corneal epithelial apoptosis mediated by K+ channel activation

2006

Progress in Retinal and Eye Research

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Arsenite pre‐conditioning reduces UVB‐induced apoptosis in corneal epithelial cells through the anti‐apoptotic activity of 27 kDa heat shock protein (HSP27)

Shi

Isseroff

2005

Journal Cellular Physiology

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Exposure to ultraviolet (UV) light poses a health risk for eye disease, and solar ultraviolet in the B range (UVB, 280-320 nm) is known to be related to various corneal disorders. In this study, we investigated whether pre-conditioning of cells with arsenite (AsO2(-1)) can reduce UVB-induced apoptosis in human corneal epithelial cells, and whether the anti-apoptotic activity of 27 kDa heat shock protein (HSP27), a small heat shock protein, plays a role in this protection. UVB at levels comparable to physiologic solar exposure induces apoptosis of corneal epithelial cells in culture, demonstrated by activation of caspase 9 and caspase 3, and DNA fragmentation. When cells were pre-conditioned with arsenite prior to UVB exposure, the UVB-induced cell death was reduced, and UVB-induced activation of caspases and DNA fragmentation was inhibited. When cells were pre-treated with SB 203580, which inhibits HSP27 phosphorylation through inhibition of p38 MAP kinase activation, the arsenite-induced reduction of UVB-induced apoptosis was partially reversed. Arsenite pre-conditioning inhibited UVB-induced apoptosis in a two-phase pattern, which was temporally correlated with arsenite-induced HSP27 expression and phosphorylation. Neutralization of intracellular HSP27 with its antibody reduced arsenite's inhibition of UVB-induced caspase3 activation. Our results suggest that forms of stress that upregulate HSP27 and its phosphorylation may be useful as novel approaches to prevent adverse ocular effects arising from UV exposure in humans.

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Up‐regulation of heat shock protein 70‐1 (Hsp70‐1) in human limbo‐corneal epithelial cells cultivated on amniotic membrane: A proteomic study

Hui‐Kang

Lai

et al. 2012

Journal Cellular Physiology

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Transplantation of cultivated human limbo-corneal epithelial (HLE) cells has been recognized as an effective stem cell (SC) therapy for treating corneal epithelial SC deficiency caused by burn or other diseases. With this technique, cryo-preserved human intact amniotic membrane (IAM) has been successfully used as a cell culture substrate and carrier, and is reported to preferentially preserve HLE stem/progenitor cells in vitro. However, little is known about what factors released by HLE cells are involved in the progenitor cell-preserving mechanism. Using proteomic method, we identified 13 proteins over-expressed by HLE cells cultured on IAM, which included heat shock protein 70-1 (Hsp70-1), Hsp-27, glutathione (GSH) S-transferase, annexin A2, galectin-7, and protein S100-A9. Increased Hsp70-1 expression was confirmed by Western blot and real-time PCR. The role of Hsp70-1 in promoting HLE cell survival was demonstrated by increased apoptosis index and increased cleaved poly ADP-ribose polymerase (CPARP) formation in hsp70-1-silenced, but not normal HLE cells after exposure to sublethal UVB irradiation or hydrogen peroxide. To understand the regulatory mechanism of Hsp70-1 expression in HLE cells, the role of transcription factor deltaNp63 (a well-recognized HLE stem cell; SC marker) was studied. We found that over-expression of deltaNp63α by plasmid vector induced a corresponding increase in Hsp70-1 protein production. Likewise, Hsp70-1 expression decreased in HLE cells after addition of deltaNp63α SiRNA. Immunoconfocal microscopy also revealed a paralleled expression of both proteins in corneal specimens. Thus, deltaNp63α-associated Hsp70-1 over-expression may promote HLE progenitor cell survival on IAM, possibly through the cytoprotective and anti-apoptotic effect of Hsp70-1.

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UV-Induced Signaling Pathways Associated with Corneal Epithelial Cell Apoptosis

Abstract: UV-irradiation-induced corneal epithelial cell apoptosis is mediated through activation of the SEK/JNK signaling pathway. Such activation is dependent on increases in K+ channel activity, which play an important role in the early events that result in activation of this pathway.

Cited by 60 publications

References 45 publications

Stress-induced corneal epithelial apoptosis mediated by K+ channel activation

Stress-induced corneal epithelial apoptosis mediated by K+ channel activation

Arsenite pre‐conditioning reduces UVB‐induced apoptosis in corneal epithelial cells through the anti‐apoptotic activity of 27 kDa heat shock protein (HSP27)

Up‐regulation of heat shock protein 70‐1 (Hsp70‐1) in human limbo‐corneal epithelial cells cultivated on amniotic membrane: A proteomic study

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