The present work primarily aims to explore the neuronal calcium(Ca^(2+)),IP_(3),and dopamine(DA)signaling systems through a feedback loop model.To date,there has been no exploration of this feedback model in fractiona...The present work primarily aims to explore the neuronal calcium(Ca^(2+)),IP_(3),and dopamine(DA)signaling systems through a feedback loop model.To date,there has been no exploration of this feedback model in fractional-order dynamical systems.This feedback loop model incorporates several crucial mechanisms like the buffering process,IP_(3)-receptor,ryanodine receptor,plasma membrane Ca^(2+)ATPase and sarcoplasmic/endoplasmic reticulum calcium ATPase(SERCA)pump,leak,sodium-calcium exchanger,voltage-gated Ca^(2+)channel,Orai channels,DA-dependent IP_(3)synthesis,and others.By incorporating these mechanisms,the model aims to provide a more comprehensive and realistic understanding of the system under investigation.The present model incorporates fractional-order dynamics along both spatial and temporal dimensions to examine the impacts of superdiffusion and memory showing Brownian motion of Ca^(2+),IP_(3),and DA signaling molecules.The bidirectional feedback between calcium and IP_(3)signaling systems,unidirectional feedback between calcium and dopamine signaling systems,and unidirectional feedback between IP_(3)and dopamine signaling systems have been incorporated into the present model.These feedback loops establish interactions among calcium,IP_(3),and dopamine signaling systems within neuronal cells.The numerical findings were obtained by using the Crank-Nicholson method with the Grunwald technique for fractional space derivatives and the L1method for fractional time derivatives in conjunction with the Gauss-Seidel Iterations.This research specifically investigates the implications of cell memory as well as superdiffusion on Ca^(2+),IP_(3),and DA dynamics in neuronal cells,which are interactive nonlinear systems.The superdiffusion process results in a reduction in Ca^(2+),IP_(3),and DA concentrations,while cellular memory leads to an increase in ion and molecule concentrations in neuronal cells during the initial time.The disruption of any given process can lead to imbalances in calcium,IP_(3),and DA systems,hence contributing to neurotoxicity and cellular demise.展开更多
In our previous reports, wehave verified the involvement of G protein, Ca2+ channel in plasma memband CDPK in extracellular calmodulin(CaM) signal transduction chain for theinitiatory effects of extracellular CaM onpo...In our previous reports, wehave verified the involvement of G protein, Ca2+ channel in plasma memband CDPK in extracellular calmodulin(CaM) signal transduction chain for theinitiatory effects of extracellular CaM onpollen germination and pollen tubegrowth . In this paper, both normal andexogenous CaM-enhanced pollen germination and tube growth were completelyinhibited by the phospholipase C inhibitor U-73122 (Fig. 1 ). The enhancement of pollen germination and tubegrowth by the G protein agonist choleratoxin were also completely inhibited byU-73122 (Fig. 2), whereas the inhibition of pollen germination and tubegrowth by the G protein antagonist pertussis toxin was reversed by IP3 (Fig. 2).Heparin, an antagonist Of IP3 receptor,inhibited pollen germination and tubegrowth (Fig. 3 ), while thapsigargin increased cytosolic Ca2+ by inhibiting theIP3-specific Ca2+ pump in endoplasmicreticulum, and thereby increased pollengermination and tube growth (Fig. 4).The above results suggest that phosphoinositide signaling pathway might be involved in the extracellular CaM signaltransduction chain in the initiatory effectsof extracellular CaM on pollen germination and tube growth.展开更多
AIM:To explore the effect and mechanism of gastrin and its antagonists prog lumide and somatostatin on colorectal carcinoma and their clinical significance.METHODS:A model of transplanted human colonic carcinoma was e...AIM:To explore the effect and mechanism of gastrin and its antagonists prog lumide and somatostatin on colorectal carcinoma and their clinical significance.METHODS:A model of transplanted human colonic carcinoma was established from SW480 cell line in gymnomouse body.The volume and weight of transplanted carcinoma was observed under the effect of pentagatrin (PG), proglumide (PGL) and octapeptide somotostatin (SMS201-995, SMS). The cAMP content of carcinoma cell was determined by radioimmunoassay and the DNA, protein content and cell cycle were determined by flow-cytometry. The amount of viable cells was determined by MTT colorimetric analysis,IP(3) content was determined by radioimmunoassay, Ca(2+) concentration in cell by fluorometry and PKC activity by isotopic enzymolysis. The expression of gastrin, c-myc, c-fos and rasP21 in 48 cases of colorectal carcinoma tissue was detected by the immuno-cytochemistry SP method. Argyrophilia nucleolar organizer regions was determined with argyrophilia stain.RESULTS:The volume,weight, cAMP, DNA and protein content in carcinoma cell, cell amount and proliferation index of S and G(2)M phase in PG group were all significantly higher than those of control group. When PG was at the concentration of 25mg/L, the amount of viable cells, IP(3) content and Ca(2+) concentration in cell and membrane PKC activity in PG group were significantly higher than those in control group; when PGL was at a concentration of 32mg/L, they dropped to the lowest level in PG (25mg/L)+PGL group, but without significant difference from the control group. The positive expression rate of gastrin, c-myc, c-fos and rasP21 in carcinoma tissue was 39.6%, 54.2%, 47.9% and 54.2% respectively and significantly higher than that in mucosa 3cm and 6cm adjacent to carcinoma tissue and normal colorectal mucosa. The positive expression rate of gastrin of highly differentiated adenocarcinoma group was significantly higher than that of poorly differentiated and mucinous adenocar-cinoma groups. The AgNORs count of carcinoma tissue was significantly higher than that in mucosa 3cm and 6cm adjacent to carcinoma tissue and normal colorectal mucosa; and the positive expression of c-myc and c-fos and the AgNORs count in gastrin-positive group was significantly higher than those in gastrin negative group.CONCLUSION:Pentagastrin has a promoting effect on the growth of transplanted human colonic carcinoma from SW480 cell line. PGL has no obvious effect on the growth of human colonic carcinoma SW480 cell line, but could inhibit the growth promoting effect of PG on transplanted carcinoma. Somatostatin can not only inhibit the growth of transplanted human colonic carcinoma from SW480 cell line directly but also depress the growth-promoting effect of gastrin on the transplanted carcinoma. Some colorectal carcinoma cells can produce and secrete gastrin through autocrine, highly differentiated adenocarcinoma express the highest level gastrin.Endogenous gastrin can stimulate the cell division and proliferation of carcinoma cell and promote the growth of colorectal carcinoma regulating the expression of oncogene c-myc, c-fos. Our study has provided experimental basis for the adjuvant treatment using gastrin antagonist such as PGL, somatostatin of patients with colorectal carcinoma.展开更多
Inositol 1,4,5-trisphosphate 3-kinase(IP33-kinase/IP3K)plays an important role in signal transduction in animal cellsby phosphorylating inositol 1,4,5-trisphosphate(IP3)to inositol 1,3,4,5-tetrakisphosphate(IP4).Both ...Inositol 1,4,5-trisphosphate 3-kinase(IP33-kinase/IP3K)plays an important role in signal transduction in animal cellsby phosphorylating inositol 1,4,5-trisphosphate(IP3)to inositol 1,3,4,5-tetrakisphosphate(IP4).Both IP3 and IP4 arecritical second messengers which regulate calcium(Ca2+)homeostasis.Mammalian IP3Ks are involved in many biologicalprocesses,including brain development,memory,learning and so on.It is widely reported that Ca2+is a canonicalsecond messenger in higher plants.Therefore,plant IP3K should also play a crucial role in plant development.Recently,we reported the identification of plant IP3K gene(AtIpk2β/AtIP3K)from Arabidopsis thaliana and its characterization.Here,we summarize the molecular cloning,biochemical properties and biological functions of IP3Ks from animal,yeastand plant.This review also discusses potential functions of IP3Ks in signaling crosstalk,inositol phosphate metabolism,gene transcriptional control and so on.展开更多
文摘The present work primarily aims to explore the neuronal calcium(Ca^(2+)),IP_(3),and dopamine(DA)signaling systems through a feedback loop model.To date,there has been no exploration of this feedback model in fractional-order dynamical systems.This feedback loop model incorporates several crucial mechanisms like the buffering process,IP_(3)-receptor,ryanodine receptor,plasma membrane Ca^(2+)ATPase and sarcoplasmic/endoplasmic reticulum calcium ATPase(SERCA)pump,leak,sodium-calcium exchanger,voltage-gated Ca^(2+)channel,Orai channels,DA-dependent IP_(3)synthesis,and others.By incorporating these mechanisms,the model aims to provide a more comprehensive and realistic understanding of the system under investigation.The present model incorporates fractional-order dynamics along both spatial and temporal dimensions to examine the impacts of superdiffusion and memory showing Brownian motion of Ca^(2+),IP_(3),and DA signaling molecules.The bidirectional feedback between calcium and IP_(3)signaling systems,unidirectional feedback between calcium and dopamine signaling systems,and unidirectional feedback between IP_(3)and dopamine signaling systems have been incorporated into the present model.These feedback loops establish interactions among calcium,IP_(3),and dopamine signaling systems within neuronal cells.The numerical findings were obtained by using the Crank-Nicholson method with the Grunwald technique for fractional space derivatives and the L1method for fractional time derivatives in conjunction with the Gauss-Seidel Iterations.This research specifically investigates the implications of cell memory as well as superdiffusion on Ca^(2+),IP_(3),and DA dynamics in neuronal cells,which are interactive nonlinear systems.The superdiffusion process results in a reduction in Ca^(2+),IP_(3),and DA concentrations,while cellular memory leads to an increase in ion and molecule concentrations in neuronal cells during the initial time.The disruption of any given process can lead to imbalances in calcium,IP_(3),and DA systems,hence contributing to neurotoxicity and cellular demise.
文摘In our previous reports, wehave verified the involvement of G protein, Ca2+ channel in plasma memband CDPK in extracellular calmodulin(CaM) signal transduction chain for theinitiatory effects of extracellular CaM onpollen germination and pollen tubegrowth . In this paper, both normal andexogenous CaM-enhanced pollen germination and tube growth were completelyinhibited by the phospholipase C inhibitor U-73122 (Fig. 1 ). The enhancement of pollen germination and tubegrowth by the G protein agonist choleratoxin were also completely inhibited byU-73122 (Fig. 2), whereas the inhibition of pollen germination and tubegrowth by the G protein antagonist pertussis toxin was reversed by IP3 (Fig. 2).Heparin, an antagonist Of IP3 receptor,inhibited pollen germination and tubegrowth (Fig. 3 ), while thapsigargin increased cytosolic Ca2+ by inhibiting theIP3-specific Ca2+ pump in endoplasmicreticulum, and thereby increased pollengermination and tube growth (Fig. 4).The above results suggest that phosphoinositide signaling pathway might be involved in the extracellular CaM signaltransduction chain in the initiatory effectsof extracellular CaM on pollen germination and tube growth.
文摘AIM:To explore the effect and mechanism of gastrin and its antagonists prog lumide and somatostatin on colorectal carcinoma and their clinical significance.METHODS:A model of transplanted human colonic carcinoma was established from SW480 cell line in gymnomouse body.The volume and weight of transplanted carcinoma was observed under the effect of pentagatrin (PG), proglumide (PGL) and octapeptide somotostatin (SMS201-995, SMS). The cAMP content of carcinoma cell was determined by radioimmunoassay and the DNA, protein content and cell cycle were determined by flow-cytometry. The amount of viable cells was determined by MTT colorimetric analysis,IP(3) content was determined by radioimmunoassay, Ca(2+) concentration in cell by fluorometry and PKC activity by isotopic enzymolysis. The expression of gastrin, c-myc, c-fos and rasP21 in 48 cases of colorectal carcinoma tissue was detected by the immuno-cytochemistry SP method. Argyrophilia nucleolar organizer regions was determined with argyrophilia stain.RESULTS:The volume,weight, cAMP, DNA and protein content in carcinoma cell, cell amount and proliferation index of S and G(2)M phase in PG group were all significantly higher than those of control group. When PG was at the concentration of 25mg/L, the amount of viable cells, IP(3) content and Ca(2+) concentration in cell and membrane PKC activity in PG group were significantly higher than those in control group; when PGL was at a concentration of 32mg/L, they dropped to the lowest level in PG (25mg/L)+PGL group, but without significant difference from the control group. The positive expression rate of gastrin, c-myc, c-fos and rasP21 in carcinoma tissue was 39.6%, 54.2%, 47.9% and 54.2% respectively and significantly higher than that in mucosa 3cm and 6cm adjacent to carcinoma tissue and normal colorectal mucosa. The positive expression rate of gastrin of highly differentiated adenocarcinoma group was significantly higher than that of poorly differentiated and mucinous adenocar-cinoma groups. The AgNORs count of carcinoma tissue was significantly higher than that in mucosa 3cm and 6cm adjacent to carcinoma tissue and normal colorectal mucosa; and the positive expression of c-myc and c-fos and the AgNORs count in gastrin-positive group was significantly higher than those in gastrin negative group.CONCLUSION:Pentagastrin has a promoting effect on the growth of transplanted human colonic carcinoma from SW480 cell line. PGL has no obvious effect on the growth of human colonic carcinoma SW480 cell line, but could inhibit the growth promoting effect of PG on transplanted carcinoma. Somatostatin can not only inhibit the growth of transplanted human colonic carcinoma from SW480 cell line directly but also depress the growth-promoting effect of gastrin on the transplanted carcinoma. Some colorectal carcinoma cells can produce and secrete gastrin through autocrine, highly differentiated adenocarcinoma express the highest level gastrin.Endogenous gastrin can stimulate the cell division and proliferation of carcinoma cell and promote the growth of colorectal carcinoma regulating the expression of oncogene c-myc, c-fos. Our study has provided experimental basis for the adjuvant treatment using gastrin antagonist such as PGL, somatostatin of patients with colorectal carcinoma.
基金supported by grants from the National Natural Science Foundation of China(No.30370142)the National Special Key Project on Functional Genomics and Biochip of China(No.2002AA2Z1002)the Project sponsored by the Scientific Research Foundation for the Returned Oversea Chinese Scholars,State Education Ministry.
文摘Inositol 1,4,5-trisphosphate 3-kinase(IP33-kinase/IP3K)plays an important role in signal transduction in animal cellsby phosphorylating inositol 1,4,5-trisphosphate(IP3)to inositol 1,3,4,5-tetrakisphosphate(IP4).Both IP3 and IP4 arecritical second messengers which regulate calcium(Ca2+)homeostasis.Mammalian IP3Ks are involved in many biologicalprocesses,including brain development,memory,learning and so on.It is widely reported that Ca2+is a canonicalsecond messenger in higher plants.Therefore,plant IP3K should also play a crucial role in plant development.Recently,we reported the identification of plant IP3K gene(AtIpk2β/AtIP3K)from Arabidopsis thaliana and its characterization.Here,we summarize the molecular cloning,biochemical properties and biological functions of IP3Ks from animal,yeastand plant.This review also discusses potential functions of IP3Ks in signaling crosstalk,inositol phosphate metabolism,gene transcriptional control and so on.
