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Neurochem Res. 2016 Sep;41(9):2324-35. doi: 10.1007/s11064-016-1946-5. Epub 2016 May 23.

Blue Light Action on Mitochondria Leads to Cell Death by Necroptosis.

Author information

1
Fundación de Investigación Oftalmológica, Avda. Doctores Fernández-Vega 34, 33012, Oviedo, Asturias, Spain.
2
Fundación de Investigación Oftalmológica, Avda. Doctores Fernández-Vega 34, 33012, Oviedo, Asturias, Spain. Neville.osborne@eye.ox.ac.uk.

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.

KEYWORDS:

Apoptosis-inducing factor (AIF); Blue light; Heme-oxygenase-1 (HO-1); Mitochondria; Necroptosis; Protein kinase-1 (RIP1) and 3 (RIP3)

PMID:
27216620
DOI:
10.1007/s11064-016-1946-5
[Indexed for MEDLINE]

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