The Protective Role of Autophagy in Heterocephalus glaber Hepatic Stellate Cells Exposed to H2O2 or Nutritional Stress

Abstract

Background/Aims: Naked mole rats (NMRs) survive and thrive in dark, dank environments with low levels of oxygen and poor quality nutrition. Their long lifespan is attributed to sustained good health and pronounced resistance to cancer. Physiological and biochemical processes, such as autophagy, may contribute to the successful aging of this exceptionally long-lived species. We demonstrated that NMRs have higher levels of autophagy than short-lived C57BL/6 mice, and this may play an important role in the maintenance of cellular protein quality and the defense of cells against intracellular and extracellular aggressors in NMRs. The present study assesses autophagy as a means for cells to flexibly respond to environmental changes (H₂O₂ treatment and a shortage of nutrients). Methods: Primary NMR HSCs were isolated from liver and treated with serum-free medium. Cells in the experimental group were incubated with different concentrations of hydrogen peroxide (H₂O₂) in the presence and / or absence of 3-MA (5 mM).The LC3-II/LC3-I ratio was determined by western blot analysis. Western blotting was performed to analyze the expression level of Beclin 1 protein. Apoptosis and cell-cycle progression were analyzed by flow cytometry. Results: Our data reveal that both poor quality nutrition and H₂O₂ treatment induces apoptosis and autophagy in NMR hepatic stellate cells(HSCs). Conclusion: NMR cells have the capacity to induce cell death through apoptosis and downregulate the energy consuming processes through inhibition of proliferation when they become superfluous or irreversibly damaged.