Object: The authors studied the influence of CO2 pneumoperitoneum on intracellular pH and signal transduction arising from cancer cell multiplication in laparoscopic tumor operation. Method: They set up a simulation o...Object: The authors studied the influence of CO2 pneumoperitoneum on intracellular pH and signal transduction arising from cancer cell multiplication in laparoscopic tumor operation. Method: They set up a simulation of pneumoperitoneum under different CO2 pressure, and then measured the variation of intracellular pH (pHi) at different time and the activity of protein kinase C (PKC) and protein phosphatase 2a (PP2a) at the end of the pneumoperitoneum. After 1 week, the concentration of cancer cells in the culture medium was calculated. Result: When the pressure of CO2 pneumoperitoneum was 0, 10, 20, 30 mmHg respectively, the average pHi was 7.273, 7.075, 6.783, 6.693 at the end of the pneumoperitoneum; PKC activity was 159.4, 168.5,178.0, 181.6 nmol/(g.min) and PP2a was 4158.3, 4066.9, 3984.0, 3878.5 nmol/(g.min) respectively. After 1 week, the cancer cells concentration was 2.15×105, 2.03×105, 2.20×105, 2.18×105 L-1. Conclusion: CO2 pneumoperitoneum could promote acidosis in cancer cells, inducing the activation of protein kinase C and deactivation of protein phosphatase 2a, but it could not accelerate the mitosis rate of the cancer cells.展开更多
In the present study, a rat model of type 2 diabetes mellitus was established by continuous peritoneal injection of streptozotocin. Following intragastric perfusion of sericin for 35 days, blood glucose levels signifi...In the present study, a rat model of type 2 diabetes mellitus was established by continuous peritoneal injection of streptozotocin. Following intragastric perfusion of sericin for 35 days, blood glucose levels significantly reduced, neuronal apoptosis in the hippocampal CA1 region decreased, hippocampal phosphorylated Akt and nuclear factor kappa B expression were enhanced, but Bcl-xL/Bcl-2 associated death promoter expression decreased. Results demonstrated that sericin can reduce hippocampal neuronal apoptosis in a rat model of diabetes mellitus by regulating abnormal changes in the Akt signal transduction pathway.展开更多
AIM:To construct the CABYR RNAi plasmid and study its relation with the nuclear factor(NF)-κB signal transduction pathway.METHODS:Human CABYR mRNA sequence was obtained from GenBank.The structure of cDNA sequence for...AIM:To construct the CABYR RNAi plasmid and study its relation with the nuclear factor(NF)-κB signal transduction pathway.METHODS:Human CABYR mRNA sequence was obtained from GenBank.The structure of cDNA sequence for the short hairpin RNA was BbsⅠ+sense+loop+ antisense+transcription terminator+KpnⅠ+Bam HⅠ.A CABYR silencing plasmid was constructed and transfected into the human embryo cell line 293T.Quantitative real-time polymerase chain reaction was used to analyze CABYR and NF-κB gene expression.RESULTS:The CABYR and NF-κB expressions were detected in 293T cells.The oligonucleotide(5'-GCT-CAGATGTTAGGTAAAG-3')efficiently silenced the expression of CABYR.The expression of NF-κB was not significantly affected by silencing CABYR(P=0.743).CONCLUSION:CABYR can be found in the human embryo cell line 293T.Cabyrmid 2 can efficiently silence its target,CABYR,indicating that CABYR is not related with the NF-κB signal transduction pathway.展开更多
Objective: To investigate the effect of MEK1 inhibitor PD98058 on Tec and ERK2 in HepG2 hepatoma cells. Methods: The expression of mRNA and protein of Tec and ERK2 in HepG2 cells was detected by immunocytochemistry as...Objective: To investigate the effect of MEK1 inhibitor PD98058 on Tec and ERK2 in HepG2 hepatoma cells. Methods: The expression of mRNA and protein of Tec and ERK2 in HepG2 cells was detected by immunocytochemistry as- say. After various concentration of PD98059 treatment, the expression of Tec and ERK2 mRNA in HepG2 cells was detected by RT-PCR and Western blotting. Results: Tec and ERK2 expressed highly in HepG2 cells. PD98059 obviously inhibited the expression of mRNA and protein of Tec and ERK2 in a dose-dependent manner, in which 40 μmol/L of PD98059 exhibited the strongest inhibiting effect. Conclusion: PD98058, as MEK1 inhibitor, can inhibit Tec, block the signal route of Ras/Raf/ERK and to impede the signal transduction in HepG2 cells. Tec may be the signal protein in the upper stream of Ras/Raf/ERK in hepatocarcinoma cells and is supposed to interact with the signal way of Ras/Raf/ERK.展开更多
目的研究通痹颗粒对胶原诱导性关节炎(collagen-induced arthritis,CIA)大鼠铁调素(hepcidin,Hepc)、Janus激酶(janus kinase,JAK)2/信号转导子和转录激活子(signal transduction and activator of transcription,STAT)3信号通路的影响...目的研究通痹颗粒对胶原诱导性关节炎(collagen-induced arthritis,CIA)大鼠铁调素(hepcidin,Hepc)、Janus激酶(janus kinase,JAK)2/信号转导子和转录激活子(signal transduction and activator of transcription,STAT)3信号通路的影响。方法选取36只雌性SD大鼠随机分成空白组、模型组、阳性对照组和通痹颗粒低、中、高剂量组,每组6只。空白组不予处理,其余组用牛Ⅱ型胶原建立CIA模型。造模完成后,空白组、模型组予生理盐水灌胃,其余各组分别以巴瑞替尼片和低、中、高剂量通痹颗粒灌胃。每天1次,连续4周。HE染色行滑膜组织病理学观察;酶联免疫吸附法测定血清Hepc、白细胞介素6(interleukin 6,IL-6)水平;逆转录-聚合酶链反应法测定滑膜中JAK2、STAT3、细胞信号因子传导抑制体(suppressor of cytokine signaling,SOCS)1、SOCS3的mRNA相对表达量;Western blot法检测滑膜中JAK2、p-JAK2、STAT3、p-STAT3、SOCS1、SOCS3的蛋白表达量。结果模型组见滑膜上皮结构缺损,滑膜重度增生,排列紊乱,并有大量炎症细胞浸润和多个血管翳形成;各给药组滑膜炎症均有所减轻,阳性对照组优于通痹颗粒高剂量组,通痹颗粒中、高剂量组优于低剂量组。与模型组相比,各给药组关节炎指数评分、血清Hepc和IL-6水平均显著降低(P<0.01);与阳性对照组相比,通痹颗粒中、低剂量组关节炎指数评分、血清Hepc和IL-6水平均升高(P<0.05)。与模型组比较,阳性对照组和通痹颗粒低、中、高剂量组JAK2、STAT3 mRNA和蛋白以及p-JAK2、p-STAT3的蛋白表达量均降低(P<0.05),而通路抑制因子SOCS1、SOCS3 mRNA和蛋白的表达均升高(P<0.05);与阳性对照组比较,通痹颗粒各剂量组JAK2、STAT3 mRNA和蛋白以及p-JAK2、p-STAT3的蛋白表达量均升高(P<0.05),而SOCS1、SOCS3 mRNA和蛋白的表达均降低(P<0.05)。结论通痹颗粒能够改善CIA大鼠滑膜炎症,其机制可能与抑制JAK2/STAT3信号通路而减少Hepc的表达有关。展开更多
Soluble sugars function not only as the energy and structural blocks supporting plants,but also as osmoregulators and signal molecules during plant adaptation to water deficit.Here,we investigated drought resistance i...Soluble sugars function not only as the energy and structural blocks supporting plants,but also as osmoregulators and signal molecules during plant adaptation to water deficit.Here,we investigated drought resistance in transgenic apple(Malus×domestica)overexpressing MdFRK2,a key gene regulating fructose content and sugar metabolism.There is no obvious phenotypic difference between MdFRK2-overexpressing transgenic plants and WT plants under the well-watered condition.However,the transgenic plants and the grafted plants using MdFRK2-overexpressing rootstock exhibited improved tolerance to drought stress.Overexpression of MdFRK2 significantly promoted the growth of root system under drought stress.RNA sequencing showed that under drought stress,genes involved in sugar metabolism,transcription regulation,signal transduction or hormone metabolism were differentially expressed in MdFRK2 transgenic plants.Consistent with the gene expression profile,the activities of enzyme(SDH,FRK and NI)involved in sugar metabolism in the roots of MdFRK2 transgenic plants were significantly higher than those of untransformed control plants after drought stress.Under drought stress,overexpression of MdFRK2 promoted the accumulation of IAA,and decreased the contents of ABA and CK in apple root system.In conclusion,these results suggest that MdFRK2 can promote the growth of apple roots under drought stress by regulating sugar metabolism and accumulation,hormone metabolism and signal transduction,and then resist drought stress.展开更多
Cellular biological activities are tightly controlled by intracellular signaling processes initiated by extracellular signals. Protein tyrosine phosphatases, which remove phosphate groups from phosphorylated signaling...Cellular biological activities are tightly controlled by intracellular signaling processes initiated by extracellular signals. Protein tyrosine phosphatases, which remove phosphate groups from phosphorylated signaling molecules, play equally important tyrosine roles as protein tyrosine kinases in signal transduction. SHP-2, a cytoplajsmic SH2 domain containing protein tyrosine phosphatase, is involved in the signaling pathways of a variety of growth factors and cytokines. Recent studies have clearly demonstrated that this phosphatase plays an important role in transducing signal relay from the cell surface to the nucleus, and is a critical intracellular regulator in mediating cell proliferation and differentiation.展开更多
The role of inositol 1,4,5-trisphosphate （IP3） in transducing heat-shock （HS） signals was examined in Arabidopsis. The whole-plant IP3 level increased within 1 min of HS at 37℃. After 3 min of HS, the IP3 level r...The role of inositol 1,4,5-trisphosphate （IP3） in transducing heat-shock （HS） signals was examined in Arabidopsis. The whole-plant IP3 level increased within 1 min of HS at 37℃. After 3 min of HS, the IP3 level reached a maximum 2.5 fold increase. Using the transgenic Arabidopsis plants that have AtHsp 18.2 promoter-β-glucuronidase （GUS） fusion gene, it was found that the level of GUS activity was up-regulated by the addition of caged IP3 at both non-HS and HS temperatures and was down-regulated by the phospholipase C （PLC） inhibitors {1-[6-（（ 1713-3-Methoxyestra-1,3,5（10）-trien- 7-yl）amino）hexyl]-2,5-pyrrolidinedione } （U-73122）. The intracellular-free calcium ion concentration （[Ca^2＋]i） increased during HS at 37℃ in suspension-cultured Arabidopsis cells expressing apoaequorin. Treatment with U-73122 prevented the increase of [Ca^2＋]i to some extent. Above results provided primary evidence for the possible involvement of IP3 in HS signal transduction in higher plants.展开更多
Detailed mechanisms behind regeneration after nerve injury, in particular signal transduction and the fate of Schwann cells （SCs）, are poorly understood. Here, we investigated axotomy-induced activation of extracell...Detailed mechanisms behind regeneration after nerve injury, in particular signal transduction and the fate of Schwann cells （SCs）, are poorly understood. Here, we investigated axotomy-induced activation of extracellular- signal-regulated kinase-1/2 （ERK1/2; important for proliferation） and m-calpain in vitro, and the relation to Ca2＋ deletion and Schwann cell proliferation and death after rat sciatic nerve axotomy. Nerve segments were cultured for up to 72 hours with and without ethylene glycol-bis（β-aminoethyl ether）- N,N,N＇,N＇-tetraacetic acid （EGTA）. In some experiments, 5-bromo-2′-deoxyuridine （BrdU） was added during the last 24 hours to detect proliferating cells and propidium iodide （PI） was added at the last hour to detect dead and/or dying cells. Immunohistochemistry of sections of the cultured nerve segments was performed to label m-calpain and the phosphorylated and activated form of ERK1/2. The experiments revealed that immunoreactivity for p-ERK1/2 increased with time in organotypically cultured SCs. p-ERK1/2 and m-calpain were also observed in axons. A significant increase in the number of dead or dying SCs was observed in nerve segments cultured for 24 hours. When deprived of Ca2＋, activation of axonal m-calpain was reduced, whereas p-ERK1/2 was increased in SCs. Ca2＋ deprivation also significantly reduced the number of proliferating SCs, and instead increased the number of dead or dying SCs. Ca2＋ seems to play an important role in activation of ERK1/2 in SCs and in SC survival and proliferation. In addition, extracellular Ca2＋ levels are also required for m-calpain activation and up-regulation in axons. Thus, regulation of Ca2＋ levels is likely to be a useful method to promote SC proliferation.展开更多
AIM： To explore the mechanism for interactions of leptin with ghrelin and orexin in the arcuate nucleus （ARC） activating neuropeptide Y （NPY） neurons during physiological regulation of feeding, METHODS： Single n...AIM： To explore the mechanism for interactions of leptin with ghrelin and orexin in the arcuate nucleus （ARC） activating neuropeptide Y （NPY） neurons during physiological regulation of feeding, METHODS： Single neurons from ARC of adult rats with matured feeding function were isolated. [Ca2＋]i was measured to monitore their activities. The time course of leptin effects on ghrelin-induced versus orexin-induced [Ca2＋]i increases in NPY neurons was studied. RESULTS： Administration of ghrelin or orexin-A at 101~ mol/L increased cytosolic Ca2~ concentration （[Ca2＋]~） in NPY neurons isolated from the ARC of adult rats. Upon administration of leptin at 10^-14-10^-12 mol/L, ghrelin-induced [Ca2＋]i increases were initially （〈 10 min） inhibited but later restored, exhibiting a transient pattern of inhibition. In contrast, orexin-induced [Ca2＋]i increases were inhibited by leptin in a long- lasting manner. Furthermore, a prior administration of leptin inhibited orexin action but not ghrelin action to increase ICa 2＋li, CONCLUSION： Leptin counteracted ghrelin effects transiently and orexin effects long-lastingly in NPY neurons. The transient property with which leptin counteracts ghrelin action in NPY neurons may allow the fasting-associated increase in ghrelin levels to activate NPY neurons in the presence of physiological leptin and to stimulate feeding.展开更多
A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and forms a multifunctional transducing organ that mediates a plethora of cardiovascular processes. The activation of ECs from as state of quiesc...A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and forms a multifunctional transducing organ that mediates a plethora of cardiovascular processes. The activation of ECs from as state of quiescence is, therefore, regarded among the early events leading to the onset and progression of potentially lethal diseases, such as hypertension, myocardial infarction, brain stroke, and tumor. Intracellular Ca2+ signals have long been know to play a central role in the complex network of signaling pathways regulating the endothelial functions. Notably, recent work has outlined how any change in the pattern of expression of endothelial channels, transporters and pumps involved in the modulation of intracellular Ca2+ levels may dramatically affect whole body homeostasis. Vascular ECs may react to both mechanical and chemical stimuli by generating a variety of intracellular Ca2+ signals, ranging from brief, localized Ca2+ pulses to prolonged Ca2+ oscillations engulfing the whole cytoplasm. The well-defined spatiotemporal profile of the subcellular Ca2+ signals elicited in ECs by specific extracellular inputs depends on the interaction between Ca2+ releasing channels, which arelocated both on the plasma membrane and in a number of intracellular organelles, and Ca2+ removing systems. The present article aims to summarize both the past and recent literature in the field to provide a clear-cut picture of our current knowledge on the molecular nature and the role played by the components of the Ca2+ machinery in vascular ECs under both physiological and pathological conditions.展开更多
基金Project supported by Research and Development Funds of Second Affiliated Hospital, School of Medicine, Zhejiang University, China
文摘Object: The authors studied the influence of CO2 pneumoperitoneum on intracellular pH and signal transduction arising from cancer cell multiplication in laparoscopic tumor operation. Method: They set up a simulation of pneumoperitoneum under different CO2 pressure, and then measured the variation of intracellular pH (pHi) at different time and the activity of protein kinase C (PKC) and protein phosphatase 2a (PP2a) at the end of the pneumoperitoneum. After 1 week, the concentration of cancer cells in the culture medium was calculated. Result: When the pressure of CO2 pneumoperitoneum was 0, 10, 20, 30 mmHg respectively, the average pHi was 7.273, 7.075, 6.783, 6.693 at the end of the pneumoperitoneum; PKC activity was 159.4, 168.5,178.0, 181.6 nmol/(g.min) and PP2a was 4158.3, 4066.9, 3984.0, 3878.5 nmol/(g.min) respectively. After 1 week, the cancer cells concentration was 2.15×105, 2.03×105, 2.20×105, 2.18×105 L-1. Conclusion: CO2 pneumoperitoneum could promote acidosis in cancer cells, inducing the activation of protein kinase C and deactivation of protein phosphatase 2a, but it could not accelerate the mitosis rate of the cancer cells.
基金supported by a grant from the Education Department of Hebei Province (Mechanism of GH/IGF-1 and protective effects of sericin on gonadal axis lesions in diabetes mellitus), No. 2006301a grant from Science and Technology Department of Hebei Province (Protective effects of sericin on testicular dysfunction in diabetes mellitus), No. 08276101D-19
文摘In the present study, a rat model of type 2 diabetes mellitus was established by continuous peritoneal injection of streptozotocin. Following intragastric perfusion of sericin for 35 days, blood glucose levels significantly reduced, neuronal apoptosis in the hippocampal CA1 region decreased, hippocampal phosphorylated Akt and nuclear factor kappa B expression were enhanced, but Bcl-xL/Bcl-2 associated death promoter expression decreased. Results demonstrated that sericin can reduce hippocampal neuronal apoptosis in a rat model of diabetes mellitus by regulating abnormal changes in the Akt signal transduction pathway.
基金Supported by Grants from Natural Science Foundation of China, No.30940034
文摘AIM:To construct the CABYR RNAi plasmid and study its relation with the nuclear factor(NF)-κB signal transduction pathway.METHODS:Human CABYR mRNA sequence was obtained from GenBank.The structure of cDNA sequence for the short hairpin RNA was BbsⅠ+sense+loop+ antisense+transcription terminator+KpnⅠ+Bam HⅠ.A CABYR silencing plasmid was constructed and transfected into the human embryo cell line 293T.Quantitative real-time polymerase chain reaction was used to analyze CABYR and NF-κB gene expression.RESULTS:The CABYR and NF-κB expressions were detected in 293T cells.The oligonucleotide(5'-GCT-CAGATGTTAGGTAAAG-3')efficiently silenced the expression of CABYR.The expression of NF-κB was not significantly affected by silencing CABYR(P=0.743).CONCLUSION:CABYR can be found in the human embryo cell line 293T.Cabyrmid 2 can efficiently silence its target,CABYR,indicating that CABYR is not related with the NF-κB signal transduction pathway.
基金Supported by grants from the National Natural Science Foundation of China (No. 30370341, 30570410)the Academic Foundation for Au-thors of National Excellent Doctoral Dissertation of China (No. 200261).
文摘Objective: To investigate the effect of MEK1 inhibitor PD98058 on Tec and ERK2 in HepG2 hepatoma cells. Methods: The expression of mRNA and protein of Tec and ERK2 in HepG2 cells was detected by immunocytochemistry as- say. After various concentration of PD98059 treatment, the expression of Tec and ERK2 mRNA in HepG2 cells was detected by RT-PCR and Western blotting. Results: Tec and ERK2 expressed highly in HepG2 cells. PD98059 obviously inhibited the expression of mRNA and protein of Tec and ERK2 in a dose-dependent manner, in which 40 μmol/L of PD98059 exhibited the strongest inhibiting effect. Conclusion: PD98058, as MEK1 inhibitor, can inhibit Tec, block the signal route of Ras/Raf/ERK and to impede the signal transduction in HepG2 cells. Tec may be the signal protein in the upper stream of Ras/Raf/ERK in hepatocarcinoma cells and is supposed to interact with the signal way of Ras/Raf/ERK.
基金supported by the National Natural Science Foundation of China(Grant No.32001988)the National Natural Science Foundation of Shaanxi Province(Grant No.2020JC-21)+1 种基金the Open Project Program of State Key Laboratory of Crop Stress Biology for Arid Areas(Grant No.CSBAA2020002)the earmarked fund for the China Agriculture Research System(Grant No.CARS-27)。
文摘Soluble sugars function not only as the energy and structural blocks supporting plants,but also as osmoregulators and signal molecules during plant adaptation to water deficit.Here,we investigated drought resistance in transgenic apple(Malus×domestica)overexpressing MdFRK2,a key gene regulating fructose content and sugar metabolism.There is no obvious phenotypic difference between MdFRK2-overexpressing transgenic plants and WT plants under the well-watered condition.However,the transgenic plants and the grafted plants using MdFRK2-overexpressing rootstock exhibited improved tolerance to drought stress.Overexpression of MdFRK2 significantly promoted the growth of root system under drought stress.RNA sequencing showed that under drought stress,genes involved in sugar metabolism,transcription regulation,signal transduction or hormone metabolism were differentially expressed in MdFRK2 transgenic plants.Consistent with the gene expression profile,the activities of enzyme(SDH,FRK and NI)involved in sugar metabolism in the roots of MdFRK2 transgenic plants were significantly higher than those of untransformed control plants after drought stress.Under drought stress,overexpression of MdFRK2 promoted the accumulation of IAA,and decreased the contents of ABA and CK in apple root system.In conclusion,these results suggest that MdFRK2 can promote the growth of apple roots under drought stress by regulating sugar metabolism and accumulation,hormone metabolism and signal transduction,and then resist drought stress.
文摘Cellular biological activities are tightly controlled by intracellular signaling processes initiated by extracellular signals. Protein tyrosine phosphatases, which remove phosphate groups from phosphorylated signaling molecules, play equally important tyrosine roles as protein tyrosine kinases in signal transduction. SHP-2, a cytoplajsmic SH2 domain containing protein tyrosine phosphatase, is involved in the signaling pathways of a variety of growth factors and cytokines. Recent studies have clearly demonstrated that this phosphatase plays an important role in transducing signal relay from the cell surface to the nucleus, and is a critical intracellular regulator in mediating cell proliferation and differentiation.
基金This work was supported by the National Natural Science Foundation of China （No. 30270796） Natural Science Foundation of Hebei Province, China （No. C2005000171）.
文摘The role of inositol 1,4,5-trisphosphate （IP3） in transducing heat-shock （HS） signals was examined in Arabidopsis. The whole-plant IP3 level increased within 1 min of HS at 37℃. After 3 min of HS, the IP3 level reached a maximum 2.5 fold increase. Using the transgenic Arabidopsis plants that have AtHsp 18.2 promoter-β-glucuronidase （GUS） fusion gene, it was found that the level of GUS activity was up-regulated by the addition of caged IP3 at both non-HS and HS temperatures and was down-regulated by the phospholipase C （PLC） inhibitors {1-[6-（（ 1713-3-Methoxyestra-1,3,5（10）-trien- 7-yl）amino）hexyl]-2,5-pyrrolidinedione } （U-73122）. The intracellular-free calcium ion concentration （[Ca^2＋]i） increased during HS at 37℃ in suspension-cultured Arabidopsis cells expressing apoaequorin. Treatment with U-73122 prevented the increase of [Ca^2＋]i to some extent. Above results provided primary evidence for the possible involvement of IP3 in HS signal transduction in higher plants.
基金supported by the Research School in Pharmaceutical Science in Lund,The Royal Physiographic Society in LundThe Swedish Research Council(Medicine)+1 种基金the Craaford’s and Thure Nilsson’s Funds for Medical ResearchFunds for diabetic research,Lund University and Region Skane
文摘Detailed mechanisms behind regeneration after nerve injury, in particular signal transduction and the fate of Schwann cells （SCs）, are poorly understood. Here, we investigated axotomy-induced activation of extracellular- signal-regulated kinase-1/2 （ERK1/2; important for proliferation） and m-calpain in vitro, and the relation to Ca2＋ deletion and Schwann cell proliferation and death after rat sciatic nerve axotomy. Nerve segments were cultured for up to 72 hours with and without ethylene glycol-bis（β-aminoethyl ether）- N,N,N＇,N＇-tetraacetic acid （EGTA）. In some experiments, 5-bromo-2′-deoxyuridine （BrdU） was added during the last 24 hours to detect proliferating cells and propidium iodide （PI） was added at the last hour to detect dead and/or dying cells. Immunohistochemistry of sections of the cultured nerve segments was performed to label m-calpain and the phosphorylated and activated form of ERK1/2. The experiments revealed that immunoreactivity for p-ERK1/2 increased with time in organotypically cultured SCs. p-ERK1/2 and m-calpain were also observed in axons. A significant increase in the number of dead or dying SCs was observed in nerve segments cultured for 24 hours. When deprived of Ca2＋, activation of axonal m-calpain was reduced, whereas p-ERK1/2 was increased in SCs. Ca2＋ deprivation also significantly reduced the number of proliferating SCs, and instead increased the number of dead or dying SCs. Ca2＋ seems to play an important role in activation of ERK1/2 in SCs and in SC survival and proliferation. In addition, extracellular Ca2＋ levels are also required for m-calpain activation and up-regulation in axons. Thus, regulation of Ca2＋ levels is likely to be a useful method to promote SC proliferation.
基金Supported by Grant-in-Aid for Scientific Research (B) (18390065, 20390061) that on Priority Areas (15081101) from Japan Society for the Promotion of Science (JSPS)+2 种基金a grant from the 21st century Center of Excellence (COE) program, an Insulin Research Award from Novo Nordisk Pharma Ltd.a grant from Japan Diabetes Foundationa grant from the Smoking Research Foundation to TY
文摘AIM： To explore the mechanism for interactions of leptin with ghrelin and orexin in the arcuate nucleus （ARC） activating neuropeptide Y （NPY） neurons during physiological regulation of feeding, METHODS： Single neurons from ARC of adult rats with matured feeding function were isolated. [Ca2＋]i was measured to monitore their activities. The time course of leptin effects on ghrelin-induced versus orexin-induced [Ca2＋]i increases in NPY neurons was studied. RESULTS： Administration of ghrelin or orexin-A at 101~ mol/L increased cytosolic Ca2~ concentration （[Ca2＋]~） in NPY neurons isolated from the ARC of adult rats. Upon administration of leptin at 10^-14-10^-12 mol/L, ghrelin-induced [Ca2＋]i increases were initially （〈 10 min） inhibited but later restored, exhibiting a transient pattern of inhibition. In contrast, orexin-induced [Ca2＋]i increases were inhibited by leptin in a long- lasting manner. Furthermore, a prior administration of leptin inhibited orexin action but not ghrelin action to increase ICa 2＋li, CONCLUSION： Leptin counteracted ghrelin effects transiently and orexin effects long-lastingly in NPY neurons. The transient property with which leptin counteracts ghrelin action in NPY neurons may allow the fasting-associated increase in ghrelin levels to activate NPY neurons in the presence of physiological leptin and to stimulate feeding.
文摘A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and forms a multifunctional transducing organ that mediates a plethora of cardiovascular processes. The activation of ECs from as state of quiescence is, therefore, regarded among the early events leading to the onset and progression of potentially lethal diseases, such as hypertension, myocardial infarction, brain stroke, and tumor. Intracellular Ca2+ signals have long been know to play a central role in the complex network of signaling pathways regulating the endothelial functions. Notably, recent work has outlined how any change in the pattern of expression of endothelial channels, transporters and pumps involved in the modulation of intracellular Ca2+ levels may dramatically affect whole body homeostasis. Vascular ECs may react to both mechanical and chemical stimuli by generating a variety of intracellular Ca2+ signals, ranging from brief, localized Ca2+ pulses to prolonged Ca2+ oscillations engulfing the whole cytoplasm. The well-defined spatiotemporal profile of the subcellular Ca2+ signals elicited in ECs by specific extracellular inputs depends on the interaction between Ca2+ releasing channels, which arelocated both on the plasma membrane and in a number of intracellular organelles, and Ca2+ removing systems. The present article aims to summarize both the past and recent literature in the field to provide a clear-cut picture of our current knowledge on the molecular nature and the role played by the components of the Ca2+ machinery in vascular ECs under both physiological and pathological conditions.
