Sphingosine Kinase 2 Phosphorylation of FTY720 is Unnecessary for Prevention of Light-Induced Retinal Damage
Year: 2019
Type: article
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.
Source: Scientific Reports
Authors: 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
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,790
Awards: Sphingolipid Metabolism and Signaling in the Retina, G1525133475, Sphingolipid signaling in corneal wound healing and fibrosis, G2858254377, G3197302258, G46069158, G46402933, G536928286, G5514841323, G6941695240, G9000090571, G9000115301, G9000186613, P30 Center Core Grant for Vision Research, Massey Cancer Center - Cancer Center Support Grant
OpenAlex ID: W2945775448