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Thromb Haemost 2021; 121(07): 931-943
DOI: 10.1055/s-0040-1722621
Cellular Haemostasis and Platelets

Protocatechuic Acid Protects Platelets from Apoptosis via Inhibiting Oxidative Stress-Mediated PI3K/Akt/GSK3β Signaling

Fuli Ya‡   *
1   Department of Nutrition and Food Safety, School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong Province, China
2   Guangdong Provincial Key Laboratory for Food, Nutrition and Health, Guangzhou, Guangdong Province, China
3   Guangdong Engineering Technology Research Center of Nutrition Translation, Guangzhou, Guangdong Province, China
,
Kongyao Li‡   *
1   Department of Nutrition and Food Safety, School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong Province, China
2   Guangdong Provincial Key Laboratory for Food, Nutrition and Health, Guangzhou, Guangdong Province, China
3   Guangdong Engineering Technology Research Center of Nutrition Translation, Guangzhou, Guangdong Province, China
,
Hong Chen
1   Department of Nutrition and Food Safety, School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong Province, China
2   Guangdong Provincial Key Laboratory for Food, Nutrition and Health, Guangzhou, Guangdong Province, China
3   Guangdong Engineering Technology Research Center of Nutrition Translation, Guangzhou, Guangdong Province, China
,
Zezhong Tian
1   Department of Nutrition and Food Safety, School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong Province, China
2   Guangdong Provincial Key Laboratory for Food, Nutrition and Health, Guangzhou, Guangdong Province, China
3   Guangdong Engineering Technology Research Center of Nutrition Translation, Guangzhou, Guangdong Province, China
,
Die Fan
1   Department of Nutrition and Food Safety, School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong Province, China
2   Guangdong Provincial Key Laboratory for Food, Nutrition and Health, Guangzhou, Guangdong Province, China
3   Guangdong Engineering Technology Research Center of Nutrition Translation, Guangzhou, Guangdong Province, China
,
Yilin Shi
2   Guangdong Provincial Key Laboratory for Food, Nutrition and Health, Guangzhou, Guangdong Province, China
3   Guangdong Engineering Technology Research Center of Nutrition Translation, Guangzhou, Guangdong Province, China
4   Department of Nutrition, School of Public Health (Northern Campus), Sun Yat-sen University, Guangzhou, Guangdong Province, China
,
Fenglin Song
5   Department of Food Safety, School of Food Science, Guangdong Pharmaceutical University, Guangzhou, Guangdong Province, China
,
Xiping Xu
6   Renal Division, National Clinical Research Center for Kidney Disease, Southern Medical University, Nanfang Hospital, Guangzhou, Guangdong Province, China
,
Wenhua Ling
2   Guangdong Provincial Key Laboratory for Food, Nutrition and Health, Guangzhou, Guangdong Province, China
3   Guangdong Engineering Technology Research Center of Nutrition Translation, Guangzhou, Guangdong Province, China
4   Department of Nutrition, School of Public Health (Northern Campus), Sun Yat-sen University, Guangzhou, Guangdong Province, China
,
Reheman Adili
7   Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, United States
,
Yan Yang
1   Department of Nutrition and Food Safety, School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong Province, China
2   Guangdong Provincial Key Laboratory for Food, Nutrition and Health, Guangzhou, Guangdong Province, China
3   Guangdong Engineering Technology Research Center of Nutrition Translation, Guangzhou, Guangdong Province, China
› Author Affiliations Funding This work was supported by the Guangzhou Science, Technology, and Innovation Commission (No. 201804020045), the Key Project of National Natural Science Foundation of China (No. 81730090 and No. 82030098), the National Natural Science Foundation of China (No. 81872617), and the Shenzhen Science and Technology Innovation Commission (No. 201803073000433).
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Abstract

Oxidative stress plays crucial roles in initiating platelet apoptosis that facilitates the progression of cardiovascular diseases (CVDs). Protocatechuic acid (PCA), a major metabolite of anthocyanin cyanidin-3-O-β-glucoside (Cy-3-g), exerts cardioprotective effects. However, underlying mechanisms responsible for such effects remain unclear. Here, we investigate the effect of PCA on platelet apoptosis and the underlying mechanisms in vitro. Isolated human platelets were treated with hydrogen peroxide (H2O2) to induce apoptosis with or without pretreatment with PCA. We found that PCA dose-dependently inhibited H2O2-induced platelet apoptosis by decreasing the dissipation of mitochondrial membrane potential, activation of caspase-9 and caspase-3, and decreasing phosphatidylserine exposure. Additionally, the distributions of Bax, Bcl-xL, and cytochrome c mediated by H2O2 in the mitochondria and the cytosol were also modulated by PCA treatment. Moreover, the inhibitory effects of PCA on platelet caspase-3 cleavage and phosphatidylserine exposure were mainly mediated by downregulating PI3K/Akt/GSK3β signaling. Furthermore, PCA dose-dependently decreased reactive oxygen species (ROS) generation and the intracellular Ca2+ concentration in platelets in response to H2O2. N-Acetyl cysteine (NAC), a ROS scavenger, markedly abolished H2O2-stimulated PI3K/Akt/GSK3β signaling, caspase-3 activation, and phosphatidylserine exposure. The combination of NAC and PCA did not show significant additive inhibitory effects on PI3K/Akt/GSK3β signaling and platelet apoptosis. Thus, our results suggest that PCA protects platelets from oxidative stress-induced apoptosis through downregulating ROS-mediated PI3K/Akt/GSK3β signaling, which may be responsible for cardioprotective roles of PCA in CVDs.

Keywords

anthocyanin - protocatechuic acid - platelet apoptosis - reactive oxygen species - oxidative stress

* These authors contributed equally to this work.


Supplementary Material



Publication History

Received: 21 December 2019

Accepted: 30 November 2020

Article published online:
05 February 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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