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Investigating the Cytoprotective Mechanisms of the Tardigrade Damage Suppressor (Dsup) Protein in Human Cells Under

Enxhi Shaba1, Claudia Ricci2, Lorenza Vantaggiato1

  • 1Functional Proteomics Lab, Department of Life Sciences, University of Siena, 53100 Siena, Italy.

International Journal of Molecular Sciences
|November 13, 2025
PubMed

Insights

The tardigrade damage suppressor protein (Dsup) protects human cells from ischemia/reperfusion injury (IRI) by reducing oxidative stress. Dsup enhances cell survival and upregulates antioxidant proteins, showing therapeutic potential for IRI.

Area of Science:

  • Biochemistry and Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Ischemia/reperfusion injury (IRI) causes significant cell damage, primarily through reactive oxygen species (ROS) production.
  • Tardigrade damage suppressor protein (Dsup) confers resistance to oxidative stress in tardigrades.
  • Investigating Dsup's protective role in human cells against IRI is crucial.

Purpose of the Study:

  • To evaluate the protective effects of tardigrade Dsup against IRI in human cells.
  • To elucidate the molecular mechanisms underlying Dsup-mediated protection.
  • To assess Dsup's potential as a therapeutic agent for IRI.

Main Methods:

  • Established an in vitro model of hypoxia and reoxygenation using HEK293TT cells.
  • Expressed Dsup in human cells and analyzed cell viability and intracellular ROS levels.
  • Utilized proteomic and Western blot analyses to assess antioxidant protein expression and pathway modulation.

Main Results:

  • Dsup expression significantly improved cell survival following hypoxia-reoxygenation.
  • Dsup markedly reduced intracellular ROS levels in stressed human cells.
  • Proteomic analysis revealed Dsup upregulates antioxidant enzymes and modulates autophagy and MAPK signaling pathways.

Conclusions:

  • Tardigrade Dsup effectively protects human cells from IRI by mitigating oxidative stress.
  • Dsup enhances cellular defense mechanisms through antioxidant enzyme upregulation and modulation of stress-related pathways.
  • Dsup represents a promising therapeutic candidate for IRI, warranting further in vivo investigation.
Keywords:
Dsupautophagyischemiaoxidative stressproteomicsreperfusion

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