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Blue light‐excited retinal delocalizes plasma membrane bound PIP2 and triggers stress responses challenging the cellular integrity
Author(s) -
Ratnayake Kasun,
Payton John L.,
Karunarathne Ajith
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.533.36
Subject(s) - retinal , retinaldehyde , biophysics , chemistry , retina , phototoxicity , chromophore , retinal degeneration , rhodopsin , photochemistry , biochemistry , biology , neuroscience , in vitro
The photoreceptor chromophore, retinal, an aldehyde derivative of vitamin A, harvests light to generate visual perception. Upon photon absorption, the receptor bound 11‐cis‐retinylidene (11CR) isomerizes to all trans retinal (ATR), changing the electrostatic environment in the chromophore‐binding site, subsequently transforming the inactive receptor to a momentary active state. The subsequent release of ATR allows the receptor to be relaxed to the basal state, enables a new 11CR binding and continuous photon reception. Due to the defects in retinal clearance mechanisms, higher concentrations of 11CR and ATR can be found in the retina, and a fraction of excess retinal can enter the circulation, exposing the rest of the body to retinal as well, leading to pathophysiological effects. Nevertheless, visible light induced, photoreceptor independent signaling activities of retinals and mechanisms of retinal phototoxicity are less explored. Here, we show that, retinal, in the presence of blue light, irreversibly remove the plasma membrane (PM) bound phosphatidylinositol 4,5 bisphosphate (PIP2) in photoreceptor and non‐photoreceptor cells. Interestingly, addition of retinals alone without blue light exposure as well as exposing cells to only blue light without retinal, did not show any detectable PIP2 dislodging from PM. Additionally, even in the presence of retinal, the other wavelengths of lights failed to show any effect on PM bound PIP2. Moreover, compounds that are structurally similar to retinal such as retinol and retinoic acid did not show any effect on PIP2 in the presence of blue light. Data further show that, this PIP2 removal from the PM is not due to regular enzymatic hydrolysis of PIP2, but as a result of lipid peroxidation induced by the generation of singlet oxygen and reactive oxygen species. The resultant PIP2 dislodging is followed by cellular stress responses and cell death. Clinically used photodynamic therapeutic agents (photosensitizers), also showed a unique PIP2 dislodging effect from PM in the presence of blue light as well as in other wavelengths of light, similar to blue light excited retinal. This further confirms retinal's ability to harvest light to induce photosensitization that leads to lipid peroxidation which suggests its future potential in photodynamic therapeutics in cancer as well as identification of new molecular targets for phototoxicity. Overall, here we show that, retinal exhibit light sensitivity in non‐photoreceptor cells and trigger crucial signaling pathways altering the cellular fate. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .