Cellular Physiology and Biochemistry (May 2013)

Hydrogen Sulfide Inhibits Abnormal Proliferation of Lymphocytes via AKT/GSK3β Signal Pathway in Systemic Lupus Erythematosus Patients

  • Yanfang Han,
  • Fanqin Zeng,
  • Guozhen Tan,
  • Chuntao Yang,
  • Hongfeng Tang,
  • Yijin Luo,
  • Jianqiang Feng,
  • Hui Xiong,
  • Qing Guo

DOI
https://doi.org/10.1159/000350097
Journal volume & issue
Vol. 31, no. 6
pp. 795 – 804

Abstract

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Background/Aim: The abnormal activation of the AKT/GSK3β signal pathway in lymphocytes from systemic lupus erythematosus (SLE) patients plays an important role in the pathogenesis of the disease. Recently Hydrogen sulfide (H2S) has been recognized as a crucial gaseous signaling molecule, involved in regulation of cell proliferation. However, the role of H2S in regulating the abnormal activation of lymphocytes from SLE patients has not been established. This study was conducted to investigate the effect of H2S on lymphocytes and to explore the mechanisms involved. Methods: The lymphocytes were isolated from SLE patients with or without renal disease and healthy controls. The cells were treated as indicated in each experiment. Cell viability was analyzed by CCK-8. Cell cycle distribution was determined by flow cytometry. Western blot was used to detect the expression of phosphorylated AKT (ser473), GSK3β (ser9) and CDK2, p27Kip1 and p21WAF1/CIP1. Results: Our findings showed that proliferation of lymphocytes was stimulated following treatment with NaHS (a H2S donor) at low NaHS concentrations (2mM). Similar results were observed using GYY4137, which is a slow-releasing H2S donor. Pretreatment of lymphocytes from SLE patients with NaHS at high concentrations prior to exposure to phytohemagglutinin (PHA) significantly attenuated proliferation, evidenced by decrease in cell viability and S phase distribution of cell cycle. Pretreatment with NaHS decreased PHA-induced expression of CDK2, phosphorylation levels of AKT (ser473) and GSK3β (ser9) and increased the expression of p27Kip1 and p21WAF1/CIP1. Moreover, pretreatment with NaHS blunted the stimulation of SLE lymphocyte proliferation by GSK3β inhibitor lithium chloride. Conclusion: These results demonstrate that H2S inhibits the abnormal activation of lymphocytes from SLE patients throuqh the AKT/GSK3β signal pathway.

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