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Characterizing the protective effects of SHLP2, a mitochondrial-derived peptide, in macular degeneration

Mitochondrial-derived peptides (MDPs) are rapidly emerging therapeutic targets to combat development of neurodegenerative diseases. SHLP2 (small humanin-like peptide 2) is a newly discovered MDP that is coded from the MT-RNR2 (Mitochondrially encoded 16S rRNA) gene in mitochondrial DNA (mtDNA). In t...

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Autores principales: Nashine, Sonali, Cohen, Pinchas, Nesburn, Anthony B., Kuppermann, Baruch D., Kenney, M. Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182005/
https://www.ncbi.nlm.nih.gov/pubmed/30310092
http://dx.doi.org/10.1038/s41598-018-33290-5
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author Nashine, Sonali
Cohen, Pinchas
Nesburn, Anthony B.
Kuppermann, Baruch D.
Kenney, M. Cristina
author_facet Nashine, Sonali
Cohen, Pinchas
Nesburn, Anthony B.
Kuppermann, Baruch D.
Kenney, M. Cristina
author_sort Nashine, Sonali
collection PubMed
description Mitochondrial-derived peptides (MDPs) are rapidly emerging therapeutic targets to combat development of neurodegenerative diseases. SHLP2 (small humanin-like peptide 2) is a newly discovered MDP that is coded from the MT-RNR2 (Mitochondrially encoded 16S rRNA) gene in mitochondrial DNA (mtDNA). In the current study, we examined the biological consequences of treatment with exogenously-added SHLP2 in an in vitro human transmitochondrial age-related macular degeneration (AMD) ARPE-19 cell model. In AMD cells, we observed significant down-regulation of the MDP-coding MT-RNR2 gene, and remarkably reduced levels of all five oxidative phosphorylation (OXPHOS) complex I-V protein subunits that are involved in the electron transport chain; these results suggested mitochondrial toxicity and abnormal OXPHOS complex protein subunits’ levels in AMD cells. However, treatment of AMD cells with SHLP2: (1) restored the normal levels of OXPHOS complex protein subunits, (2) prevented loss of viable cells and mitochondria, (3) increased the number of mtDNA copies, (4) induced anti-apoptotic effects, and (5) attenuated amyloid-β-induced cellular and mitochondrial toxicity. Cumulatively, our findings established the protective role of SHLP2 in AMD cells in vitro. In conclusion, this novel study supports the merit of SHLP2 in the treatment of AMD, a primary retinal disease that is a leading cause of blindness among the elderly population in the United States as well as worldwide.
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spelling pubmed-61820052018-10-15 Characterizing the protective effects of SHLP2, a mitochondrial-derived peptide, in macular degeneration Nashine, Sonali Cohen, Pinchas Nesburn, Anthony B. Kuppermann, Baruch D. Kenney, M. Cristina Sci Rep Article Mitochondrial-derived peptides (MDPs) are rapidly emerging therapeutic targets to combat development of neurodegenerative diseases. SHLP2 (small humanin-like peptide 2) is a newly discovered MDP that is coded from the MT-RNR2 (Mitochondrially encoded 16S rRNA) gene in mitochondrial DNA (mtDNA). In the current study, we examined the biological consequences of treatment with exogenously-added SHLP2 in an in vitro human transmitochondrial age-related macular degeneration (AMD) ARPE-19 cell model. In AMD cells, we observed significant down-regulation of the MDP-coding MT-RNR2 gene, and remarkably reduced levels of all five oxidative phosphorylation (OXPHOS) complex I-V protein subunits that are involved in the electron transport chain; these results suggested mitochondrial toxicity and abnormal OXPHOS complex protein subunits’ levels in AMD cells. However, treatment of AMD cells with SHLP2: (1) restored the normal levels of OXPHOS complex protein subunits, (2) prevented loss of viable cells and mitochondria, (3) increased the number of mtDNA copies, (4) induced anti-apoptotic effects, and (5) attenuated amyloid-β-induced cellular and mitochondrial toxicity. Cumulatively, our findings established the protective role of SHLP2 in AMD cells in vitro. In conclusion, this novel study supports the merit of SHLP2 in the treatment of AMD, a primary retinal disease that is a leading cause of blindness among the elderly population in the United States as well as worldwide. Nature Publishing Group UK 2018-10-11 /pmc/articles/PMC6182005/ /pubmed/30310092 http://dx.doi.org/10.1038/s41598-018-33290-5 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Nashine, Sonali
Cohen, Pinchas
Nesburn, Anthony B.
Kuppermann, Baruch D.
Kenney, M. Cristina
Characterizing the protective effects of SHLP2, a mitochondrial-derived peptide, in macular degeneration
title Characterizing the protective effects of SHLP2, a mitochondrial-derived peptide, in macular degeneration
title_full Characterizing the protective effects of SHLP2, a mitochondrial-derived peptide, in macular degeneration
title_fullStr Characterizing the protective effects of SHLP2, a mitochondrial-derived peptide, in macular degeneration
title_full_unstemmed Characterizing the protective effects of SHLP2, a mitochondrial-derived peptide, in macular degeneration
title_short Characterizing the protective effects of SHLP2, a mitochondrial-derived peptide, in macular degeneration
title_sort characterizing the protective effects of shlp2, a mitochondrial-derived peptide, in macular degeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182005/
https://www.ncbi.nlm.nih.gov/pubmed/30310092
http://dx.doi.org/10.1038/s41598-018-33290-5
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