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CLC number: R777.1

On-line Access: 2019-11-21

Received: 2019-05-27

Revision Accepted: 2019-08-31

Crosschecked: 2019-10-08

Cited: 0

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Citations:  Bibtex RefMan EndNote GB/T7714


Jie Li


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Journal of Zhejiang University SCIENCE B 2019 Vol.20 No.12 P.960-971


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

Author(s):  Qing-Qing Xia, Ling-Min Zhang, Ying-Ying Zhou, Ya-Lin Wu, Jie Li

Affiliation(s):  Central Laboratory, Department of Laboratory Medicine, Huangyan Hospital of Wenzhou Medical University, Taizhou First People’s Hospital, Taizhou 318020, China; more

Corresponding email(s):   yalinw@xmu.edu.cn, liyijie12580@126.com

Key Words:  All-trans-retinal, All-trans-retinoic acid, Antidotal pathway, Human retinal pigment epithelial cell, Oxidative stress

Qing-Qing Xia, Ling-Min Zhang, Ying-Ying Zhou, Ya-Lin Wu, Jie Li. All-trans-retinoic acid generation is an antidotal clearance pathway for all-trans-retinal in the retina[J]. Journal of Zhejiang University Science B, 2019, 20(12): 960-971.

@article{title="All-trans-retinoic acid generation is an antidotal clearance pathway for all-trans-retinal in the retina",
author="Qing-Qing Xia, Ling-Min Zhang, Ying-Ying Zhou, Ya-Lin Wu, Jie Li",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T All-trans-retinoic acid generation is an antidotal clearance pathway for all-trans-retinal in the retina
%A Qing-Qing Xia
%A Ling-Min Zhang
%A Ying-Ying Zhou
%A Ya-Lin Wu
%A Jie Li
%J Journal of Zhejiang University SCIENCE B
%V 20
%N 12
%P 960-971
%@ 1673-1581
%D 2019
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1900271

T1 - All-trans-retinoic acid generation is an antidotal clearance pathway for all-trans-retinal in the retina
A1 - Qing-Qing Xia
A1 - Ling-Min Zhang
A1 - Ying-Ying Zhou
A1 - Ya-Lin Wu
A1 - Jie Li
J0 - Journal of Zhejiang University Science B
VL - 20
IS - 12
SP - 960
EP - 971
%@ 1673-1581
Y1 - 2019
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1900271

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 dosage of atRA-induced oxidative stress was much weaker, and it could not activate apoptosis in RPE cells. These results suggest that atRA generation is an antidotal metabolism pathway for atRal in the retina. Moreover, we found that in the eyes of ABCA4−/−RDH8−/− mice, a mouse model with atRal accumulation in the retina, the atRA content was almost the same as that in the wild type. It is possible that atRal accumulation simultaneously and equally promotes atRA synthesis and clearance in eyes of ABCA4−/−RDH8−/− mice, thus inhibiting the further increase of atRA in the retina. Our present study provides further insights into atRal clearance in the retina.


方法:利用UPLC-MS/MS分别检测猪眼神经视网膜及RPE层中atRA的含量;利用ARPE-19细胞系模拟atRal在RPE中累积,用UPLC-MS/MS检测细胞内及培养基中atRA的含量,并用定量聚合酶链反应(qPCR)检测CYP26b1的表达;利用CCK8、DCFH-DA染色、qPCR、western blot等方法对比等浓度atRA和atRal在RPE细胞中所诱 导的细胞毒性、氧化应激、凋亡相关蛋白表达水平;用UPLC-MS/MS检测视网膜atRal清除障碍的ABCA4−/−RDH8−/−小鼠眼球中atRA及全反式视黄醇.


Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


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