Cytosolic Ca^2＋ is an important second messenger in virtually every type of cell. Moreover, Ca^2＋ generally regulates multiple activities within individual cells. This article reviews the cellular machinery that is ...Cytosolic Ca^2＋ is an important second messenger in virtually every type of cell. Moreover, Ca^2＋ generally regulates multiple activities within individual cells. This article reviews the cellular machinery that is responsible for Ca^2＋ signaling in cholangiocytes. In addition, two Ca^2＋-mediated events in cholangiocytes are discussed： bicarbonate secretion and apoptosis. Finally, emerging evidence is reviewed that Ca^2＋ signaling is involved in the pathogenesis of diseases affecting the biliary tree and that Ca^2＋ signaling pathways can be manipulated to therapeutic advantage in the treatment of cholestatic disorders.展开更多
AIM: To investigate the effects of anti-fibrosis I herbal compound on intracellular Ca2+ in activated hepatic stellate cell (HSC) and to try to survey its molecular mechanism in treatment and prevention of hepatic fib...AIM: To investigate the effects of anti-fibrosis I herbal compound on intracellular Ca2+ in activated hepatic stellate cell (HSC) and to try to survey its molecular mechanism in treatment and prevention of hepatic fibrosis and portal hypertension. METHODS: The activated HSC line was plated on small glass cover slips in 24 wells culture dishes at a density of 5×106 /mL, and incubated in RPMI-1640 media for 24 h. After the cells were loaded with Fluo-3/AM, intracellular Ca2+ was measured with laser scanning confocal microscopy (LSCM). The dynamic changes of intracellular Ca2+, stimulated by carbon tetrachloride, TGF-β1 antibody and the drug serum of anti-fibrosis I herbal compound and under orthogonal design were determined by LSCM. The effect of anti-fibrosis I herbal compound on intracellular Ca2+ was observed before and after the addition of TGF-β1 antibody. RESULTS: The intracellular Ca2+ were significantly different in different dosage of carbon tetrachloride anti-fibrosis I formula drug serum, TGF-β1 antibody and different turn of these substance, but their interval time between CCl4 and TGF-β1 antibody, CCl4 and anti-fibrosis I drug serum had no influence on intracellular Ca2+. The result showed intracellular Ca2+ wasn't significantly different between rat serum without anti-fibrosis I and untreated group. After carbon tetrachloride stimulation, intracellular Ca2+ of activated HSC increased significantly when the dosage of CCl4 from 5 to 15 mmol/L, however, decreased significantly after stimulation by 5-20 μg/mL TGF-β1 antibody or 5-20 mL/L drug serum. Moreover, before and after the addition of TGF-β1 antibody, intracellular Ca2+ was significantly different. These results suggested that the molecular mechanism was independent of blocking TGF-β1 effects. CONCLUSION: Anti-fibrosis I herbal compound may treat hepatic fibrosis and decrease portal hypertension by inhibiting activated HSC contractility through decrease of intracellular Ca2+.展开更多
The activation of Ca2+ entry through store-operated channels by agonists that deplete Ca2+ from the endoplasmic reticulum (ER) is a ubiquitous signaling mechanism, the molecular basis of which has remained elusive for...The activation of Ca2+ entry through store-operated channels by agonists that deplete Ca2+ from the endoplasmic reticulum (ER) is a ubiquitous signaling mechanism, the molecular basis of which has remained elusive for the past two decades. Store-operated Ca2+-release-activated Ca2+ (CRAC) channels constitute the sole pathway for Ca2+ entry following antigen-receptor engagement. In a set of breakthrough studies over the past two years, stromal interaction molecule 1 (STIM1, the ER Ca2+ sensor) and Orai1 (a pore-forming subunit of the CRAC channel) have been identified. Here we review these recent studies and the insights they provide into the mechanism of store-operated Ca2+ channels (SOCCs).展开更多
To study the role of Ca2+ in the pathogenesis of pituitary growth hormone secreting adenomas, the function of Ca2+ in 23 cases of human Prturtary GH-secreting adenoma was investigated in monolayer cell culture. It wa...To study the role of Ca2+ in the pathogenesis of pituitary growth hormone secreting adenomas, the function of Ca2+ in 23 cases of human Prturtary GH-secreting adenoma was investigated in monolayer cell culture. It was found that Ca2+ channel blockers nicardipin and nifedipin inhibrted basal and growth hormone releasing hormone (GRH)stimulated GH secretion in 87. 5 % and 100. 0 % of the GH adenomas . respectively, demonstrating that in most human pituitary GH adenomas, the basal and GRH regulated GH secretion is Ca2+ dependent. The GRH and sometostatin (SRIF) agonist octreotide regulated the processes of GH secretion via Ca2+ had defects in different steps including receptor ,postreceptor Ca2+ channel and Ca2+GH secreting coupling in 6 (66. 6%) and 5 (55. 5 % ) cases of 9 GH adenomas respectively. Among them,the defects in GRH receptor and SRIF regulated Ca2+ channel are the main causes of the dysfunction of GH adenomas. These defects may be related to GH hypersecretion in GH adenomas. Our data provides advance evidences for intrinsic defects of GH adenomas.展开更多
This study focused on the influences of opioids on the generation of antibody against sheep erythrocyte in vitro, It was found that morphine. a-CAO, DADLE, MENK were able to inhibit the capacity of murine spleen cell...This study focused on the influences of opioids on the generation of antibody against sheep erythrocyte in vitro, It was found that morphine. a-CAO, DADLE, MENK were able to inhibit the capacity of murine spleen cells to generate antibody and leukotriene C4 and conversely. dynorphin was able to stimulate the capacity of murine spleen cells to generate antibody and leukotriene C4. Morphine, a-CAO, MENK, DADLE, dynorphin decreased intracellular cAMP level, increased [Ca(2+)]i and calmodulin activity. The effects were completely blocked by naloxone, the specific opioid antagonist. Our results showed that opioids regulate the production of antibody in murine spleen cells, and alter intracellular cAMP, [Ca(2+)]i calmodulin activity. and leukotriene C4 production by way of binding to different receptor types.展开更多
Intracellular Ca2+ is vital for cell physiology.Disruption of Ca2+ homeostasis contributes to human diseases such as heart failure,neuron-degeneration,and diabetes.To ensure an effective intracellular Ca2+ dynamics,va...Intracellular Ca2+ is vital for cell physiology.Disruption of Ca2+ homeostasis contributes to human diseases such as heart failure,neuron-degeneration,and diabetes.To ensure an effective intracellular Ca2+ dynamics,various Ca2+ transport proteins localized in different cellular regions have to work in coordination.The central role of mitochondrial Ca2+ transport mechanisms in responding to physiological Ca2+ pulses in cytosol is to take up Ca2+ for regulating energy production and shaping the amplitude and duration of Ca2+ transients in various micro-domains.Since the discovery that isolated mitochondria can take up large quantities of Ca2+ approximately 5 decades ago,extensive studies have been focused on the functional characterization and implication of ion channels that dictate Ca2+ transport across the inner mitochondrial membrane.The mitochondrial Ca2+ uptake sensitive to non-specific inhibitors ruthenium red and Ru360 has long been considered as the activity of mitochondrial Ca2+ uniporter(MCU) .The general consensus is that MCU is dominantly or exclusively responsible for the mitochondrial Ca2+ influx.Since multiple Ca2+ influx mechanisms(e.g.L-,T-,and N-type Ca2+ channel) have their unique functions in the plasma membrane,it is plausible that mitochondrial inner membrane has more than just MCU to decode complex intracellular Ca2+ signaling in various cell types.During the last decade,four molecular identities related to mitochondrial Ca2+ influx mechanisms have been identified.These are mitochondrial ryanodine receptor,mitochondrial uncoupling proteins,LETM1(Ca2+ /H+ exchanger) ,and MCU and its Ca2+ sensing regulatory subunit MICU1.Here,we briefly review recent progress in these and other reported mitochondrial Ca2+ influx pathways and their differences in kinetics,Ca2+ dependence,and pharmacological characteristics.Their potential physiological and pathological implications are also discussed.展开更多
基金NIH grants DK61747, DK45710, DK57751, and DK34989, and by a grant-in-aid from the American Heart Association
文摘Cytosolic Ca^2＋ is an important second messenger in virtually every type of cell. Moreover, Ca^2＋ generally regulates multiple activities within individual cells. This article reviews the cellular machinery that is responsible for Ca^2＋ signaling in cholangiocytes. In addition, two Ca^2＋-mediated events in cholangiocytes are discussed： bicarbonate secretion and apoptosis. Finally, emerging evidence is reviewed that Ca^2＋ signaling is involved in the pathogenesis of diseases affecting the biliary tree and that Ca^2＋ signaling pathways can be manipulated to therapeutic advantage in the treatment of cholestatic disorders.
基金Supported by the National Science Foundation of Hebei Province,No. 302489
文摘AIM: To investigate the effects of anti-fibrosis I herbal compound on intracellular Ca2+ in activated hepatic stellate cell (HSC) and to try to survey its molecular mechanism in treatment and prevention of hepatic fibrosis and portal hypertension. METHODS: The activated HSC line was plated on small glass cover slips in 24 wells culture dishes at a density of 5×106 /mL, and incubated in RPMI-1640 media for 24 h. After the cells were loaded with Fluo-3/AM, intracellular Ca2+ was measured with laser scanning confocal microscopy (LSCM). The dynamic changes of intracellular Ca2+, stimulated by carbon tetrachloride, TGF-β1 antibody and the drug serum of anti-fibrosis I herbal compound and under orthogonal design were determined by LSCM. The effect of anti-fibrosis I herbal compound on intracellular Ca2+ was observed before and after the addition of TGF-β1 antibody. RESULTS: The intracellular Ca2+ were significantly different in different dosage of carbon tetrachloride anti-fibrosis I formula drug serum, TGF-β1 antibody and different turn of these substance, but their interval time between CCl4 and TGF-β1 antibody, CCl4 and anti-fibrosis I drug serum had no influence on intracellular Ca2+. The result showed intracellular Ca2+ wasn't significantly different between rat serum without anti-fibrosis I and untreated group. After carbon tetrachloride stimulation, intracellular Ca2+ of activated HSC increased significantly when the dosage of CCl4 from 5 to 15 mmol/L, however, decreased significantly after stimulation by 5-20 μg/mL TGF-β1 antibody or 5-20 mL/L drug serum. Moreover, before and after the addition of TGF-β1 antibody, intracellular Ca2+ was significantly different. These results suggested that the molecular mechanism was independent of blocking TGF-β1 effects. CONCLUSION: Anti-fibrosis I herbal compound may treat hepatic fibrosis and decrease portal hypertension by inhibiting activated HSC contractility through decrease of intracellular Ca2+.
文摘The activation of Ca2+ entry through store-operated channels by agonists that deplete Ca2+ from the endoplasmic reticulum (ER) is a ubiquitous signaling mechanism, the molecular basis of which has remained elusive for the past two decades. Store-operated Ca2+-release-activated Ca2+ (CRAC) channels constitute the sole pathway for Ca2+ entry following antigen-receptor engagement. In a set of breakthrough studies over the past two years, stromal interaction molecule 1 (STIM1, the ER Ca2+ sensor) and Orai1 (a pore-forming subunit of the CRAC channel) have been identified. Here we review these recent studies and the insights they provide into the mechanism of store-operated Ca2+ channels (SOCCs).
文摘To study the role of Ca2+ in the pathogenesis of pituitary growth hormone secreting adenomas, the function of Ca2+ in 23 cases of human Prturtary GH-secreting adenoma was investigated in monolayer cell culture. It was found that Ca2+ channel blockers nicardipin and nifedipin inhibrted basal and growth hormone releasing hormone (GRH)stimulated GH secretion in 87. 5 % and 100. 0 % of the GH adenomas . respectively, demonstrating that in most human pituitary GH adenomas, the basal and GRH regulated GH secretion is Ca2+ dependent. The GRH and sometostatin (SRIF) agonist octreotide regulated the processes of GH secretion via Ca2+ had defects in different steps including receptor ,postreceptor Ca2+ channel and Ca2+GH secreting coupling in 6 (66. 6%) and 5 (55. 5 % ) cases of 9 GH adenomas respectively. Among them,the defects in GRH receptor and SRIF regulated Ca2+ channel are the main causes of the dysfunction of GH adenomas. These defects may be related to GH hypersecretion in GH adenomas. Our data provides advance evidences for intrinsic defects of GH adenomas.
文摘This study focused on the influences of opioids on the generation of antibody against sheep erythrocyte in vitro, It was found that morphine. a-CAO, DADLE, MENK were able to inhibit the capacity of murine spleen cells to generate antibody and leukotriene C4 and conversely. dynorphin was able to stimulate the capacity of murine spleen cells to generate antibody and leukotriene C4. Morphine, a-CAO, MENK, DADLE, dynorphin decreased intracellular cAMP level, increased [Ca(2+)]i and calmodulin activity. The effects were completely blocked by naloxone, the specific opioid antagonist. Our results showed that opioids regulate the production of antibody in murine spleen cells, and alter intracellular cAMP, [Ca(2+)]i calmodulin activity. and leukotriene C4 production by way of binding to different receptor types.
基金supported by NIH grants(Grant Nos.HL-033333 and HL093671)to Shey-Shing Sheu
文摘Intracellular Ca2+ is vital for cell physiology.Disruption of Ca2+ homeostasis contributes to human diseases such as heart failure,neuron-degeneration,and diabetes.To ensure an effective intracellular Ca2+ dynamics,various Ca2+ transport proteins localized in different cellular regions have to work in coordination.The central role of mitochondrial Ca2+ transport mechanisms in responding to physiological Ca2+ pulses in cytosol is to take up Ca2+ for regulating energy production and shaping the amplitude and duration of Ca2+ transients in various micro-domains.Since the discovery that isolated mitochondria can take up large quantities of Ca2+ approximately 5 decades ago,extensive studies have been focused on the functional characterization and implication of ion channels that dictate Ca2+ transport across the inner mitochondrial membrane.The mitochondrial Ca2+ uptake sensitive to non-specific inhibitors ruthenium red and Ru360 has long been considered as the activity of mitochondrial Ca2+ uniporter(MCU) .The general consensus is that MCU is dominantly or exclusively responsible for the mitochondrial Ca2+ influx.Since multiple Ca2+ influx mechanisms(e.g.L-,T-,and N-type Ca2+ channel) have their unique functions in the plasma membrane,it is plausible that mitochondrial inner membrane has more than just MCU to decode complex intracellular Ca2+ signaling in various cell types.During the last decade,four molecular identities related to mitochondrial Ca2+ influx mechanisms have been identified.These are mitochondrial ryanodine receptor,mitochondrial uncoupling proteins,LETM1(Ca2+ /H+ exchanger) ,and MCU and its Ca2+ sensing regulatory subunit MICU1.Here,we briefly review recent progress in these and other reported mitochondrial Ca2+ influx pathways and their differences in kinetics,Ca2+ dependence,and pharmacological characteristics.Their potential physiological and pathological implications are also discussed.
