Activation of AMPK participates hydrogen sulfide-induced cyto-protective effect against dexamethasone in osteoblastic MC3T3-E1 cells |
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Authors: | Ming Yang Yue HuangJia Chen Yi-lei ChenJian-jun Ma Pei-hua Shi |
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Affiliation: | Department of Orthopaedics, Sir Run Run Shaw Hospital of Medical College of Zhejiang University, Hangzhou, Zhejiang 310016, China |
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Abstract: | 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. |
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Keywords: | AMPK, adenosine monophosphate (AMP)-activated protein kinase ACC, acetyl-CoA carboxylase CBS, cystathionine β-synthase CSE, cystathionine γ-lyase Dex, dexamethasone GCs, glucocorticoids H2S, hydrogen sulfide LDH, lactate dehydrogenase MTT, methyl thiazolyl tetrazolium ROS, reactive oxygen species SAM, S-adenosyl-l-methionine |
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