Sphingosine Kinase 2 Phosphorylation of FTY720 is Unnecessary for Prevention of Light-Induced Retinal Damage

Hui Qi, Jerome Cole, Richard C. Grambergs, John R. Gillenwater, Koushik Mondal, Sufiya Khanam, Soma Dutta, Megan Stiles, Richard L. Proia, Jeremy Allegood, Nawajes Mandal

Research output: Contribution to journalArticle

Abstract

Mammalian Sphingosine kinase 2 is the primary enzyme responsible for phosphorylating FTY720 to its active form, FTY720-P. Systemic FTY720 treatment confers significant protection to murine retinas from light- and disease-mediated photoreceptor cell death. It is not clear whether FTY720-P, FTY720, or both are responsible for this photoreceptor protection. We investigated Sphingosine kinase 2 knockout (Sphk2 KO) mouse retinas, tested their sensitivity to light, and measured what degree of protection from light-induced damage they receive from systemic FTY720 treatment. Sphk2 KO retinas were found to be similar to their wild-type counterparts in sensitivity to light damage. Additionally, FTY720 treatment protected Sphk2 KO retinas from light-induced damage despite significant retardation of FTY720 phosphorylation in Sphk2 KO mice. We conclude that FTY720 serves an active role in preventing photoreceptor cell death. Furthermore, we conclude that the phosphorylation of FTY720 is not necessary to provide this protective effect.

Original languageEnglish (US)
Article number7771
JournalScientific Reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Phosphorylation
Light
Retina
Photophobia
Photoreceptor Cells
Knockout Mice
Cell Death
sphingosine kinase
Fingolimod Hydrochloride
Enzymes

All Science Journal Classification (ASJC) codes

  • General

Cite this

Sphingosine Kinase 2 Phosphorylation of FTY720 is Unnecessary for Prevention of Light-Induced Retinal Damage. / Qi, Hui; Cole, Jerome; Grambergs, Richard C.; Gillenwater, John R.; Mondal, Koushik; Khanam, Sufiya; Dutta, Soma; Stiles, Megan; Proia, Richard L.; Allegood, Jeremy; Mandal, Nawajes.

In: Scientific Reports, Vol. 9, No. 1, 7771, 01.12.2019.

Research output: Contribution to journalArticle

Qi, H, Cole, J, Grambergs, RC, Gillenwater, JR, Mondal, K, Khanam, S, Dutta, S, Stiles, M, Proia, RL, Allegood, J & Mandal, N 2019, 'Sphingosine Kinase 2 Phosphorylation of FTY720 is Unnecessary for Prevention of Light-Induced Retinal Damage', Scientific Reports, vol. 9, no. 1, 7771. https://doi.org/10.1038/s41598-019-44047-z
Qi, Hui ; Cole, Jerome ; Grambergs, Richard C. ; Gillenwater, John R. ; Mondal, Koushik ; Khanam, Sufiya ; Dutta, Soma ; Stiles, Megan ; Proia, Richard L. ; Allegood, Jeremy ; Mandal, Nawajes. / Sphingosine Kinase 2 Phosphorylation of FTY720 is Unnecessary for Prevention of Light-Induced Retinal Damage. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
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abstract = "Mammalian Sphingosine kinase 2 is the primary enzyme responsible for phosphorylating FTY720 to its active form, FTY720-P. Systemic FTY720 treatment confers significant protection to murine retinas from light- and disease-mediated photoreceptor cell death. It is not clear whether FTY720-P, FTY720, or both are responsible for this photoreceptor protection. We investigated Sphingosine kinase 2 knockout (Sphk2 KO) mouse retinas, tested their sensitivity to light, and measured what degree of protection from light-induced damage they receive from systemic FTY720 treatment. Sphk2 KO retinas were found to be similar to their wild-type counterparts in sensitivity to light damage. Additionally, FTY720 treatment protected Sphk2 KO retinas from light-induced damage despite significant retardation of FTY720 phosphorylation in Sphk2 KO mice. We conclude that FTY720 serves an active role in preventing photoreceptor cell death. Furthermore, we conclude that the phosphorylation of FTY720 is not necessary to provide this protective effect.",
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