AIM To investigate the role of calmodulin-dependent protein kinase Ⅱ(Ca MKⅡ) in colon cancer growth,migration and invasion.METHODS Ca MKⅡ expression in colon cancer and paracancerous tissues was evaluated via immun...AIM To investigate the role of calmodulin-dependent protein kinase Ⅱ(Ca MKⅡ) in colon cancer growth,migration and invasion.METHODS Ca MKⅡ expression in colon cancer and paracancerous tissues was evaluated via immunochemistry. Transcriptional and posttranscriptional levels of Ca MKⅡin tissue samples and MMP2,MMP9 and TIMP-1 expression in the human colon cancer cell line HCT116 were assessed by q RTPCR and western blot. Cell proliferation was detected with the MTT assay. Cancer cell migration and invasion were investigated with the Transwell culture system and woundhealing assay.RESULTS We first demonstrated that CaMK Ⅱ was ove rexpressed in human colon cancers and was associated with cancer differentiation. In the human colon cancer cell line HCT116,the Ca MKII-specific inhibitor KN93,but not its inactive analogue KN92,decreased cancer cell proliferation. Furthermore,KN93 also significantly prohibited HCT116 cell migration and invasion. The specific inhibition of ERK1/2 or p38 decreased the proliferation and migration of colon cancer cells.CONCLUSION Our findings highlight Ca MKⅡ as a potential critical mediator in human colon tumor development and metastasis.展开更多
The adsorption of Ca（ II ） ions from aqueous solution by ehitosan a-ketoglutaric acid （KCTS） and hydroxamated chitosan a-ketoglutaric acid （HKCTS） was studied in a batch adsorption system. The Langmuir and Freun...The adsorption of Ca（ II ） ions from aqueous solution by ehitosan a-ketoglutaric acid （KCTS） and hydroxamated chitosan a-ketoglutaric acid （HKCTS） was studied in a batch adsorption system. The Langmuir and Freundlich adsorption models were applied to describing the equilibrium isotherms, and isotherm constants were determined. The kinetics of the adsorption with respect to the initial Ca（II） ions concentration, temperature and pH was investigated. The pseudo-first-order and second-order kinetic models were used to describe the kinetic data and the rate constants were evaluated. The results show that the experimental data fit well to the Langmuir isotherms with a high correlation coefficient （R2）. The pseudo-second-order rate expression provides the best fitting kinetic model. The pseudo second-order kinetic model is indicated with the activation energy of 26.22 kJ/mol and 6.16 kJ/mol for KCTS and HKCTS, respectively. It is suggested that the overall rate of adsorption of Ca（ II ） ions is likely to be controlled by the chemical process.展开更多
OBJECTIVE To determine the functional role of hydrogen sulfide(H_2S) in protecting against mitochondrial dysfunction in heart failure through the inhibition of Ca^(2+)/calmodulin-dependent protein kinaseⅡ(Ca MKⅡ) us...OBJECTIVE To determine the functional role of hydrogen sulfide(H_2S) in protecting against mitochondrial dysfunction in heart failure through the inhibition of Ca^(2+)/calmodulin-dependent protein kinaseⅡ(Ca MKⅡ) using wild type and CSE knockout mouse models.METHODS Continuous subcutaneous injection isoprenaline(7.5 mg·kg^(-1) per day),once a day for 4 weeks to induce heart failure in male C57BL/6(6-8 weeks old) mice and CSE-/-mice.150 μmol·L^(-1) H_2O_2 was used to induce oxidative stress in H9c2 cells.Echocardiograph was used to detect cardiac parameters.H&E stain and Masson stain was to observation histopathological changes.Western blot was used to detect protein expression and activity.The si RNA was used to silence protein expression.HPLC was used to detect H_2S level.Biotin assay was used to detect the level of S-sulfhydration protein.RESULTS Treatment with S-propyl-L-cysteine(SPRC) or sodium hydrosulfide(Na HS),modulators of blood H_2S levels,attenuated the development of heart failure in animals,reduced lipid peroxidation,and preserved mitochondrial function.The inhibition Ca MKⅡ phosphorylation by SPRC and Na HS as demonstrated using both in vivo and in vitro models corresponded with the cardioprotective effects of these compounds.Interestingly,Ca MKⅡ activity was found to be elevated in CSE-/-mice as compared to wild type animals and the phosphorylation status of Ca MK Ⅱ appeared to relate to the severity of heart failure.Importantly,in wild type mice SPRC was found to promote S-sulfhydration of Ca MKⅡ leading to reduced activity of this protein however,in CSE-/-mice S-sulfhydration was abolished following SPRC treatment.CONCLUSION A novel mechanism depicting a role of S-sulfhydration in the regulation of Ca MKⅡ is presented.SPRC mediated S-sulfhydration of Ca MKⅡ was found to inhibit Ca MKⅡ activity and to preserve cardiovascular homeostasis.展开更多
应用循环伏安法研究Pb Sm Sn和Pb Ca Sn合金电极在4.5mol·dm-3硫酸溶液中和0.6～1.6V(vs.Hg/Hg2SO4)电位范围内的电化学特性,并采用线性电位扫描法和交流伏安法研究了上述合金在相同溶液中分别于0.9和1.28V(vs.Hg/Hg2SO4)生长的阳...应用循环伏安法研究Pb Sm Sn和Pb Ca Sn合金电极在4.5mol·dm-3硫酸溶液中和0.6～1.6V(vs.Hg/Hg2SO4)电位范围内的电化学特性,并采用线性电位扫描法和交流伏安法研究了上述合金在相同溶液中分别于0.9和1.28V(vs.Hg/Hg2SO4)生长的阳极膜的性质.结果表明,Sm代替Pb Ca Sn合金中的Ca在0.9和1.28V电位下均可抑制铅合金阳极膜的生长和降低阳极膜的阻抗,并可减少在高阳极电位(1.6V)时氧气的析出.展开更多
Background Gabapentin has been widely and successfully used in the clinic for many neuropathic pain syndromes since last decade, however its analgesic mechanisms are still elusive. Our study was to investigate whether...Background Gabapentin has been widely and successfully used in the clinic for many neuropathic pain syndromes since last decade, however its analgesic mechanisms are still elusive. Our study was to investigate whether Ca^2＋/calmodulin-dependent protein kinase Ⅱ （CaMKⅡ） contributes to the analgesic effect of gabapentin on a chronic constriction injury （CCI） model. Methods Gabapentin （2%, 100 mg/kg） or saline （0.5 ml/100 g） was injected intraperitoneally 15 minutes prior to surgery and then every 12 hours from postoperative day 0-4 to all rats in control, sham and CCI groups. The analgesic effect of gabapentin was assessed by measuring mechanical allodynia and thermal hyperalgesia of rats. Expression and activation of CaMKⅡ were quantified by reverse-transcriptional polymerase chain reaction and Western blotting. Results The analgesic effect of gabapentin on mechanical allodynia and thermal hyperalgesia was significant in the CCI model, with maximal reduction reached on postoperative day 8. Gabapentin decreased the expression of the total CaMKⅡ and phosphorylated CaMKⅡ in CCI rats. Conclusion The analgesic effect of gabapentin on CCI rats may be related to the decreased expression and phosphorylation of CaMKⅡ in the spinal cord.展开更多
基金Supported by the National Natural Science Foundation of China,No.81302131
文摘AIM To investigate the role of calmodulin-dependent protein kinase Ⅱ(Ca MKⅡ) in colon cancer growth,migration and invasion.METHODS Ca MKⅡ expression in colon cancer and paracancerous tissues was evaluated via immunochemistry. Transcriptional and posttranscriptional levels of Ca MKⅡin tissue samples and MMP2,MMP9 and TIMP-1 expression in the human colon cancer cell line HCT116 were assessed by q RTPCR and western blot. Cell proliferation was detected with the MTT assay. Cancer cell migration and invasion were investigated with the Transwell culture system and woundhealing assay.RESULTS We first demonstrated that CaMK Ⅱ was ove rexpressed in human colon cancers and was associated with cancer differentiation. In the human colon cancer cell line HCT116,the Ca MKII-specific inhibitor KN93,but not its inactive analogue KN92,decreased cancer cell proliferation. Furthermore,KN93 also significantly prohibited HCT116 cell migration and invasion. The specific inhibition of ERK1/2 or p38 decreased the proliferation and migration of colon cancer cells.CONCLUSION Our findings highlight Ca MKⅡ as a potential critical mediator in human colon tumor development and metastasis.
基金Project(20376085) supported by the National Natural Science Foundation of China
文摘The adsorption of Ca（ II ） ions from aqueous solution by ehitosan a-ketoglutaric acid （KCTS） and hydroxamated chitosan a-ketoglutaric acid （HKCTS） was studied in a batch adsorption system. The Langmuir and Freundlich adsorption models were applied to describing the equilibrium isotherms, and isotherm constants were determined. The kinetics of the adsorption with respect to the initial Ca（II） ions concentration, temperature and pH was investigated. The pseudo-first-order and second-order kinetic models were used to describe the kinetic data and the rate constants were evaluated. The results show that the experimental data fit well to the Langmuir isotherms with a high correlation coefficient （R2）. The pseudo-second-order rate expression provides the best fitting kinetic model. The pseudo second-order kinetic model is indicated with the activation energy of 26.22 kJ/mol and 6.16 kJ/mol for KCTS and HKCTS, respectively. It is suggested that the overall rate of adsorption of Ca（ II ） ions is likely to be controlled by the chemical process.
文摘OBJECTIVE To determine the functional role of hydrogen sulfide(H_2S) in protecting against mitochondrial dysfunction in heart failure through the inhibition of Ca^(2+)/calmodulin-dependent protein kinaseⅡ(Ca MKⅡ) using wild type and CSE knockout mouse models.METHODS Continuous subcutaneous injection isoprenaline(7.5 mg·kg^(-1) per day),once a day for 4 weeks to induce heart failure in male C57BL/6(6-8 weeks old) mice and CSE-/-mice.150 μmol·L^(-1) H_2O_2 was used to induce oxidative stress in H9c2 cells.Echocardiograph was used to detect cardiac parameters.H&E stain and Masson stain was to observation histopathological changes.Western blot was used to detect protein expression and activity.The si RNA was used to silence protein expression.HPLC was used to detect H_2S level.Biotin assay was used to detect the level of S-sulfhydration protein.RESULTS Treatment with S-propyl-L-cysteine(SPRC) or sodium hydrosulfide(Na HS),modulators of blood H_2S levels,attenuated the development of heart failure in animals,reduced lipid peroxidation,and preserved mitochondrial function.The inhibition Ca MKⅡ phosphorylation by SPRC and Na HS as demonstrated using both in vivo and in vitro models corresponded with the cardioprotective effects of these compounds.Interestingly,Ca MKⅡ activity was found to be elevated in CSE-/-mice as compared to wild type animals and the phosphorylation status of Ca MK Ⅱ appeared to relate to the severity of heart failure.Importantly,in wild type mice SPRC was found to promote S-sulfhydration of Ca MKⅡ leading to reduced activity of this protein however,in CSE-/-mice S-sulfhydration was abolished following SPRC treatment.CONCLUSION A novel mechanism depicting a role of S-sulfhydration in the regulation of Ca MKⅡ is presented.SPRC mediated S-sulfhydration of Ca MKⅡ was found to inhibit Ca MKⅡ activity and to preserve cardiovascular homeostasis.
文摘应用循环伏安法研究Pb Sm Sn和Pb Ca Sn合金电极在4.5mol·dm-3硫酸溶液中和0.6～1.6V(vs.Hg/Hg2SO4)电位范围内的电化学特性,并采用线性电位扫描法和交流伏安法研究了上述合金在相同溶液中分别于0.9和1.28V(vs.Hg/Hg2SO4)生长的阳极膜的性质.结果表明,Sm代替Pb Ca Sn合金中的Ca在0.9和1.28V电位下均可抑制铅合金阳极膜的生长和降低阳极膜的阻抗,并可减少在高阳极电位(1.6V)时氧气的析出.
基金This research is supported by a grant from the National Natural Science Foundation of China （No. 30672029）.
文摘Background Gabapentin has been widely and successfully used in the clinic for many neuropathic pain syndromes since last decade, however its analgesic mechanisms are still elusive. Our study was to investigate whether Ca^2＋/calmodulin-dependent protein kinase Ⅱ （CaMKⅡ） contributes to the analgesic effect of gabapentin on a chronic constriction injury （CCI） model. Methods Gabapentin （2%, 100 mg/kg） or saline （0.5 ml/100 g） was injected intraperitoneally 15 minutes prior to surgery and then every 12 hours from postoperative day 0-4 to all rats in control, sham and CCI groups. The analgesic effect of gabapentin was assessed by measuring mechanical allodynia and thermal hyperalgesia of rats. Expression and activation of CaMKⅡ were quantified by reverse-transcriptional polymerase chain reaction and Western blotting. Results The analgesic effect of gabapentin on mechanical allodynia and thermal hyperalgesia was significant in the CCI model, with maximal reduction reached on postoperative day 8. Gabapentin decreased the expression of the total CaMKⅡ and phosphorylated CaMKⅡ in CCI rats. Conclusion The analgesic effect of gabapentin on CCI rats may be related to the decreased expression and phosphorylation of CaMKⅡ in the spinal cord.
