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

Cellular Physiology and Biochemistry

关键词: AKT;    GSK3β;    Cell cycle;    Hydrogen sulfide;    Lymphocytes;    Systemic lupus erythematosus;   

DOI  :  10.1159/000350097

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

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, p27^Kip1 and p21^WAF1/CIP1. Results Our findings showed that proliferation of lymphocytes was stimulated following treatment with NaHS (a H₂S donor) at low NaHS concentrations (<1mM) but inhibited at high 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 p27^Kip1 and p21^WAF1/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.

【 授权许可】

CC BY-NC-ND