Oxidative stress induces apoptosis of many cells and arrest of their differentiation.Both Danshensu(DSS) and hydrogen sulfide(H_2S) produce significant antioxidant effect in various systems.In this study,we synthesize...Oxidative stress induces apoptosis of many cells and arrest of their differentiation.Both Danshensu(DSS) and hydrogen sulfide(H_2S) produce significant antioxidant effect in various systems.In this study,we synthesized SDSS,a new H_2S-releasing compound derived from DSS,and studied its antioxidant effect in an H_2O_2-induced MC3T3-E1 osteoblastic cell injury model.We first characterized the H_2S 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 H_2S sustained-release moiety,within several minutes in the rat plasma.Using an H_2S selective fluorescent probe,we further confirmed that SDSS released H_2S in MC3T3-E1 osteoblastic cells.Biological studies revealed that SDSS had no significant toxic effect but produced protective effects against H_2O_2-induced MC3T3-E1 cell apoptosis.SDSS also reversed the arrest of cell differentiation caused by H_2O_2 treatment.This was caused by the stimulatory effect of SDSS on bone sialo protein,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 H_2O_2 treated cells.In addition,SDSS significantly attenuated H_2O_2-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.We also observed the effect of SDSS on aspirin-induced gastric injury and found that SDSS protected against aspirin-induced gastric damage.In conclusion,SDSS protects cells against H_2O_2-induced apoptosis by suppressing oxidative stress.展开更多
Pulmonary hypertension(PH)is an extremely malignant pulmonary vascular disease of unknown etiology.ADAR1 is an RNA editing enzyme that converts adenosine in RNA to inosine,thereby affecting RNA expression.However,the ...Pulmonary hypertension(PH)is an extremely malignant pulmonary vascular disease of unknown etiology.ADAR1 is an RNA editing enzyme that converts adenosine in RNA to inosine,thereby affecting RNA expression.However,the role of ADAR1 in PH development remains unclear.In the present study,we investigated the biological role and molecular mechanism of ADAR1 in PH pulmonary vascular remodeling.Overexpression of ADAR1 aggravated PH progression and promoted the proliferation of pulmonary artery smooth muscle cells(PASMCs).Conversely,inhibition of ADAR1 produced opposite effects.High-throughput whole transcriptome sequencing showed that ADAR1 was an important regulator of circRNAs in PH.CircCDK17 level was significantly lowered in the serum of PH patients.The effects of ADAR1 on cell cycle progression and proliferation were mediated by circCDK17.ADAR1 affects the stability of circCDK17 by mediating A-to-I modification at the A5 and A293 sites of circCDK17 to prevent it from mlA modification.We demonstrate for the first time that ADAR1 contributes to the PH development,at least partially,through m1A modification of circCDK17 and the subsequent PASMCs proliferation.Our study provides a novel therapeutic strategy for treatment of PH and the evidence for circCDK17 as a potential novel marker for the diagnosis of this disease.展开更多
Dear Editor,Cerebral ischemic stroke is one of the leading causes of death worldwide with no effective treatment methods.Therefore,the investigation of potential intervention targets is urgently needed.Na^(+)/K^(+)-AT...Dear Editor,Cerebral ischemic stroke is one of the leading causes of death worldwide with no effective treatment methods.Therefore,the investigation of potential intervention targets is urgently needed.Na^(+)/K^(+)-ATPase(NKA),a well-studied transmembrane protein pump expressed in all cells,is essential for the maintenance of cell membrane potential by exchanging three sodium ions out with two potassium ions into the cell to strictly regulate the electrochemical gradient and hence neuronal excitability.The energy demand of NKA-mediated maintenance of the membrane potential is~40%of the energy produced by respiration in the brain.1 NKAα1 is ubiquitously expressed and important for ion gradient maintenance.Preservation of the function of NKAα1 was recently reported to relieve ischemic damage.展开更多
文摘Oxidative stress induces apoptosis of many cells and arrest of their differentiation.Both Danshensu(DSS) and hydrogen sulfide(H_2S) produce significant antioxidant effect in various systems.In this study,we synthesized SDSS,a new H_2S-releasing compound derived from DSS,and studied its antioxidant effect in an H_2O_2-induced MC3T3-E1 osteoblastic cell injury model.We first characterized the H_2S 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 H_2S sustained-release moiety,within several minutes in the rat plasma.Using an H_2S selective fluorescent probe,we further confirmed that SDSS released H_2S in MC3T3-E1 osteoblastic cells.Biological studies revealed that SDSS had no significant toxic effect but produced protective effects against H_2O_2-induced MC3T3-E1 cell apoptosis.SDSS also reversed the arrest of cell differentiation caused by H_2O_2 treatment.This was caused by the stimulatory effect of SDSS on bone sialo protein,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 H_2O_2 treated cells.In addition,SDSS significantly attenuated H_2O_2-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.We also observed the effect of SDSS on aspirin-induced gastric injury and found that SDSS protected against aspirin-induced gastric damage.In conclusion,SDSS protects cells against H_2O_2-induced apoptosis by suppressing oxidative stress.
基金supported by the National Natural Science Foundation of China(NSFC),China(Grant No 82170064,82241021 to Xiaowei Nie)Shenzhen Excellent Science and Technology Innovation Talent Development Programme,Shenzhen,China(Grant No.RCJC20210706091946002 to Xiaowei Nie)+1 种基金Shenzhen Science and Technology Program,Shenzhen,China(Grant No.JSGGZD20220822095200001 to Jin-Song Bian)China Postdoctoral Science Foundation,China(Grant No.2022M722212 to Junting Zhang).
文摘Pulmonary hypertension(PH)is an extremely malignant pulmonary vascular disease of unknown etiology.ADAR1 is an RNA editing enzyme that converts adenosine in RNA to inosine,thereby affecting RNA expression.However,the role of ADAR1 in PH development remains unclear.In the present study,we investigated the biological role and molecular mechanism of ADAR1 in PH pulmonary vascular remodeling.Overexpression of ADAR1 aggravated PH progression and promoted the proliferation of pulmonary artery smooth muscle cells(PASMCs).Conversely,inhibition of ADAR1 produced opposite effects.High-throughput whole transcriptome sequencing showed that ADAR1 was an important regulator of circRNAs in PH.CircCDK17 level was significantly lowered in the serum of PH patients.The effects of ADAR1 on cell cycle progression and proliferation were mediated by circCDK17.ADAR1 affects the stability of circCDK17 by mediating A-to-I modification at the A5 and A293 sites of circCDK17 to prevent it from mlA modification.We demonstrate for the first time that ADAR1 contributes to the PH development,at least partially,through m1A modification of circCDK17 and the subsequent PASMCs proliferation.Our study provides a novel therapeutic strategy for treatment of PH and the evidence for circCDK17 as a potential novel marker for the diagnosis of this disease.
基金supported by Singapore National Medical Research Council research grants(CIRG/1432/2015)the National Natural Science Foundation of China(NSFC 81872865).
文摘Dear Editor,Cerebral ischemic stroke is one of the leading causes of death worldwide with no effective treatment methods.Therefore,the investigation of potential intervention targets is urgently needed.Na^(+)/K^(+)-ATPase(NKA),a well-studied transmembrane protein pump expressed in all cells,is essential for the maintenance of cell membrane potential by exchanging three sodium ions out with two potassium ions into the cell to strictly regulate the electrochemical gradient and hence neuronal excitability.The energy demand of NKA-mediated maintenance of the membrane potential is~40%of the energy produced by respiration in the brain.1 NKAα1 is ubiquitously expressed and important for ion gradient maintenance.Preservation of the function of NKAα1 was recently reported to relieve ischemic damage.
