The New Synthetic H(2)S-Releasing SDSS Protects MC3T3-E1 Osteoblasts against H(2)O(2)-Induced Apoptosis by Suppressing Oxidative Stress, Inhibiting MAPKs, and Activating the PI3K/Akt Pathway.
The New Synthetic H(2)S-Releasing SDSS Protects MC3T3-E1 Osteoblasts against H(2)O(2)-Induced Apoptosis by Suppressing Oxidative Stress, Inhibiting MAPKs, and Activating the PI3K/Akt Pathway.
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新的合成H（2）S-释放SDSS通过抑制氧化应激，抑制MAPK并激活PI3K/AKT途径，可以保护MC3T3-E1成骨细胞免受H（2）O（2）O（2）O（2）O（2）O（2）O（2）O（2）O（2）O（2）O（2）O（2）O（2）O（2）O（2）O（2）O（2）O（2）o释放SDSS抑制新合成H（2）O（通过抑制氧化员诱导的细胞凋亡员）来保护MC3T3-O（2））通过抑制氧化员诱导的凋代的h（2））通过抑制氧化员诱导的细院来保护新的合员H（2），从而通过抑制MAP，可以通过激活PI3K）
DOI：
10.3389/fphar.2017.00007
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发表时间：
2017
影响因子：
5.6
通讯作者：
Bian JS
中科院分区：
文献类型：
--
作者：
Yan X;Wu H;Wu Z;Hua F;Liang D;Sun H;Yang Y;Huang D;Bian JS
活性氧(ROS)在骨质疏松症的发生发展中起着重要作用。氧化应激诱导成骨细胞凋亡并阻止其分化。丹参素(DSS)和硫化氢(H_2S)在不同的体系中都有明显的抗氧化作用。在本研究中，我们合成了一种来源于DSS的新型硫化氢释放化合物SDSS，并研究了其在过氧化氢诱导的MC3T3-E1成骨细胞损伤模型中的抗氧化作用。我们首次在体内和体外模型中表征了SDSS的硫化氢释放特性。结果表明，成年大鼠静脉注射SDSS可在几分钟内释放出大鼠血浆中已证实的H_2S缓释部分ADT-OH。利用硫化氢选择性荧光探针，我们进一步证实了SDSS在MC3T3-E1成骨细胞中释放了硫化氢。生物学研究表明，SDSS对H_2O_2诱导的MC3T3-E1细胞凋亡无明显毒性作用，但具有保护作用。SDSS还逆转了过氧化氢诱导的细胞分化停滞。这是由于SDSS对骨涎蛋白、矮小相关转录因子2、胶原表达、碱性磷酸酶活性和骨结节形成的刺激作用所致。进一步的研究表明，SDSS逆转了过氧化氢处理的细胞超氧化物歧化酶活性和谷胱甘肽含量的降低以及ROS产生的增加。此外，SDSS还显著减弱了H_2O_2诱导的p38-、ERK1/2-和JNK-MAPKs的激活。SDSS还可激活磷脂酰肌醇3-激酶/Akt信号通路。阻断该通路可减弱SDSS的细胞保护作用。综上所述，SDSS通过抑制氧化应激，抑制MAPKs，激活磷脂酰肌醇3-激酶/Akt通路，保护MC3T3-E1细胞免受过氧化氢诱导的细胞凋亡。
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.