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Nectandrin B-mediated activation of the AMPK pathway prevents cellular senescence in human diploid fibroblasts by reducing intracellular ROS levels.

Abstract

Nectandrin B (NecB) is a bioactive lignan compound isolated from Myristica fragrans (nutmeg), which functions as an activator of AMP-activated protein kinase (AMPK). Because we recently found that treatment with NecB increased the cell viability of old human diploid fibroblasts (HDFs), the underlying molecular mechanism was investigated. NecB treatment in old HDFs reduced the activity staining of senescence-associated β-galactosidase and the levels of senescence markers, such as the Ser15 phosphorylated p53, caveolin-1, p21waf1, p16ink4a, p27kip1, and cyclin D1. NecB treatment increased that in S phase, indicating a enhancement of cell cycle entry. Interestingly, NecB treatment ameliorated age-dependent activation of AMPK in old HDFs. Moreover, NecB reversed the age-dependent expression and/or activity changes of certain sirtuins (SIRT1-5), and cell survival/death-related proteins. The transcriptional activity of Yin-Yang 1 and the expression of downstream proteins were elevated in NecB-treated old HDFs. In addition, NecB treatment exerted a radical scavenging effect in vitro, reduced cellular ROS levels, and increased antioxidant enzymes in old HDFs. Moreover, NecB-mediated activation of the AMPK pathway reduced intracellular ROS levels. These results suggest that NecB-induced protection against cellular senescence is mediated by ROS-scavenging through activation of AMPK. NecB might be useful in ameliorating age-related diseases and extending human lifespan.

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  • Authors+Show Affiliations

    ,

    Drug & Disease Target Group, Division of Bioconvergence Analysis, Korea Basic Science Institute, Daejeon 305-333, Republic of Korea. Department of Biological Sciences, Sungkyunkwan University, Suwon 16419, Republic of Korea.

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    Drug & Disease Target Group, Division of Bioconvergence Analysis, Korea Basic Science Institute, Daejeon 305-333, Republic of Korea.

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    Korea Bioactive Natural Material Bank, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.

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    Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon 21999, Republic of Korea.

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    Neuroscience Research Institute, Korea University College of Medicine, Seoul 136-705, Republic of Korea.

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    East-West Cancer Center, Daejeon University, Daejeon, 302-120, Republic of Korea.

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    East-West Cancer Center, Daejeon University, Daejeon, 302-120, Republic of Korea.

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    Drug & Disease Target Group, Division of Bioconvergence Analysis, Korea Basic Science Institute, Daejeon 305-333, Republic of Korea.

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    Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon 21999, Republic of Korea. Department of Biochemistry, College of Medicine, Gachon University, Incheon 21999, Republic of Korea.

    Drug & Disease Target Group, Division of Bioconvergence Analysis, Korea Basic Science Institute, Daejeon 305-333, Republic of Korea. Division of Analytical Science, University of Science and Technology, Daejeon 34113, Republic of Korea.

    Source

    Aging 11:11 2019 Jun 14 pg 3731-3749

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31199782

    Citation

    Jang, Hyun-Jin, et al. "Nectandrin B-mediated Activation of the AMPK Pathway Prevents Cellular Senescence in Human Diploid Fibroblasts By Reducing Intracellular ROS Levels." Aging, vol. 11, no. 11, 2019, pp. 3731-3749.
    Jang HJ, Yang KE, Oh WK, et al. Nectandrin B-mediated activation of the AMPK pathway prevents cellular senescence in human diploid fibroblasts by reducing intracellular ROS levels. Aging (Albany NY). 2019;11(11):3731-3749.
    Jang, H. J., Yang, K. E., Oh, W. K., Lee, S. I., Hwang, I. H., Ban, K. T., ... Jang, I. S. (2019). Nectandrin B-mediated activation of the AMPK pathway prevents cellular senescence in human diploid fibroblasts by reducing intracellular ROS levels. Aging, 11(11), pp. 3731-3749. doi:10.18632/aging.102013.
    Jang HJ, et al. Nectandrin B-mediated Activation of the AMPK Pathway Prevents Cellular Senescence in Human Diploid Fibroblasts By Reducing Intracellular ROS Levels. Aging (Albany NY). 2019 Jun 14;11(11):3731-3749. PubMed PMID: 31199782.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Nectandrin B-mediated activation of the AMPK pathway prevents cellular senescence in human diploid fibroblasts by reducing intracellular ROS levels. AU - Jang,Hyun-Jin, AU - Yang,Kyeong Eun, AU - Oh,Won Keun, AU - Lee,Song-I, AU - Hwang,In-Hu, AU - Ban,Kyung-Tae, AU - Yoo,Hwa-Seung, AU - Choi,Jong-Soon, AU - Yeo,Eui-Ju, AU - Jang,Ik-Soon, PY - 2019/03/12/received PY - 2019/05/31/accepted PY - 2019/6/15/pubmed PY - 2019/6/15/medline PY - 2019/6/15/entrez KW - AMP-activated protein kinase KW - Nectandrin B KW - cellular senescence KW - human diploid fibroblasts KW - reactive oxygen species SP - 3731 EP - 3749 JF - Aging JO - Aging (Albany NY) VL - 11 IS - 11 N2 - Nectandrin B (NecB) is a bioactive lignan compound isolated from Myristica fragrans (nutmeg), which functions as an activator of AMP-activated protein kinase (AMPK). Because we recently found that treatment with NecB increased the cell viability of old human diploid fibroblasts (HDFs), the underlying molecular mechanism was investigated. NecB treatment in old HDFs reduced the activity staining of senescence-associated β-galactosidase and the levels of senescence markers, such as the Ser15 phosphorylated p53, caveolin-1, p21waf1, p16ink4a, p27kip1, and cyclin D1. NecB treatment increased that in S phase, indicating a enhancement of cell cycle entry. Interestingly, NecB treatment ameliorated age-dependent activation of AMPK in old HDFs. Moreover, NecB reversed the age-dependent expression and/or activity changes of certain sirtuins (SIRT1-5), and cell survival/death-related proteins. The transcriptional activity of Yin-Yang 1 and the expression of downstream proteins were elevated in NecB-treated old HDFs. In addition, NecB treatment exerted a radical scavenging effect in vitro, reduced cellular ROS levels, and increased antioxidant enzymes in old HDFs. Moreover, NecB-mediated activation of the AMPK pathway reduced intracellular ROS levels. These results suggest that NecB-induced protection against cellular senescence is mediated by ROS-scavenging through activation of AMPK. NecB might be useful in ameliorating age-related diseases and extending human lifespan. SN - 1945-4589 UR - https://www.unboundmedicine.com/medline/citation/31199782/Nectandrin_B-mediated_activation_of_the_AMPK_pathway_prevents_cellular_senescence_in_human_diploid_fibroblasts_by_reducing_intracellular_ROS_levels L2 - https://www.impactaging.com/full/11/3731 DB - PRIME DP - Unbound Medicine ER -