Activation of AMPK participates hydrogen sulfide-induced cyto-protective effect against dexamethasone in osteoblastic MC3T3-E1 cells

• Published in: Biochemical and biophysical research communications Vol. 454; no. 1; pp. 42 - 47
• Main Authors: Yang, Ming, Huang, Yue, Chen, Jia, Chen, Yi-lei, Ma, Jian-jun, Shi, Pei-hua
• Format: Journal Article
• Language: English
• Published: United States 07.11.2014
• Subjects: 3T3 Cells; Adenosine Triphosphate - metabolism; AMP-Activated Protein Kinases - antagonists & inhibitors; AMP-Activated Protein Kinases - genetics; AMP-Activated Protein Kinases - metabolism; Animals; Apoptosis - drug effects; Cell Survival - drug effects; Cystathionine beta-Synthase - metabolism; Cystathionine gamma-Lyase - metabolism; Cytoprotection - drug effects; Dexamethasone - antagonists & inhibitors; Dexamethasone - toxicity; Enzyme Activation; Gene Knockdown Techniques; Humans; Hydrogen Sulfide - pharmacology; Mice; Osteoblasts - drug effects; Osteoblasts - metabolism; Osteoblasts - pathology; Osteonecrosis - metabolism; Osteonecrosis - pathology; Osteonecrosis - prevention & control; Reactive Oxygen Species - metabolism; RNA, Small Interfering - genetics; AMPK and oxidative stress; Hydrogen sulfide; Osteoporosis; Dexamethasone
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2014.10.033

Long-time glucocorticoids (GCs) usage causes osteoporosis. In the present study, we explored the potential role of hydrogen sulfide (H2S) against dexamethasone (Dex)-induced osteoblast cell damage, and focused on the underlying mechanisms. We showed that two H2S-producing enzymes, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), were significantly downregulated in human osteonecrosis tissues as well as in Dex-treated osteoblastic MC3T3-E1 cells. H2S donor NaHS as well as the CBS activator S-adenosyl-l-methionine (SAM) inhibited Dex-induced viability reduction, death and apoptosis in MC3T3-E1 cells. NaHS activated adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling, which participated its cyto-protective activity. AMPK inhibition by its inhibitor (compound C) or reduction by targeted-shRNA suppressed its pro-survival activity against Dex in MC3T3-E1 cells. Further, we found that NaHS inhibited Dex-mediated reactive oxygen species (ROS) production and ATP depletion. Such effects by NaHS were again inhibited by compound C and AMPKα1-shRNA. In summary, we show that H2S inhibits Dex-induced osteoblast damage through activation of AMPK signaling. H2S signaling might be further investigated as a novel target for anti-osteoporosis treatment.