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Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 1675230, 11 pages
https://doi.org/10.1155/2017/1675230
Review Article

Protective Mechanisms of the Mitochondrial-Derived Peptide Humanin in Oxidative and Endoplasmic Reticulum Stress in RPE Cells

1Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA
2Arnold and Mabel Beckman Macular Research Center, Doheny Eye Institute, Los Angeles, CA, USA
3Department Ophthalmology, USC Roski Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA

Correspondence should be addressed to Ram Kannan; gro.ynehod@nannakr

Received 13 March 2017; Revised 13 June 2017; Accepted 28 June 2017; Published 26 July 2017

Academic Editor: Luciano Saso

Copyright © 2017 Leonid Minasyan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Age-related macular degeneration (AMD) is the leading cause of severe and irreversible vision loss and is characterized by progressive degeneration of the retina resulting in loss of central vision. The retinal pigment epithelium (RPE) is a critical site of pathology of AMD. Mitochondria and the endoplasmic reticulum which lie in close anatomic proximity to each other are targets of oxidative stress and endoplasmic reticulum (ER) stress, respectively, and contribute to the progression of AMD. The two organelles exhibit close interactive function via various signaling mechanisms. Evidence for ER-mitochondrial crosstalk in RPE under ER stress and signaling pathways of apoptotic cell death is presented. The role of humanin (HN), a prominent member of a newly discovered family of mitochondrial-derived peptides (MDPs) expressed from an open reading frame of mitochondrial 16S rRNA, in modulation of ER and oxidative stress in RPE is discussed. HN protected RPE cells from oxidative and ER stress-induced cell death by upregulation of mitochondrial GSH, inhibition of ROS generation, and caspase 3 and 4 activation. The underlying mechanisms of ER-mitochondrial crosstalk and modulation by exogenous HN are discussed. The therapeutic use of HN and related MDPs could potentially prove to be a valuable approach for treatment of AMD.