Grape seed proanthocyanidin extract protects lymphocytes against histone-induced apoptosis

Apoptosis of lymphocytes is associated with immunosuppression and poor prognosis in sepsis. Our previous report showed that histones, nuclear proteins released from damaged or dying cells in sepsis, can mediate lymphocyte apoptosis via mitochondria damage. Grape seed proanthocyanidin extract (GSPE),...

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Main Authors: Ping Chang, Bing Mo, David M. Cauvi, Ying Yu, Zhenhui Guo, Jian Zhou, Qiong Huang, Qitao Yan, Guiming Chen, Zhanguo Liu
Format: Article
Language:English
Published: PeerJ Inc. 2017-03-01
Series:PeerJ
Subjects:
Online Access:https://peerj.com/articles/3108.pdf
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author Ping Chang
Bing Mo
David M. Cauvi
Ying Yu
Zhenhui Guo
Jian Zhou
Qiong Huang
Qitao Yan
Guiming Chen
Zhanguo Liu
author_facet Ping Chang
Bing Mo
David M. Cauvi
Ying Yu
Zhenhui Guo
Jian Zhou
Qiong Huang
Qitao Yan
Guiming Chen
Zhanguo Liu
author_sort Ping Chang
collection DOAJ
description Apoptosis of lymphocytes is associated with immunosuppression and poor prognosis in sepsis. Our previous report showed that histones, nuclear proteins released from damaged or dying cells in sepsis, can mediate lymphocyte apoptosis via mitochondria damage. Grape seed proanthocyanidin extract (GSPE), a natural substance with protective properties against oxidative stress, plays a vital role in cell and mitochondria protection. We thus hypothesized that GSPE may play a protective role in histone-induced lymphocyte apoptosis through its anti-oxidative properties. In this study, we investigated the protective efficacy of GSPE on lymphocyte apoptosis induced by extracellular histones, a main contributor of death in sepsis. Human blood lymphocytes were treated with 50 μg/ml histones, 2 μg/ml GSPE, or a combination of both. A total of 100 μM N-acetylcysteine (NAC), a reactive oxygen species (ROS) inhibitor, was used as a positive control for GSPE. Apoptosis, intracellular ROS levels, mitochondrial membrane potential, Bcl-2 expression, and caspase-3 cleavage were measured. Our data clearly indicate that GSPE significantly inhibited lymphocyte apoptosis, generation of ROS, the loss of mitochondrial membrane potential, the decrease in Bcl-2 expression, and caspase-3 activation induced by extracellular histones. In conclusion, we show that GSPE has a protective effect on lymphocyte apoptosis induced by extracellular histones. This study suggests GSPE as a potential therapeutic agent that could help reduce lymphocyte apoptosis, and thus the state of immunosuppression was observed in septic patients.
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spelling doaj.art-e00195c2fc784a52881ffe70a68375282023-12-03T10:55:06ZengPeerJ Inc.PeerJ2167-83592017-03-015e310810.7717/peerj.3108Grape seed proanthocyanidin extract protects lymphocytes against histone-induced apoptosisPing Chang0Bing Mo1David M. Cauvi2Ying Yu3Zhenhui Guo4Jian Zhou5Qiong Huang6Qitao Yan7Guiming Chen8Zhanguo Liu9Department of ICU, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of ICU, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of Surgery, University of California San Diego, La Jolla, CA, USADepartment of ICU, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of MICU, General Hospital of Guangzhou Military Command, Guangzhou, Guangdong, ChinaDepartment of ICU, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of ICU, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of MICU, General Hospital of Guangzhou Military Command, Guangzhou, Guangdong, ChinaDepartment of ICU, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, ChinaDepartment of ICU, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, ChinaApoptosis of lymphocytes is associated with immunosuppression and poor prognosis in sepsis. Our previous report showed that histones, nuclear proteins released from damaged or dying cells in sepsis, can mediate lymphocyte apoptosis via mitochondria damage. Grape seed proanthocyanidin extract (GSPE), a natural substance with protective properties against oxidative stress, plays a vital role in cell and mitochondria protection. We thus hypothesized that GSPE may play a protective role in histone-induced lymphocyte apoptosis through its anti-oxidative properties. In this study, we investigated the protective efficacy of GSPE on lymphocyte apoptosis induced by extracellular histones, a main contributor of death in sepsis. Human blood lymphocytes were treated with 50 μg/ml histones, 2 μg/ml GSPE, or a combination of both. A total of 100 μM N-acetylcysteine (NAC), a reactive oxygen species (ROS) inhibitor, was used as a positive control for GSPE. Apoptosis, intracellular ROS levels, mitochondrial membrane potential, Bcl-2 expression, and caspase-3 cleavage were measured. Our data clearly indicate that GSPE significantly inhibited lymphocyte apoptosis, generation of ROS, the loss of mitochondrial membrane potential, the decrease in Bcl-2 expression, and caspase-3 activation induced by extracellular histones. In conclusion, we show that GSPE has a protective effect on lymphocyte apoptosis induced by extracellular histones. This study suggests GSPE as a potential therapeutic agent that could help reduce lymphocyte apoptosis, and thus the state of immunosuppression was observed in septic patients.https://peerj.com/articles/3108.pdfGrape seed proanthocyanidin extractLymphocyte apoptosisMitochondrial injuryHistonesReactive oxygen species
spellingShingle Ping Chang
Bing Mo
David M. Cauvi
Ying Yu
Zhenhui Guo
Jian Zhou
Qiong Huang
Qitao Yan
Guiming Chen
Zhanguo Liu
Grape seed proanthocyanidin extract protects lymphocytes against histone-induced apoptosis
PeerJ
Grape seed proanthocyanidin extract
Lymphocyte apoptosis
Mitochondrial injury
Histones
Reactive oxygen species
title Grape seed proanthocyanidin extract protects lymphocytes against histone-induced apoptosis
title_full Grape seed proanthocyanidin extract protects lymphocytes against histone-induced apoptosis
title_fullStr Grape seed proanthocyanidin extract protects lymphocytes against histone-induced apoptosis
title_full_unstemmed Grape seed proanthocyanidin extract protects lymphocytes against histone-induced apoptosis
title_short Grape seed proanthocyanidin extract protects lymphocytes against histone-induced apoptosis
title_sort grape seed proanthocyanidin extract protects lymphocytes against histone induced apoptosis
topic Grape seed proanthocyanidin extract
Lymphocyte apoptosis
Mitochondrial injury
Histones
Reactive oxygen species
url https://peerj.com/articles/3108.pdf
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