All-trans-retinoic acid generation is an antidotal clearance pathway for all-trans-retinal in the retina.

All-trans-retinoic acid generation is an antidotal clearance pathway for all-trans-retinal in the retina.
J Zhejiang Univ Sci B. 2019 Dec.;20(12):960-971
Authors: Xia QQ, Zhang LM, Zhou YY, Wu YL, Li J
Abstract
The present study was designed to analyze the metabolites of all-trans-retinal (atRal) and compare the cytotoxicity of atRal versus its derivative all-trans-retinoic acid (atRA) in human retinal pigment epithelial (RPE) cells. We confirmed that atRA was produced in normal pig neural retina and RPE. The amount of all-trans-retinol (atROL) converted from atRal was about 2.7 times that of atRal-derived atRA after incubating RPE cells with 10 μmol/L atRal for 24 h, whereas atRA in medium supernatant is more plentiful (91 vs. 29 pmol/mL), suggesting that atRA conversion facilitates elimination of excess atRal in the retina. Moreover, we found that mRNA expression of retinoic acid-specific hydroxylase CYP26b1 was dose-dependently up-regulated by atRal exposure in RPE cells, indicating that atRA inactivation may be also initiated in atRal-accumulated RPE cells. Our data show that atRA-caused viability inhibition was evidently reduced compared with the equal concentration of its precursor atRal. Excess accumulation of atRal provoked intracellular reactive oxygen species (ROS) overproduction, heme oxygenase-1 (HO-1) expression, and increased cleaved poly(ADP-ribose) polymerase 1 (PARP1) expression in RPE cells. In contrast, comparable...

Source: J Zhejiang Univ Sci ... - November 23, 2019 Category: Science Authors: Xia QQ, Zhang LM, Zhou YY, Wu YL, Li J Tags: J Zhejiang Univ Sci B Source Type: research