Protective Effect of Phloroglucinol on Oxidative Stress-Induced DNA Damage and Apoptosis through Activation of the Nrf2/HO-1 Signaling Pathway in HaCaT Human Keratinocytes
Phloroglucinol (PG) is a component of phlorotannins, which are abundant in marine brown alga species. Recent studies have shown that PG is beneficial in protecting cells from oxidative stress. In this study, we evaluated the protective efficacy of PG in HaCaT human skin keratinocytes stimulated with...
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MDPI AG
2019-04-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/17/4/225 |
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| author | Cheol Park Hee-Jae Cha Su Hyun Hong Gi-Young Kim Suhkmann Kim Heui-Soo Kim Byung Woo Kim You-Jin Jeon Yung Hyun Choi |
| author_facet | Cheol Park Hee-Jae Cha Su Hyun Hong Gi-Young Kim Suhkmann Kim Heui-Soo Kim Byung Woo Kim You-Jin Jeon Yung Hyun Choi |
| author_sort | Cheol Park |
| collection | DOAJ |
| description | Phloroglucinol (PG) is a component of phlorotannins, which are abundant in marine brown alga species. Recent studies have shown that PG is beneficial in protecting cells from oxidative stress. In this study, we evaluated the protective efficacy of PG in HaCaT human skin keratinocytes stimulated with oxidative stress (hydrogen peroxide, H<sub>2</sub>O<sub>2</sub>). The results showed that PG significantly inhibited the H<sub>2</sub>O<sub>2</sub>-induced growth inhibition in HaCaT cells, which was associated with increased expression of heme oxygenase-1 (HO-1) by the activation of nuclear factor erythroid 2-related factor-2 (Nrf2). PG remarkably reversed H<sub>2</sub>O<sub>2</sub>-induced excessive ROS production, DNA damage, and apoptosis. Additionally, H<sub>2</sub>O<sub>2</sub>-induced mitochondrial dysfunction was related to a decrease in ATP levels, and in the presence of PG, these changes were significantly impaired. Furthermore, the increases of cytosolic release of cytochrome <i>c</i> and ratio of Bax to Bcl-2, and the activation of caspase-9 and caspase-3 by the H<sub>2</sub>O<sub>2</sub> were markedly abolished under the condition of PG pretreatment. However, the inhibition of HO-1 function using zinc protoporphyrin, a HO-1 inhibitor, markedly attenuated these protective effects of PG against H<sub>2</sub>O<sub>2</sub>. Overall, our results suggest that PG is able to protect HaCaT keratinocytes against oxidative stress-induced DNA damage and apoptosis through activating the Nrf2/HO-1 signaling pathway. |
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| last_indexed | 2024-04-13T07:22:12Z |
| publishDate | 2019-04-01 |
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| series | Marine Drugs |
| spelling | doaj.art-3094720b4f6444ddb40443fc742c616f2022-12-22T02:56:35ZengMDPI AGMarine Drugs1660-33972019-04-0117422510.3390/md17040225md17040225Protective Effect of Phloroglucinol on Oxidative Stress-Induced DNA Damage and Apoptosis through Activation of the Nrf2/HO-1 Signaling Pathway in HaCaT Human KeratinocytesCheol Park0Hee-Jae Cha1Su Hyun Hong2Gi-Young Kim3Suhkmann Kim4Heui-Soo Kim5Byung Woo Kim6You-Jin Jeon7Yung Hyun Choi8Department of Molecular Biology, College of Natural Sciences, Dong-eui University, Busan 47340, KoreaDepartment of Parasitology and Genetics, College of Medicine, Kosin University, Busan 49267, KoreaDepartment of Biochemistry, Dong-eui University College of Korean Medicine, Busan 47227, KoreaDepartment of Marine Life Sciences, School of Marine Biomedical Sciences, Jeju National University, Jeju 63243, KoreaDepartment of Chemistry, College of Natural Sciences, Pusan National University, Busan 46241, KoreaDepartment of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 46241, KoreaBiopharmaceutical Engineering Major, Division of Applied Bioengineering, College of Engineering, Dong-eui University, Busan 47340, KoreaDepartment of Marine Life Sciences, School of Marine Biomedical Sciences, Jeju National University, Jeju 63243, KoreaDepartment of Biochemistry, Dong-eui University College of Korean Medicine, Busan 47227, KoreaPhloroglucinol (PG) is a component of phlorotannins, which are abundant in marine brown alga species. Recent studies have shown that PG is beneficial in protecting cells from oxidative stress. In this study, we evaluated the protective efficacy of PG in HaCaT human skin keratinocytes stimulated with oxidative stress (hydrogen peroxide, H<sub>2</sub>O<sub>2</sub>). The results showed that PG significantly inhibited the H<sub>2</sub>O<sub>2</sub>-induced growth inhibition in HaCaT cells, which was associated with increased expression of heme oxygenase-1 (HO-1) by the activation of nuclear factor erythroid 2-related factor-2 (Nrf2). PG remarkably reversed H<sub>2</sub>O<sub>2</sub>-induced excessive ROS production, DNA damage, and apoptosis. Additionally, H<sub>2</sub>O<sub>2</sub>-induced mitochondrial dysfunction was related to a decrease in ATP levels, and in the presence of PG, these changes were significantly impaired. Furthermore, the increases of cytosolic release of cytochrome <i>c</i> and ratio of Bax to Bcl-2, and the activation of caspase-9 and caspase-3 by the H<sub>2</sub>O<sub>2</sub> were markedly abolished under the condition of PG pretreatment. However, the inhibition of HO-1 function using zinc protoporphyrin, a HO-1 inhibitor, markedly attenuated these protective effects of PG against H<sub>2</sub>O<sub>2</sub>. Overall, our results suggest that PG is able to protect HaCaT keratinocytes against oxidative stress-induced DNA damage and apoptosis through activating the Nrf2/HO-1 signaling pathway.https://www.mdpi.com/1660-3397/17/4/225phloroglucinolkeratinocytesoxidative stressROSNrf2/HO-1 |
| spellingShingle | Cheol Park Hee-Jae Cha Su Hyun Hong Gi-Young Kim Suhkmann Kim Heui-Soo Kim Byung Woo Kim You-Jin Jeon Yung Hyun Choi Protective Effect of Phloroglucinol on Oxidative Stress-Induced DNA Damage and Apoptosis through Activation of the Nrf2/HO-1 Signaling Pathway in HaCaT Human Keratinocytes Marine Drugs phloroglucinol keratinocytes oxidative stress ROS Nrf2/HO-1 |
| title | Protective Effect of Phloroglucinol on Oxidative Stress-Induced DNA Damage and Apoptosis through Activation of the Nrf2/HO-1 Signaling Pathway in HaCaT Human Keratinocytes |
| title_full | Protective Effect of Phloroglucinol on Oxidative Stress-Induced DNA Damage and Apoptosis through Activation of the Nrf2/HO-1 Signaling Pathway in HaCaT Human Keratinocytes |
| title_fullStr | Protective Effect of Phloroglucinol on Oxidative Stress-Induced DNA Damage and Apoptosis through Activation of the Nrf2/HO-1 Signaling Pathway in HaCaT Human Keratinocytes |
| title_full_unstemmed | Protective Effect of Phloroglucinol on Oxidative Stress-Induced DNA Damage and Apoptosis through Activation of the Nrf2/HO-1 Signaling Pathway in HaCaT Human Keratinocytes |
| title_short | Protective Effect of Phloroglucinol on Oxidative Stress-Induced DNA Damage and Apoptosis through Activation of the Nrf2/HO-1 Signaling Pathway in HaCaT Human Keratinocytes |
| title_sort | protective effect of phloroglucinol on oxidative stress induced dna damage and apoptosis through activation of the nrf2 ho 1 signaling pathway in hacat human keratinocytes |
| topic | phloroglucinol keratinocytes oxidative stress ROS Nrf2/HO-1 |
| url | https://www.mdpi.com/1660-3397/17/4/225 |
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