Synergistic Protection of N-Acetylcysteine and Ascorbic Acid 2-Phosphate on Human Mesenchymal Stem cells Against Mitoptosis, Necroptosis and Apoptosis

Synergistic Protection of N-Acetylcysteine and Ascorbic Acid 2-Phosphate on Human Mesenchymal Stem cells Against Mitoptosis, Necroptosis and Apoptosis

Human mesenchymal stem cells (hMSCs) contribute to ischemic tissue repair, regeneration, and possess ability to self-renew. However, poor viability of transplanted hMSCs within ischemic tissues has limited its therapeutic efficiency. Therefore, it is urgent to explore new method to improve the viabi...

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Main Authors: Li, Chia-Jung, Sun, Li-Yi, Pang, Cheng-Yoong
Format: Online
Language:English
Published: Nature Publishing Group 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408980/
id pubmed-4408980
recordtype oai_dc
spelling pubmed-44089802015-05-08 Synergistic Protection of N-Acetylcysteine and Ascorbic Acid 2-Phosphate on Human Mesenchymal Stem cells Against Mitoptosis, Necroptosis and Apoptosis Li, Chia-Jung Sun, Li-Yi Pang, Cheng-Yoong Article Human mesenchymal stem cells (hMSCs) contribute to ischemic tissue repair, regeneration, and possess ability to self-renew. However, poor viability of transplanted hMSCs within ischemic tissues has limited its therapeutic efficiency. Therefore, it is urgent to explore new method to improve the viability of the grafted cells. By using a systematic analysis, we reveal the mechanism of synergistic protection of N-acetylcysteine (NAC) and ascorbic acid 2-phosphate (AAP) on hMSCs that were under H2O2-induced oxidative stress. The combined treatment of NAC and AAP (NAC/AAP) reduces reactive oxygen species (ROS) generation, stabilizes mitochondrial membrane potential and decreases mitochondrial fission/fragmentation due to oxidative stress. Mitochondrial fission/fragmentation is a major prologue of mitoptosis. NAC/AAP prevents apoptotic cell death via decreasing the activation of BAX, increasing the expression of BCL2, and reducing cytochrome c release from mitochondria that might lead to the activation of caspase cascade. Stabilization of mitochondria also prevents the release of AIF, and its nuclear translocation which may activate necroptosis via H2AX pathway. The decreasing of mitoptosis is further studied by MicroP image analysis, and is associated with decreased activation of Drp1. In conclusion, NAC/AAP protects mitochondria from H2O2-induced oxidative stress and rescues hMSCs from mitoptosis, necroptosis and apoptosis. Nature Publishing Group 2015-04-24 /pmc/articles/PMC4408980/ /pubmed/25909282 http://dx.doi.org/10.1038/srep09819 Text en Copyright © 2015, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Li, Chia-Jung
Sun, Li-Yi
Pang, Cheng-Yoong
spellingShingle Li, Chia-Jung
Sun, Li-Yi
Pang, Cheng-Yoong
Synergistic Protection of N-Acetylcysteine and Ascorbic Acid 2-Phosphate on Human Mesenchymal Stem cells Against Mitoptosis, Necroptosis and Apoptosis
author_facet Li, Chia-Jung
Sun, Li-Yi
Pang, Cheng-Yoong
author_sort Li, Chia-Jung
title Synergistic Protection of N-Acetylcysteine and Ascorbic Acid 2-Phosphate on Human Mesenchymal Stem cells Against Mitoptosis, Necroptosis and Apoptosis
title_short Synergistic Protection of N-Acetylcysteine and Ascorbic Acid 2-Phosphate on Human Mesenchymal Stem cells Against Mitoptosis, Necroptosis and Apoptosis
title_full Synergistic Protection of N-Acetylcysteine and Ascorbic Acid 2-Phosphate on Human Mesenchymal Stem cells Against Mitoptosis, Necroptosis and Apoptosis
title_fullStr Synergistic Protection of N-Acetylcysteine and Ascorbic Acid 2-Phosphate on Human Mesenchymal Stem cells Against Mitoptosis, Necroptosis and Apoptosis
title_full_unstemmed Synergistic Protection of N-Acetylcysteine and Ascorbic Acid 2-Phosphate on Human Mesenchymal Stem cells Against Mitoptosis, Necroptosis and Apoptosis
title_sort synergistic protection of n-acetylcysteine and ascorbic acid 2-phosphate on human mesenchymal stem cells against mitoptosis, necroptosis and apoptosis
description Human mesenchymal stem cells (hMSCs) contribute to ischemic tissue repair, regeneration, and possess ability to self-renew. However, poor viability of transplanted hMSCs within ischemic tissues has limited its therapeutic efficiency. Therefore, it is urgent to explore new method to improve the viability of the grafted cells. By using a systematic analysis, we reveal the mechanism of synergistic protection of N-acetylcysteine (NAC) and ascorbic acid 2-phosphate (AAP) on hMSCs that were under H2O2-induced oxidative stress. The combined treatment of NAC and AAP (NAC/AAP) reduces reactive oxygen species (ROS) generation, stabilizes mitochondrial membrane potential and decreases mitochondrial fission/fragmentation due to oxidative stress. Mitochondrial fission/fragmentation is a major prologue of mitoptosis. NAC/AAP prevents apoptotic cell death via decreasing the activation of BAX, increasing the expression of BCL2, and reducing cytochrome c release from mitochondria that might lead to the activation of caspase cascade. Stabilization of mitochondria also prevents the release of AIF, and its nuclear translocation which may activate necroptosis via H2AX pathway. The decreasing of mitoptosis is further studied by MicroP image analysis, and is associated with decreased activation of Drp1. In conclusion, NAC/AAP protects mitochondria from H2O2-induced oxidative stress and rescues hMSCs from mitoptosis, necroptosis and apoptosis.
publisher Nature Publishing Group
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408980/
_version_ 1613215404573851648

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