Neuroprotection of retinal cells by Caffeic Acid Phenylethyl Ester(CAPE) is mediated by mitochondrial uncoupling protein UCP2

Mingliang Zhang, Liming Wang, Dejia Wen, Changjie Ren, Shuang Chen, Zhihui Zhang, Lanlan Hu, Zihao Yu, Joyce Tombran-Tink, Xiaomin Zhang, Xiaorong Li, Colin J. Barnstable

Research output: Contribution to journalArticlepeer-review

Abstract

Oxidative stress due to mitochondrial produced reactive oxygen species is a major cause of damage seen in many retinal degenerative diseases. Caffeic acid phenylethyl ester (CAPE) is protective agent in multiple tissues and is reported to have anti-oxidant properties. Systemically applied CAPE protected retinal ganglion cells from ischemic injury induced by increased intraocular pressure. CAPE provided complete protection for ARPE19 retinal pigment epithelial cells against tert-butyl hydrogen peroxide and reduced both basal and LPS-stimulated ROS production. The major effect of CAPE was mediated by the mitochondrial uncoupling protein UCP2 since both pharmacological inhibition of UCP2 and siRNA-induced knockdown removed the ability of CAPE to block ROS production. Based on common structural features, CAPE may be acting as a mimetic of the natural UCP2 homeostatic regulator 4-hydroxy-2-nonenal. CAPE may provide a valuable tool to treat oxidative stress-related damage in retinal and other degenerative diseases.

Original languageEnglish (US)
Article number105214
JournalNeurochemistry International
Volume151
DOIs
StatePublished - Dec 2021

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this