FK866 Protects Human Dental Pulp Cells against Oxidative Stress-Induced Cellular Senescence

FK866 possesses various functional properties, such as anti-angiogenic, anti-cancer, and anti-inflammatory activities. We previously demonstrated that premature senescence of human dental pulp cells (hDPCs) was induced by hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>). The pr...

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Main Authors: Chang Youp Ok, Sera Park, Hye-Ock Jang, Takashi Takata, Ok-Hee Lee, Moon-Kyoung Bae, Soo-Kyung Bae
Format: Article
Language:English
Published: MDPI AG 2021-02-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/10/2/271
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author Chang Youp Ok
Sera Park
Hye-Ock Jang
Takashi Takata
Ok-Hee Lee
Moon-Kyoung Bae
Soo-Kyung Bae
author_facet Chang Youp Ok
Sera Park
Hye-Ock Jang
Takashi Takata
Ok-Hee Lee
Moon-Kyoung Bae
Soo-Kyung Bae
author_sort Chang Youp Ok
collection DOAJ
description FK866 possesses various functional properties, such as anti-angiogenic, anti-cancer, and anti-inflammatory activities. We previously demonstrated that premature senescence of human dental pulp cells (hDPCs) was induced by hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>). The present study aimed to investigate whether H<sub>2</sub>O<sub>2</sub>-induced premature senescence of hDPCs is affected by treatment with FK866. We found that FK866 markedly inhibited the senescent characteristics of hDPCs after exposure to H<sub>2</sub>O<sub>2</sub>, as revealed by an increase in the number of senescence-associated β-galactosidase (SA-β-gal)-positive hDPCs and the upregulation of the p21 and p53 proteins, which acts as molecular indicators of cellular senescence. Moreover, the stimulatory effects of H<sub>2</sub>O<sub>2</sub> on cellular senescence are associated with oxidative stress induction, such as excessive ROS production and NADPH consumption, telomere DNA damage induction, and upregulation of senescence-associated secretory phenotype factors (IL-1β, IL-6, IL-8, COX-2, and TNF-α) as well as NF-κB activation, which were all blocked by FK866. Thus, FK866 might antagonize H<sub>2</sub>O<sub>2</sub>-induced premature senescence of hDPCs, acting as a potential therapeutic antioxidant by attenuating oxidative stress-induced pathologies in dental pulp, including inflammation and cellular senescence.
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spelling doaj.art-398c5f5a03bd4309abd4c826a2b3e0222023-12-03T13:09:41ZengMDPI AGAntioxidants2076-39212021-02-0110227110.3390/antiox10020271FK866 Protects Human Dental Pulp Cells against Oxidative Stress-Induced Cellular SenescenceChang Youp Ok0Sera Park1Hye-Ock Jang2Takashi Takata3Ok-Hee Lee4Moon-Kyoung Bae5Soo-Kyung Bae6Department of Dental Pharmacology, School of Dentistry, Education and Research Team for Life Science on Dentistry, Pusan National University, Yangsan 50612, KoreaDepartment of Dental Pharmacology, School of Dentistry, Education and Research Team for Life Science on Dentistry, Pusan National University, Yangsan 50612, KoreaDepartment of Dental Pharmacology, School of Dentistry, Education and Research Team for Life Science on Dentistry, Pusan National University, Yangsan 50612, KoreaTokuyama University, Shunan, Yamaguchi 745-8566, JapanDepartment of Biomedical Science, CHA University, Gyeonggi-do 13488, KoreaPeriodontal Disease Signaling Network Research Center, School of Dentistry, Pusan National University, Yangsan 50612, KoreaDepartment of Dental Pharmacology, School of Dentistry, Education and Research Team for Life Science on Dentistry, Pusan National University, Yangsan 50612, KoreaFK866 possesses various functional properties, such as anti-angiogenic, anti-cancer, and anti-inflammatory activities. We previously demonstrated that premature senescence of human dental pulp cells (hDPCs) was induced by hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>). The present study aimed to investigate whether H<sub>2</sub>O<sub>2</sub>-induced premature senescence of hDPCs is affected by treatment with FK866. We found that FK866 markedly inhibited the senescent characteristics of hDPCs after exposure to H<sub>2</sub>O<sub>2</sub>, as revealed by an increase in the number of senescence-associated β-galactosidase (SA-β-gal)-positive hDPCs and the upregulation of the p21 and p53 proteins, which acts as molecular indicators of cellular senescence. Moreover, the stimulatory effects of H<sub>2</sub>O<sub>2</sub> on cellular senescence are associated with oxidative stress induction, such as excessive ROS production and NADPH consumption, telomere DNA damage induction, and upregulation of senescence-associated secretory phenotype factors (IL-1β, IL-6, IL-8, COX-2, and TNF-α) as well as NF-κB activation, which were all blocked by FK866. Thus, FK866 might antagonize H<sub>2</sub>O<sub>2</sub>-induced premature senescence of hDPCs, acting as a potential therapeutic antioxidant by attenuating oxidative stress-induced pathologies in dental pulp, including inflammation and cellular senescence.https://www.mdpi.com/2076-3921/10/2/271hydrogen peroxidesenescencehuman dental pulp cellsreactive oxygen speciestelomere damageinflammation
spellingShingle Chang Youp Ok
Sera Park
Hye-Ock Jang
Takashi Takata
Ok-Hee Lee
Moon-Kyoung Bae
Soo-Kyung Bae
FK866 Protects Human Dental Pulp Cells against Oxidative Stress-Induced Cellular Senescence
Antioxidants
hydrogen peroxide
senescence
human dental pulp cells
reactive oxygen species
telomere damage
inflammation
title FK866 Protects Human Dental Pulp Cells against Oxidative Stress-Induced Cellular Senescence
title_full FK866 Protects Human Dental Pulp Cells against Oxidative Stress-Induced Cellular Senescence
title_fullStr FK866 Protects Human Dental Pulp Cells against Oxidative Stress-Induced Cellular Senescence
title_full_unstemmed FK866 Protects Human Dental Pulp Cells against Oxidative Stress-Induced Cellular Senescence
title_short FK866 Protects Human Dental Pulp Cells against Oxidative Stress-Induced Cellular Senescence
title_sort fk866 protects human dental pulp cells against oxidative stress induced cellular senescence
topic hydrogen peroxide
senescence
human dental pulp cells
reactive oxygen species
telomere damage
inflammation
url https://www.mdpi.com/2076-3921/10/2/271
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