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Cultured Human Retinal Pigment Epithelial Cell Injury Induced by Ultraviolet: Potentiation with Subtoxic Intracellular Zinc Depletion
Journal of the Korean Ophthalmological Society ; : 2458-2469, 2000.
Artigo em Coreano | WPRIM | ID: wpr-85539
ABSTRACT
We studied the mechanism and inhibition of cell death by exposure to UV alone or combination of UV exposure and intracellular zinc depletion with TPEN in cultured human retinal pigment epithelial cells (RPE). Cell death was quantified by measuring LDH release from injured cells. RPE were exposed to UV at 253.7 nm for 1~20 minutes.The 2~5 minutes UV exposure was duration-dependently cytotoxic, whereas 1minute exposure was minimally so.And exposure to TPEN induced concentration-dependent cell death at 1~4 micrometer range ;0.5 micrometer TPEN was minimally toxic.Then, cultures were exposed to varying exposure durations of UV in the absence or presence of 0.5 micrometer TPEN.At any point, the presence of TPEN markedly increased UV toxicity.In contrast, cell membrane-impermeable zinc chelator showed no toxicity.On the other hand, addition of a protein synthesis inhibitor or caspase inhibitor was markedly protective.In addition, RPE injury with exposure to combination of UV 1 min and TPEN 0.25 micrometer was accompanied by TUNEL and Hoechst staining positivity indicating that the toxicity is mainly apoptosis.Electron microscopic examinations revealed that nuclear fragmentation occurred even in sublethal UV or TPEN exposure, suggesting that the injury process already began at these condition consistently with the death being apoptosis. The present study has shown that combination of known risk factors may act synergistically to induce ARMD etc.The RPE injury induced by low dose UV and minimal intracellular zinc depletion was inhibited with protein synthesis inhibitor or caspase inhibitor, so these results suggested the possibility of prevention or treatment of RPE dysfunction.
Assuntos

Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Retinaldeído / Zinco / Fatores de Risco / Morte Celular / Apoptose / Marcação In Situ das Extremidades Cortadas / Células Epiteliais / Mãos Tipo de estudo: Estudo de etiologia / Fatores de risco Limite: Humanos Idioma: Coreano Revista: Journal of the Korean Ophthalmological Society Ano de publicação: 2000 Tipo de documento: Artigo

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Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Retinaldeído / Zinco / Fatores de Risco / Morte Celular / Apoptose / Marcação In Situ das Extremidades Cortadas / Células Epiteliais / Mãos Tipo de estudo: Estudo de etiologia / Fatores de risco Limite: Humanos Idioma: Coreano Revista: Journal of the Korean Ophthalmological Society Ano de publicação: 2000 Tipo de documento: Artigo