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Blue Light Action on Mitochondria Leads to Cell Death by Necroptosis

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Abstract

Blue light impinging on the many mitochondria associated with retinal ganglion cells (RGCs) in situ has the potential of eliciting necroptosis through an action on RIP1/RIP3 to stimulate RGC death in diseases like glaucoma and diabetic retinopathy. Cells in culture die when exposed to blue light. The death process is mitochondria-dependent and is known to involve a decrease in the production of ATP, a generation of ROS, the activation of poly-(ADP-ribose) polymerase, the stimulation of apoptosis-inducing factor (AIF) as well as the up-regulation of heme-oxygenase-1 (HO-1). Our present results show that blue light-induced activation of AIF is not directly linked with the stimulation of RIP1/RIP3. Down-regulation of RIP1/RIP3 did not influence AIF. AIF activation therefore appears to enhance the rate of necroptosis by a direct action on DNA breakdown, the end stage of necroptosis. This implies that silencing of AIF mRNA may provide a degree of protection to blue light insult. Also, necrostatin-1 attenuated an increased turnover of HO-1 mRNA caused by blue light to suggest an indirect inhibition of necroptosis, caused by the action of necrostatin-1 on RIP1/RIP3 to reduce oxidative stress. This is supported by the finding that gene silencing of RIP1 and RIP3 has no effect on HO-1. We therefore conclude that inhibitors of RIP kinase might be more specific than necrostatin-1 as a neuroprotective agent to blunt solely necroptosis caused by blue light.

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Acknowledgments

We gratefully acknowledge the financial support from the Fundación BBVA and the technical assistance of Enol Artime. Financial support is gratefully acknowledged from the Fundación BBVA and the Fundación Endesa. NNO and is a Cátedra de Biomedicina (Chair in Biomedicine).

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Authors and Affiliations

  1. Fundación de Investigación Oftalmológica, Avda. Doctores Fernández-Vega 34, 33012, Oviedo, Asturias, Spain

    Susana del Olmo-Aguado, Claudia Núñez-Álvarez & Neville N. Osborne

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  1. Susana del Olmo-Aguado
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  2. Claudia Núñez-Álvarez
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  3. Neville N. Osborne
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Correspondence to Neville N. Osborne.

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del Olmo-Aguado, S., Núñez-Álvarez, C. & Osborne, N.N. Blue Light Action on Mitochondria Leads to Cell Death by Necroptosis. Neurochem Res 41, 2324–2335 (2016). https://doi.org/10.1007/s11064-016-1946-5

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  • DOI: https://doi.org/10.1007/s11064-016-1946-5

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