Recent studies have demonstrated that Notch-1 expression is increased in the hippocampus of Alzheimer＇s disease patients. We speculate that Notch-1 signaling may be involved in PC12 cell apoptosis induced by amyloid ...Recent studies have demonstrated that Notch-1 expression is increased in the hippocampus of Alzheimer＇s disease patients. We speculate that Notch-1 signaling may be involved in PC12 cell apoptosis induced by amyloid beta-peptide （25-35） （Aβ25-35）. In the present study, PC12 cells were cultured with different doses （0, 0.1, 1.0, 10 and 100 nmol/L） of N-[N-（3,5-Difluorophenacetyl）-L-alanyl]-S-phenylglycine t-butyl ester, a Notch-1 signaling pathway inhibitor, for 30 minutes. Then cultured cells were induced with Aβ25-3s for 48 hours. Pretreatment of PC12 cells with high doses of N-[N-（3,5-Difluorophenacetyl）-L-alanyl]-S-phenylglycine t-butyl ester （〉 10 nmol/L） prolonged the survival of PC12 cells after Aβ25-35 induction, decreased the expression of apoptosis-related proteins caspase-3, -8, -9, increased the activity of oxidative stress-related superoxide dismutase and catalase, inhibited the production of active oxygen, and reduced nuclear factor kappa B expression. This study indicates that the Notch-1 signaling pathway plays a pivotal role in Aβ25-35-induced PC12 apoptosis.展开更多
The Na+ - K+ ATPase is an enzyme responsible for the active transport of Na+ and K+ in most eukaryotic cells. The aim of the present study was to determine the effect of Tachykinin neuropeptide, Neurokinin B (NKB) and...The Na+ - K+ ATPase is an enzyme responsible for the active transport of Na+ and K+ in most eukaryotic cells. The aim of the present study was to determine the effect of Tachykinin neuropeptide, Neurokinin B (NKB) and Amyloid beta fragment Aβ (25 - 35) on 17β estradiol (E2) treated aging female rat brain synaptosomes of different age groups, by assaying Na+ - K+ ATPase enzyme activity. An in vitro incubation of isolated synaptosomes with Aβ (25 - 35) showed toxic effects while NKB showed stimulating effect on the Na+ - K+ ATPase activity, and the combined NKB + Aβ (25 - 35) incubations showed a partial effect as compared to the Aβ (25 - 35) alone. To understand whether E2 affects the expression of Na+ - K+ ATPase molecules, we examined the expression of Na+ - K+ ATPase subunit α1 and β2 in E2 treated aging female rat brain synaptosomes. The enzyme was quantified by SDS PAGE in control and E2 treated rat brain. We observed that the expression of α1 and β2 Na+ - K+ ATPase molecules increased and reversed to a normal level in E2 treated synaptosomes. These results confirmed that E2 increased turnover of Na+ - K+ ATPase molecules in aging rat brain. The present findings also suggest a possible role of NKB with E2 in the age related changes in the brain.展开更多
A progressive neurodegenerative disease,Alzheimer’s disease(AD).Studies suggest that highly expressed protein isoaspartate methyltransferase 1(PCMT1)in brain tissue.In the current study,we explored the effects of neu...A progressive neurodegenerative disease,Alzheimer’s disease(AD).Studies suggest that highly expressed protein isoaspartate methyltransferase 1(PCMT1)in brain tissue.In the current study,we explored the effects of neural stem cell-conditioned medium(NSC-CDM)on the PCMT1/MST1 pathway to alleviate Aβ_(25-35)-induced damage in SH-SY5Y cells.Our data suggested that Aβ_(25-35) markedly inhibited cell viability.NSC-CDM or Neural stem cell-complete medium(NSC-CPM)had a suppression effect on toxicity when treatment with Aβ_(25-35),with a greater effect observed with NSC-CDM.Aβ_(25-35)+NSC-CDM group exhibited an increase in PCMT1 expression.sh-PCMT1 markedly decreased cell proliferation and suppressed the protective role of NSC-CDM through the induction of apoptosis and improved p-MST1 expression.Overexpression of PCMT1 reversed the Aβ_(25-35)-induced decrease in cell proliferation and apoptosis.In summary,our findings suggest that NSC-CDM corrects the Aβ_(25-35)-induced damage to cells by improving PCMT1 expressions,which in turn reduces phosphorylation of MST1.展开更多
The brain experiences structural, molecular and functional alterations during aging. In aging brain tissue, the oxidative stress increases due to decreased activity of antioxidant enzymes and increased oxidative stres...The brain experiences structural, molecular and functional alterations during aging. In aging brain tissue, the oxidative stress increases due to decreased activity of antioxidant enzymes and increased oxidative stress leading to neurodegeneration associated with excitotoxicity. In the present study, we observed the effect of tachykinin neuropeptide Neurokinin B (NKB) and amyloid beta fragment Aβ (25 -?35) on the activity of Acetylcholine esterase (AChE) and Lipid peroxidation (LPO) in brains of 17β estradiol (E2) treated aging female rat synaptosomes of different age groups. An in-vitro incubation of E2 treated brain synaptosomes with Aβ (25 -?35) showed toxic effects on all the parameters. The treatment of NKB and combined NKB and Aβ (25 -?35) increased the AChE enzyme activity and decreased the level of LPO in E2 treated aging rats. The treatment of NKB and combined NKB and Aβ (25 - 35) in a concentration dependent manner reversed the effects of aging and Aβ (25 -?35) on AChE and LPO. The present finding suggests that E2 along with NKB reverse aging and Aβ (25 -?35) induced toxicity as well as AChE and LPO levels. The results of the current study showed a possible beneficial role of NKB with E2 inthe age related neurological diseases.展开更多
Aging is the leading risk factor for neurodegenerative diseases and oxidative stress involved in the pathophysiology of these diseases. These changes increase during menopausal condition in females when the level of e...Aging is the leading risk factor for neurodegenerative diseases and oxidative stress involved in the pathophysiology of these diseases. These changes increase during menopausal condition in females when the level of estradiol is decreased. The aim of the present study was to determine the effect of tachykinin neuropeptide, Neurokinin B (NKB) and Amyloid beta fragment Aβ (25 -?35) on 17β estradiol (E2) treated aging female rat synaptosomes of different age groups. Aging brain functions were assayed by measuring the activities of antioxidant enzymes—superoxide dismutase (SOD) and monoamine oxidase (MAO) with neuropeptides. An in-vitro incubation of Aβ (25 -?35) in E2 treated brain synaptosomes showed toxic effects on all the parameters. However, NKB and NKB combined with Aβ (25 35) showed stimulating effects in E2 treated rat brain synaptosomes. In the present study, an increase in activity of SOD and decrease in the level of MAO, in the presence of NKB and combined NKB and Aβ in E2 treated brain synaptosomes of aging rats. This study elucidates that treatment of NKB and Aβ with E2 incombination exerts more protective influence than their individual application, against excitotoxicity in age related changes.展开更多
PC12 cell injury was induced using 20 μM amyloid β-protein 25-35 to establish a model of Alzheimer＇s disease. The cells were then treated with 5, 10, and 25 μM Schisandrin B. Methylthiazolyldiphenyl-tetrazolium br...PC12 cell injury was induced using 20 μM amyloid β-protein 25-35 to establish a model of Alzheimer＇s disease. The cells were then treated with 5, 10, and 25 μM Schisandrin B. Methylthiazolyldiphenyl-tetrazolium bromide assays and Hoechst 33342 staining results showed that with increasing Schisandrin B concentration, the survival rate of PC12 cells injured by amyloid β-protein 25-35 gradually increased and the rate of apoptosis gradually decreased. Reverse transcription-PCR, immunocytochemical staining and western blot results showed that with increasing Schisandrin B concentration, the mRNA and protein expression of vacuolar protein sorting 35 and amyloid precursor protein were gradually decreased. Vacuolar protein sorting 35 and amyloid precursor protein showed a consistent trend for change. These findings suggest that 5, 10, and 25 μM Schisandrin B antagonizes the cellular injury induced by amyloid β-protein 25-35 in a dose-dependent manner. This may be caused by decreasing the expression of vacuolar protein sorting 35 and amyloid precursor protein.展开更多
Oxidative stress has an important role in the development of Alzheimer＇s disease （AD）. Beta amyloid protein 25-35 （Aβ25-35） can generate oxygen free radicals, and MCI-186 （3-methyl-l-phenyl-2-pyrazolin-5-one, e...Oxidative stress has an important role in the development of Alzheimer＇s disease （AD）. Beta amyloid protein 25-35 （Aβ25-35） can generate oxygen free radicals, and MCI-186 （3-methyl-l-phenyl-2-pyrazolin-5-one, edaravone） can specifically eliminate hydroxyl radicals. The present study introduced Aβ25-35 into PC12 cells to establish a cell model of AD, and investigated the neuroprotective effects of MCI-186 on AD. Results showed that MCI-186 had a positive effect on the prevention and treatment of AD by inhibiting protein oxidative products, advanced glycation end products, lipid oxidative end products and DNA oxidative damage in PC12 cells induced by Aβ25-35.展开更多
文摘Recent studies have demonstrated that Notch-1 expression is increased in the hippocampus of Alzheimer＇s disease patients. We speculate that Notch-1 signaling may be involved in PC12 cell apoptosis induced by amyloid beta-peptide （25-35） （Aβ25-35）. In the present study, PC12 cells were cultured with different doses （0, 0.1, 1.0, 10 and 100 nmol/L） of N-[N-（3,5-Difluorophenacetyl）-L-alanyl]-S-phenylglycine t-butyl ester, a Notch-1 signaling pathway inhibitor, for 30 minutes. Then cultured cells were induced with Aβ25-3s for 48 hours. Pretreatment of PC12 cells with high doses of N-[N-（3,5-Difluorophenacetyl）-L-alanyl]-S-phenylglycine t-butyl ester （〉 10 nmol/L） prolonged the survival of PC12 cells after Aβ25-35 induction, decreased the expression of apoptosis-related proteins caspase-3, -8, -9, increased the activity of oxidative stress-related superoxide dismutase and catalase, inhibited the production of active oxygen, and reduced nuclear factor kappa B expression. This study indicates that the Notch-1 signaling pathway plays a pivotal role in Aβ25-35-induced PC12 apoptosis.
文摘The Na+ - K+ ATPase is an enzyme responsible for the active transport of Na+ and K+ in most eukaryotic cells. The aim of the present study was to determine the effect of Tachykinin neuropeptide, Neurokinin B (NKB) and Amyloid beta fragment Aβ (25 - 35) on 17β estradiol (E2) treated aging female rat brain synaptosomes of different age groups, by assaying Na+ - K+ ATPase enzyme activity. An in vitro incubation of isolated synaptosomes with Aβ (25 - 35) showed toxic effects while NKB showed stimulating effect on the Na+ - K+ ATPase activity, and the combined NKB + Aβ (25 - 35) incubations showed a partial effect as compared to the Aβ (25 - 35) alone. To understand whether E2 affects the expression of Na+ - K+ ATPase molecules, we examined the expression of Na+ - K+ ATPase subunit α1 and β2 in E2 treated aging female rat brain synaptosomes. The enzyme was quantified by SDS PAGE in control and E2 treated rat brain. We observed that the expression of α1 and β2 Na+ - K+ ATPase molecules increased and reversed to a normal level in E2 treated synaptosomes. These results confirmed that E2 increased turnover of Na+ - K+ ATPase molecules in aging rat brain. The present findings also suggest a possible role of NKB with E2 in the age related changes in the brain.
文摘A progressive neurodegenerative disease,Alzheimer’s disease(AD).Studies suggest that highly expressed protein isoaspartate methyltransferase 1(PCMT1)in brain tissue.In the current study,we explored the effects of neural stem cell-conditioned medium(NSC-CDM)on the PCMT1/MST1 pathway to alleviate Aβ_(25-35)-induced damage in SH-SY5Y cells.Our data suggested that Aβ_(25-35) markedly inhibited cell viability.NSC-CDM or Neural stem cell-complete medium(NSC-CPM)had a suppression effect on toxicity when treatment with Aβ_(25-35),with a greater effect observed with NSC-CDM.Aβ_(25-35)+NSC-CDM group exhibited an increase in PCMT1 expression.sh-PCMT1 markedly decreased cell proliferation and suppressed the protective role of NSC-CDM through the induction of apoptosis and improved p-MST1 expression.Overexpression of PCMT1 reversed the Aβ_(25-35)-induced decrease in cell proliferation and apoptosis.In summary,our findings suggest that NSC-CDM corrects the Aβ_(25-35)-induced damage to cells by improving PCMT1 expressions,which in turn reduces phosphorylation of MST1.
文摘The brain experiences structural, molecular and functional alterations during aging. In aging brain tissue, the oxidative stress increases due to decreased activity of antioxidant enzymes and increased oxidative stress leading to neurodegeneration associated with excitotoxicity. In the present study, we observed the effect of tachykinin neuropeptide Neurokinin B (NKB) and amyloid beta fragment Aβ (25 -?35) on the activity of Acetylcholine esterase (AChE) and Lipid peroxidation (LPO) in brains of 17β estradiol (E2) treated aging female rat synaptosomes of different age groups. An in-vitro incubation of E2 treated brain synaptosomes with Aβ (25 -?35) showed toxic effects on all the parameters. The treatment of NKB and combined NKB and Aβ (25 -?35) increased the AChE enzyme activity and decreased the level of LPO in E2 treated aging rats. The treatment of NKB and combined NKB and Aβ (25 - 35) in a concentration dependent manner reversed the effects of aging and Aβ (25 -?35) on AChE and LPO. The present finding suggests that E2 along with NKB reverse aging and Aβ (25 -?35) induced toxicity as well as AChE and LPO levels. The results of the current study showed a possible beneficial role of NKB with E2 inthe age related neurological diseases.
文摘Aging is the leading risk factor for neurodegenerative diseases and oxidative stress involved in the pathophysiology of these diseases. These changes increase during menopausal condition in females when the level of estradiol is decreased. The aim of the present study was to determine the effect of tachykinin neuropeptide, Neurokinin B (NKB) and Amyloid beta fragment Aβ (25 -?35) on 17β estradiol (E2) treated aging female rat synaptosomes of different age groups. Aging brain functions were assayed by measuring the activities of antioxidant enzymes—superoxide dismutase (SOD) and monoamine oxidase (MAO) with neuropeptides. An in-vitro incubation of Aβ (25 -?35) in E2 treated brain synaptosomes showed toxic effects on all the parameters. However, NKB and NKB combined with Aβ (25 35) showed stimulating effects in E2 treated rat brain synaptosomes. In the present study, an increase in activity of SOD and decrease in the level of MAO, in the presence of NKB and combined NKB and Aβ in E2 treated brain synaptosomes of aging rats. This study elucidates that treatment of NKB and Aβ with E2 incombination exerts more protective influence than their individual application, against excitotoxicity in age related changes.
基金supported by the National 985 Project "linguistic science technology and the construction of interdisciplinary innovation platform in current society",No.985yk002the National 985 Project "cognitive and neural information science platform",No.904273258
文摘PC12 cell injury was induced using 20 μM amyloid β-protein 25-35 to establish a model of Alzheimer＇s disease. The cells were then treated with 5, 10, and 25 μM Schisandrin B. Methylthiazolyldiphenyl-tetrazolium bromide assays and Hoechst 33342 staining results showed that with increasing Schisandrin B concentration, the survival rate of PC12 cells injured by amyloid β-protein 25-35 gradually increased and the rate of apoptosis gradually decreased. Reverse transcription-PCR, immunocytochemical staining and western blot results showed that with increasing Schisandrin B concentration, the mRNA and protein expression of vacuolar protein sorting 35 and amyloid precursor protein were gradually decreased. Vacuolar protein sorting 35 and amyloid precursor protein showed a consistent trend for change. These findings suggest that 5, 10, and 25 μM Schisandrin B antagonizes the cellular injury induced by amyloid β-protein 25-35 in a dose-dependent manner. This may be caused by decreasing the expression of vacuolar protein sorting 35 and amyloid precursor protein.
基金the Talent Introduction Project of Affili-ated Hospital of Jiangsu University,No.jdfyRC 2008003
文摘Oxidative stress has an important role in the development of Alzheimer＇s disease （AD）. Beta amyloid protein 25-35 （Aβ25-35） can generate oxygen free radicals, and MCI-186 （3-methyl-l-phenyl-2-pyrazolin-5-one, edaravone） can specifically eliminate hydroxyl radicals. The present study introduced Aβ25-35 into PC12 cells to establish a cell model of AD, and investigated the neuroprotective effects of MCI-186 on AD. Results showed that MCI-186 had a positive effect on the prevention and treatment of AD by inhibiting protein oxidative products, advanced glycation end products, lipid oxidative end products and DNA oxidative damage in PC12 cells induced by Aβ25-35.
