Please use this identifier to cite or link to this item: https://doi.org/10.3389/fphar.2017.00007
Title: The new synthetic H2S-releasing SDSS protects MC3T3-E1 osteoblasts against H2O2-induced apoptosis by suppressing oxidative stress, inhibiting MAPKs, and activating the PI3K/Akt pathway
Authors: Yan X. 
Wu H. 
Wu Z. 
Hua F. 
Liang D. 
Sun H.
Yang Y.
Huang D. 
Bian J.-S. 
Keywords: 3 (3,4 dihydroxyphenyl)lactic acid
alkaline phosphatase
caspase 3
collagen
glutathione
mitogen activated protein kinase
mitogen activated protein kinase 1
phosphatidylinositol 3 kinase
protein kinase B
reactive oxygen metabolite
sialoprotein
stress activated protein kinase
superoxide dismutase
synaptophysin
transcription factor RUNX2
adult
animal cell
animal experiment
antioxidant activity
apoptosis
Article
cell damage
cell differentiation
cell protection
cell viability
controlled study
drug structure
drug synthesis
enzyme activation
extracellular matrix
high performance liquid chromatography
in vitro study
in vivo study
molecular probe
mouse
MTT assay
nonhuman
osteoblast
oxidative stress
protein expression
proton nuclear magnetic resonance
quantitative analysis
rat
reverse transcription polymerase chain reaction
sustained drug release
Issue Date: 2017
Publisher: Frontiers Media S.A.
Citation: Yan X., Wu H., Wu Z., Hua F., Liang D., Sun H., Yang Y., Huang D., Bian J.-S. (2017). The new synthetic H2S-releasing SDSS protects MC3T3-E1 osteoblasts against H2O2-induced apoptosis by suppressing oxidative stress, inhibiting MAPKs, and activating the PI3K/Akt pathway. Frontiers in Pharmacology 8 (JAN) : 7. ScholarBank@NUS Repository. https://doi.org/10.3389/fphar.2017.00007
Abstract: Reactive oxygen species (ROS) are important in osteoporosis development. Oxidative stress induces apoptosis of osteoblasts and arrest of their differentiation. Both Danshensu (DSS) and hydrogen sulfide (H2S) produce significant antioxidant effect in various systems. In this study, we synthesized SDSS, a novel H2S-releasing compound derived from DSS, and studied its antioxidant effect in an H2O2-induced MC3T3-E1 osteoblastic cell injury model. We first characterized the H2S releasing property of SDSS in both in vivo and in vitro models. HPLC chromatogram showed that intravenous injection of SDSS in adult rats released ADT-OH, a well proved H2S sustained-release moiety, within several minutes in the rat plasma. Using an H2S selective fluorescent probe, we further confirmed that SDSS released H2S in MC3T3-E1 osteoblastic cells. Biological studies revealed that SDSS had no significant toxic effect but produced protective effects against H2O2-induced MC3T3-E1 cell apoptosis. SDSS also reversed the arrest of cell differentiation caused by H2O2 treatment. This was caused by the stimulatory effect of SDSS on bone sialoprotein, runt-related transcription factor 2, collagen expression, alkaline phosphatase activity, and bone nodule formation. Further studies revealed that SDSS reversed the reduced superoxide dismutase activity and glutathione content, and the increased ROS production in H2O2 treated cells. In addition, SDSS significantly attenuated H2O2-induced activation of p38-, ERK1/2-, and JNK-MAPKs. SDSS also stimulated phosphatidylinositol 3-kinase/Akt signaling pathway. Blockade of this pathway attenuated the cytoprotective effect of SDSS. In conclusion, SDSS protects MC3T3-E1 cells against H2O2-induced apoptosis by suppressing oxidative stress, inhibiting MAPKs, and activating the phosphatidylinositol 3-kinase/Akt pathway. © 2017 Yan, Wu, Wu, Hua, Liang, Sun, Yang, Huang and Bian.
Source Title: Frontiers in Pharmacology
URI: https://scholarbank.nus.edu.sg/handle/10635/173871
ISSN: 16639812
DOI: 10.3389/fphar.2017.00007
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