The stromal interaction molecule(STIM)-calcium release-activated calcium channel protein(ORAI) and inositol1,4,5-trisphosphate receptors(IP_3Rs) play pivotal roles in the modulation of Ca^(2+)-regulated pathways from ...The stromal interaction molecule(STIM)-calcium release-activated calcium channel protein(ORAI) and inositol1,4,5-trisphosphate receptors(IP_3Rs) play pivotal roles in the modulation of Ca^(2+)-regulated pathways from gene transcription to cell apoptosis by driving calcium-dependent signaling processes.Increasing evidence has implicated the dysregulation of STIM-ORAI and IP_3Rs in tumorigenesis and tumor progression.By controlling the activities,structure,and/or expression levels of these Ca^(2+)-transporting proteins,malignant cancer cells can hijack them to drive essential biological functions for tumor development.However,the molecular mechanisms underlying the participation of STIM-ORAI and IP_3Rs in the biological behavior of cancer remain elusive.In this review,we summarize recent advances regarding STIM-ORAI and IP_3Rs and discuss how they promote cell proliferation,apoptosis evasion,and cell migration through temporal and spatial rearrangements in certain types of malignant cells.An understanding of the essential roles of STIM-ORAI and IP_3Rs may provide new pharmacologic targets that achieve a better therapeutic effect by inhibiting their actions in key intracellular signaling pathways.展开更多
目的:观察通脉愈斑丸治疗2型糖尿病合并颈动脉粥样硬化患者的临床疗效。方法:将符合诊断标准的70例患者按照随机数字表法分为观察组和对照组,每组各35例。对照组在调整生活方式的基础上给予二甲双胍缓释片、阿司匹林肠溶片、阿托伐他汀...目的:观察通脉愈斑丸治疗2型糖尿病合并颈动脉粥样硬化患者的临床疗效。方法:将符合诊断标准的70例患者按照随机数字表法分为观察组和对照组,每组各35例。对照组在调整生活方式的基础上给予二甲双胍缓释片、阿司匹林肠溶片、阿托伐他汀钙片口服,观察组在对照组治疗基础上加服通脉愈斑丸。比较两组患者临床疗效,测量两组患者治疗前后颈动脉内膜中层厚度(intima media thickness,IMT)、斑块面积,检测两组患者治疗前后低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)、空腹血糖(fasting blood glucose,FBG)及糖化血红蛋白(glycosylated hemoglobin,HbA1c)水平。结果:观察组有效率为97.06%,对照组有效率为84.85%,两组有效率比较,差异具有统计学意义(P<0.05)。两组患者治疗后IMT与斑块面积均小于本组治疗前,且观察组治疗后小于对照组治疗后,差异有统计学意义(P<0.05)。两组患者治疗后LDL-c、FBG、HBA1c水平均低于本组治疗前,且观察组治疗后低于对照组治疗后,差异有统计学意义(P<0.05)。结论:通脉愈斑丸治疗2型糖尿病合并颈动脉粥样硬化,可降低患者血糖水平及颈动脉IMT,缩小斑块面积。展开更多
Using fura-2-acetoxymethyl ester (AM) fluorescence imaging and patch clamp techniques, we found that endothelin-1 (ET-1) significantly elevated the intracellular calcium level ([Ca2+]i) in a dose-dependent manner and ...Using fura-2-acetoxymethyl ester (AM) fluorescence imaging and patch clamp techniques, we found that endothelin-1 (ET-1) significantly elevated the intracellular calcium level ([Ca2+]i) in a dose-dependent manner and activated the L-type Ca2+ channel in cardiomyocytes isolated from rats. The effect of ET-1 on [Ca2+]i elevation was abolished in the presence of the ETA receptor blocker BQ123, but was not affected by the ETB receptor blocker BQ788. ET-1-induced an increase in [Ca2+]i, which was inhibited 46.7% by pretreatment with a high concentration of ryanodine (10 μmol/L), a blocker of the ryanodine receptor. The ET-1-induced [Ca2+]i increase was also inhibited by the inhibitors of protein kinase A (PKA), protein kinase C (PKC) and angiotensin type 1 receptor (AT1 receptor). We found that ET-1 induced an enhancement of the amplitude of the whole cell L-type Ca2+ channel current and an increase of open-state probability (NPo) of an L-type single Ca2+ channel. BQ123 completely blocked the ET-1-induced increase in calcium channel open-state probability. In this study we demonstrated that ET-1 regulates calcium overload through a series of mechanisms that include L-type Ca2+ channel activation and Ca2+-induced Ca2+ release (CICR). ETA receptors, PKC, PKA and AT1 receptors may also contribute to this pathway.展开更多
文摘The stromal interaction molecule(STIM)-calcium release-activated calcium channel protein(ORAI) and inositol1,4,5-trisphosphate receptors(IP_3Rs) play pivotal roles in the modulation of Ca^(2+)-regulated pathways from gene transcription to cell apoptosis by driving calcium-dependent signaling processes.Increasing evidence has implicated the dysregulation of STIM-ORAI and IP_3Rs in tumorigenesis and tumor progression.By controlling the activities,structure,and/or expression levels of these Ca^(2+)-transporting proteins,malignant cancer cells can hijack them to drive essential biological functions for tumor development.However,the molecular mechanisms underlying the participation of STIM-ORAI and IP_3Rs in the biological behavior of cancer remain elusive.In this review,we summarize recent advances regarding STIM-ORAI and IP_3Rs and discuss how they promote cell proliferation,apoptosis evasion,and cell migration through temporal and spatial rearrangements in certain types of malignant cells.An understanding of the essential roles of STIM-ORAI and IP_3Rs may provide new pharmacologic targets that achieve a better therapeutic effect by inhibiting their actions in key intracellular signaling pathways.
文摘目的:观察通脉愈斑丸治疗2型糖尿病合并颈动脉粥样硬化患者的临床疗效。方法:将符合诊断标准的70例患者按照随机数字表法分为观察组和对照组,每组各35例。对照组在调整生活方式的基础上给予二甲双胍缓释片、阿司匹林肠溶片、阿托伐他汀钙片口服,观察组在对照组治疗基础上加服通脉愈斑丸。比较两组患者临床疗效,测量两组患者治疗前后颈动脉内膜中层厚度(intima media thickness,IMT)、斑块面积,检测两组患者治疗前后低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)、空腹血糖(fasting blood glucose,FBG)及糖化血红蛋白(glycosylated hemoglobin,HbA1c)水平。结果:观察组有效率为97.06%,对照组有效率为84.85%,两组有效率比较,差异具有统计学意义(P<0.05)。两组患者治疗后IMT与斑块面积均小于本组治疗前,且观察组治疗后小于对照组治疗后,差异有统计学意义(P<0.05)。两组患者治疗后LDL-c、FBG、HBA1c水平均低于本组治疗前,且观察组治疗后低于对照组治疗后,差异有统计学意义(P<0.05)。结论:通脉愈斑丸治疗2型糖尿病合并颈动脉粥样硬化,可降低患者血糖水平及颈动脉IMT,缩小斑块面积。
基金Supported by the National Natural Science Foundation of China (Grant No. 200830870910).
文摘Using fura-2-acetoxymethyl ester (AM) fluorescence imaging and patch clamp techniques, we found that endothelin-1 (ET-1) significantly elevated the intracellular calcium level ([Ca2+]i) in a dose-dependent manner and activated the L-type Ca2+ channel in cardiomyocytes isolated from rats. The effect of ET-1 on [Ca2+]i elevation was abolished in the presence of the ETA receptor blocker BQ123, but was not affected by the ETB receptor blocker BQ788. ET-1-induced an increase in [Ca2+]i, which was inhibited 46.7% by pretreatment with a high concentration of ryanodine (10 μmol/L), a blocker of the ryanodine receptor. The ET-1-induced [Ca2+]i increase was also inhibited by the inhibitors of protein kinase A (PKA), protein kinase C (PKC) and angiotensin type 1 receptor (AT1 receptor). We found that ET-1 induced an enhancement of the amplitude of the whole cell L-type Ca2+ channel current and an increase of open-state probability (NPo) of an L-type single Ca2+ channel. BQ123 completely blocked the ET-1-induced increase in calcium channel open-state probability. In this study we demonstrated that ET-1 regulates calcium overload through a series of mechanisms that include L-type Ca2+ channel activation and Ca2+-induced Ca2+ release (CICR). ETA receptors, PKC, PKA and AT1 receptors may also contribute to this pathway.
