Background： Our previous studies have demonstrated that the levels of 5-hydroxytryptamine （5-HT） and 5-HT 2A receptor （5-HT2AR） in serum and platelet were associated with depression and myocardial infarction （MI...Background： Our previous studies have demonstrated that the levels of 5-hydroxytryptamine （5-HT） and 5-HT 2A receptor （5-HT2AR） in serum and platelet were associated with depression and myocardial infarction （MI）, and pretreatment with ginseng fruit saponins （GFS） before MI and depression had an effect on the 5-HT system. In this study, the effects of GFS on the 5-HT system in the Sprague-Dawley （SD） rats with MI, depression, and MI ＋ depression were evaluated. Methods： A total of eighty SD rats were allocated to four groups： MI, depression, MI ＋ depression, and control groups （n = 20 in each group）. Each group included two subgroups （n = 10 in each subgroup）： Saline treatment subgroup and GFS treatment subgroup. The levels of 5-HT, 5-HT2AR, and serotonin transporter （SERT） were quantified in serum, platelet lysate, and brain tissue through the enzyme-linked immunosorbent assay method, respectively. Results： Compared with those in the saline treatment subgroups, the levels of 5-HT in serum and platelet lysate statistically significantly increased in the GFS treatment subgroups of MI, depression, and MI ＋ depression groups （serum： all P = 0.000; platelet lysate： P = 0.002, 0.000, 0.000, respectively）. However, the 5-HT levels in brain homogenate significantly decreased in the GFS treatment subgroups compared with those in the saline treatment subgroups in MI and depression groups （P = 0.025 and 0.044 respectively）, and no significant difference was observed between saline and GFS treatment subgroups in MI ＋ depression group （P = 0.663）. Compared with that in GFS treatment subgroup of control group, the 5-HT2AR levels in the platelet lysate significantly decreased in GFS treatment subgroups of MI, depression, and MI ＋ depression groups （all P = 0.000）. Compared to those in the saline treatment subgroups, the serum SERT levels significantly decreased in the GFS treatment subgroups in MI, depression, and MI ＋ depression groups （P = 0.009, 0.0展开更多
Colorectal cancer(CRC)is a type of malignant tumor that seriously threatens human health and life,and its treatment has always been a difficulty and hotspot in research.Herein,this study for the first time reports tha...Colorectal cancer(CRC)is a type of malignant tumor that seriously threatens human health and life,and its treatment has always been a difficulty and hotspot in research.Herein,this study for the first time reports that antipsychotic aripiprazole(Ari)against the proliferation of CRC cells both in vitro and in vivo,but with less damage in normal colon cells.Mechanistically,the results showed that5-hydroxytryptamine 2B receptor(HTR2B)and its coupling protein G protein subunit alpha q(Gaq)were highly distributed in CRC cells.Ari had a strong affinity with HTR2B and inhibited HTR2B downstream signaling.Blockade of HTR2B signaling suppressed the growth of CRC cells,but HTR2B was not found to have independent anticancer activity.Interestingly,the binding of Gaq to HTR2B was decreased after Ari treatment.Knockdown of Gaq not only restricted CRC cell growth,but also directly affected the antiCRC efficacy of Ari.Moreover,an interaction between Ari and Gaq was found in that the mutation at amino acid 190 of Gaq reduced the efficacy of Ari.Thus,these results confirm that Gaq coupled to HTR2B was a potential target of Ari in mediating CRC proliferation.Collectively,this study provides a novel effective strategy for CRC therapy and favorable evidence for promoting Ari as an anticancer agent.展开更多
AIM:To investigate serotonergic Ca 2+ signaling and the expression of 5-hydroxytryptamine(5-HT) receptors,as well as Ca 2+ transporting proteins,in hepatic stellate cells(HSCs) . METHODS:The intracellular Ca 2+ concen...AIM:To investigate serotonergic Ca 2+ signaling and the expression of 5-hydroxytryptamine(5-HT) receptors,as well as Ca 2+ transporting proteins,in hepatic stellate cells(HSCs) . METHODS:The intracellular Ca 2+ concentration([Ca 2+ ]i) of isolated rat HSCs was measured with a fluorescence microscopic imaging system.Quantitative PCR was per-formed to determine the transcriptional levels of 5-HT receptors and endoplasmic reticulum(ER) proteins involved in Ca 2+ storage and release in cultured rat HSCs. RESULTS:Distinct from quiescent cells,activated HSCs exhibited[Ca 2+ ]i transients following treatment with 5-HT,which was abolished by U-73122,a phospholipase C inhibitor.Upregulation of 5-HT2A and 5-HT2B receptors,but not 5-HT3,was prominent during trans-differentiation of HSCs.Pretreatment with ritanserin,a 5-HT2 antagonist,inhibited[Ca 2+ ]i changes upon application of 5-HT.Expression of type 1 inositol-5'-triphosphate receptor and type 2 sarcoplasmic/endoplasmic reticulum Ca 2+ ATPase were also increased during activation of HSCs and serve as the major isotypes for ER Ca 2+ storage and release in activated HSCs.Ca 2+ binding chaperone proteins of the ER,including calreticulin,calnexin and calsequestrin,were up-regulated following activation of HSCs. CONCLUSION:The appearance of 5-HT-induced[Ca 2+ ]i response accompanied by upregulation of metabotropic 5-HT2 receptors and Ca 2+ transporting/chaperone ER proteins may participate in the activating process of HSCs.展开更多
文摘Background： Our previous studies have demonstrated that the levels of 5-hydroxytryptamine （5-HT） and 5-HT 2A receptor （5-HT2AR） in serum and platelet were associated with depression and myocardial infarction （MI）, and pretreatment with ginseng fruit saponins （GFS） before MI and depression had an effect on the 5-HT system. In this study, the effects of GFS on the 5-HT system in the Sprague-Dawley （SD） rats with MI, depression, and MI ＋ depression were evaluated. Methods： A total of eighty SD rats were allocated to four groups： MI, depression, MI ＋ depression, and control groups （n = 20 in each group）. Each group included two subgroups （n = 10 in each subgroup）： Saline treatment subgroup and GFS treatment subgroup. The levels of 5-HT, 5-HT2AR, and serotonin transporter （SERT） were quantified in serum, platelet lysate, and brain tissue through the enzyme-linked immunosorbent assay method, respectively. Results： Compared with those in the saline treatment subgroups, the levels of 5-HT in serum and platelet lysate statistically significantly increased in the GFS treatment subgroups of MI, depression, and MI ＋ depression groups （serum： all P = 0.000; platelet lysate： P = 0.002, 0.000, 0.000, respectively）. However, the 5-HT levels in brain homogenate significantly decreased in the GFS treatment subgroups compared with those in the saline treatment subgroups in MI and depression groups （P = 0.025 and 0.044 respectively）, and no significant difference was observed between saline and GFS treatment subgroups in MI ＋ depression group （P = 0.663）. Compared with that in GFS treatment subgroup of control group, the 5-HT2AR levels in the platelet lysate significantly decreased in GFS treatment subgroups of MI, depression, and MI ＋ depression groups （all P = 0.000）. Compared to those in the saline treatment subgroups, the serum SERT levels significantly decreased in the GFS treatment subgroups in MI, depression, and MI ＋ depression groups （P = 0.009, 0.0
基金supported by Chongqing basic research and frontier exploration project(cstc2022ycjh-bgzxm0119,China)。
文摘Colorectal cancer(CRC)is a type of malignant tumor that seriously threatens human health and life,and its treatment has always been a difficulty and hotspot in research.Herein,this study for the first time reports that antipsychotic aripiprazole(Ari)against the proliferation of CRC cells both in vitro and in vivo,but with less damage in normal colon cells.Mechanistically,the results showed that5-hydroxytryptamine 2B receptor(HTR2B)and its coupling protein G protein subunit alpha q(Gaq)were highly distributed in CRC cells.Ari had a strong affinity with HTR2B and inhibited HTR2B downstream signaling.Blockade of HTR2B signaling suppressed the growth of CRC cells,but HTR2B was not found to have independent anticancer activity.Interestingly,the binding of Gaq to HTR2B was decreased after Ari treatment.Knockdown of Gaq not only restricted CRC cell growth,but also directly affected the antiCRC efficacy of Ari.Moreover,an interaction between Ari and Gaq was found in that the mutation at amino acid 190 of Gaq reduced the efficacy of Ari.Thus,these results confirm that Gaq coupled to HTR2B was a potential target of Ari in mediating CRC proliferation.Collectively,this study provides a novel effective strategy for CRC therapy and favorable evidence for promoting Ari as an anticancer agent.
基金Supported by Grants from the Korean National Research Foun-dation(2010-0014617)the Myung Sun Kim Memorial Founda-tion(2009)the Yonsei University Faculty Research Grant(2004)
文摘AIM:To investigate serotonergic Ca 2+ signaling and the expression of 5-hydroxytryptamine(5-HT) receptors,as well as Ca 2+ transporting proteins,in hepatic stellate cells(HSCs) . METHODS:The intracellular Ca 2+ concentration([Ca 2+ ]i) of isolated rat HSCs was measured with a fluorescence microscopic imaging system.Quantitative PCR was per-formed to determine the transcriptional levels of 5-HT receptors and endoplasmic reticulum(ER) proteins involved in Ca 2+ storage and release in cultured rat HSCs. RESULTS:Distinct from quiescent cells,activated HSCs exhibited[Ca 2+ ]i transients following treatment with 5-HT,which was abolished by U-73122,a phospholipase C inhibitor.Upregulation of 5-HT2A and 5-HT2B receptors,but not 5-HT3,was prominent during trans-differentiation of HSCs.Pretreatment with ritanserin,a 5-HT2 antagonist,inhibited[Ca 2+ ]i changes upon application of 5-HT.Expression of type 1 inositol-5'-triphosphate receptor and type 2 sarcoplasmic/endoplasmic reticulum Ca 2+ ATPase were also increased during activation of HSCs and serve as the major isotypes for ER Ca 2+ storage and release in activated HSCs.Ca 2+ binding chaperone proteins of the ER,including calreticulin,calnexin and calsequestrin,were up-regulated following activation of HSCs. CONCLUSION:The appearance of 5-HT-induced[Ca 2+ ]i response accompanied by upregulation of metabotropic 5-HT2 receptors and Ca 2+ transporting/chaperone ER proteins may participate in the activating process of HSCs.
