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Naked mole-rat very-high-molecular-mass hyaluronan exhibits superior cytoprotective properties

Author

Listed:
  • Masaki Takasugi

    (University of Rochester)

  • Denis Firsanov

    (University of Rochester)

  • Gregory Tombline

    (University of Rochester)

  • Hanbing Ning

    (The First Affiliated Hospital of Zhengzhou University, Zhengzhou)

  • Julia Ablaeva

    (University of Rochester)

  • Andrei Seluanov

    (University of Rochester)

  • Vera Gorbunova

    (University of Rochester)

Abstract

Naked mole-rat (NMR), the longest-living rodent, produces very-high-molecular-mass hyaluronan (vHMM-HA), compared to other mammalian species. However, it is unclear if exceptional polymer length of vHMM-HA is important for longevity. Here, we show that vHMM-HA (>6.1 MDa) has superior cytoprotective properties compared to the shorter HMM-HA. It protects not only NMR cells, but also mouse and human cells from stress-induced cell-cycle arrest and cell death in a polymer length-dependent manner. The cytoprotective effect is dependent on the major HA-receptor, CD44. We find that vHMM-HA suppresses CD44 protein-protein interactions, whereas HMM-HA promotes them. As a result, vHMM-HA and HMM-HA induce opposing effects on the expression of CD44-dependent genes, which are associated with the p53 pathway. Concomitantly, vHMM-HA partially attenuates p53 and protects cells from stress in a p53-dependent manner. Our results implicate vHMM-HA in anti-aging mechanisms and suggest the potential applications of vHMM-HA for enhancing cellular stress resistance.

Suggested Citation

  • Masaki Takasugi & Denis Firsanov & Gregory Tombline & Hanbing Ning & Julia Ablaeva & Andrei Seluanov & Vera Gorbunova, 2020. "Naked mole-rat very-high-molecular-mass hyaluronan exhibits superior cytoprotective properties," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16050-w
    DOI: 10.1038/s41467-020-16050-w
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    Cited by:

    1. Yang Zhao & Zhizhong Zheng & Zhihui Zhang & Yandong Xu & Eric Hillpot & Yifei S. Lin & Frances T. Zakusilo & J. Yuyang Lu & Julia Ablaeva & Seyed Ali Biashad & Richard A. Miller & Eviatar Nevo & Andre, 2023. "Evolution of high-molecular-mass hyaluronic acid is associated with subterranean lifestyle," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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