The histone deacetylase inhibitor, trichostatin A, is used to treat Alzheimer’s disease and can improve learning and memory but its underlying mechanism of action is unknown. To determine whether the therapeutic effe...The histone deacetylase inhibitor, trichostatin A, is used to treat Alzheimer’s disease and can improve learning and memory but its underlying mechanism of action is unknown. To determine whether the therapeutic effect of trichostatin A on Alzheimer’s disease is associated with the nuclear factor erythroid 2-related factor 2(Nrf2) and Kelch-like epichlorohydrin-related protein-1(Keap1) signaling pathway, amyloid β-peptide 25–35(Aβ25–35) was used to induce Alzheimer’s disease-like pathological changes in SH-SY5 Y neuroblastoma cells. Cells were then treated with trichostatin A. The effects of trichostatin A on the expression of Keap1 and Nrf2 were detected by real-time quantitative polymerase chain reaction, western blot assays and immunofluorescence. Total antioxidant capacity and autophagy activity were evaluated by total antioxidant capacity assay kit and light chain 3-I/II levels, respectively. We found that trichostatin A increased cell viability and Nrf2 expression, and decreased Keap1 expression in SH-SY5 Y cells. Furthermore, trichostatin A increased the expression of Nrf2-related target genes, such as superoxide dismutase, NAD(P)H quinone dehydrogenase 1 and glutathione S-transferase, thereby increasing the total antioxidant capacity of SH-SY5 Y cells and inhibiting amyloid β-peptide-induced autophagy. Knockdown of Keap1 in SH-SY5 Y cells further increased trichostatin A-induced Nrf2 expression. These results indicate that the therapeutic effect of trichostatin A on Alzheimer’s disease is associated with the Keap1-Nrf2 pathway. The mechanism for this action may be that trichostatin A increases cell viability and the antioxidant capacity of SH-SY5 Y cells by alleviating Keap1-mediated inhibition Nrf2 signaling, thereby alleviating amyloid β-peptide-induced cell damage.展开更多
The regulatory mechanisms of cytoplasmic Ca2+after myocardial infarction-induced Ca2+overload involve secretory pathway Ca2+-ATPase 1 and the Golgi apparatus and are well understood.However,the effect of Golgi apparat...The regulatory mechanisms of cytoplasmic Ca2+after myocardial infarction-induced Ca2+overload involve secretory pathway Ca2+-ATPase 1 and the Golgi apparatus and are well understood.However,the effect of Golgi apparatus on Ca2+overload after cerebral ischemia and reperfusion remains unclear.Four-vessel occlusion rats were used as animal models of cerebral ischemia.The expression of secretory pathway Ca2+-ATPase 1 in the cortex and hippocampus was detected by immunoblotting,and Ca2+concentrations in the cytoplasm and Golgi vesicles were determined.Results showed an overload of cytoplasmic Ca2+during ischemia and reperfusion that reached a peak after reperfusion.Levels of Golgi Ca2+showed an opposite effect.The expression of Golgi-specific secretory pathway Ca2+-ATPase 1 in the cortex and hippocampus decreased before ischemia and reperfusion,and increased after reperfusion for 6 hours.This variation was similar to the alteration of calcium in separated Golgi vesicles.These results indicate that the Golgi apparatus participates in the formation and alleviation of calcium overload,and that secretory pathway Ca2+-ATPase 1 tightly responds to ischemia and reperfusion in nerve cells.Thus,we concluded that secretory pathway Ca2+-ATPase 1 plays an essential role in cytosolic calcium regulation and its expression can be used as a marker of Golgi stress,responding to cerebral ischemia and reperfusion.The secretory pathway Ca2+-ATPase 1 can be an important neuroprotective target of ischemic stroke.展开更多
Objective： Light quality has effect on the accumulation of gypenosides in the medicinal plant Gynosternma pentaphyllum in the family Cucurbitaceae, while the squalene synthase （SS） and squalene epoxidase （SE） are...Objective： Light quality has effect on the accumulation of gypenosides in the medicinal plant Gynosternma pentaphyllum in the family Cucurbitaceae, while the squalene synthase （SS） and squalene epoxidase （SE） are the key enzymes for gypenoside biosynthesis, The objective of this study was to elucidate the rela- tionship between light quality and biosynthesis key enzyme involving the regulation of gypenoside accu- mulation. Methods： The content of total gypenosides was measured by colorimetric method and the expression of SS and SE gene was determined by quantitative Real-time PCR in the seedlings of G. pentaphyllum which were grown with different light quality. Results： Light quality showed remarkable impacts on the accumulation of total gypenosides. The highest content of total gypenosides in the plant under red light condition was determined, followed by blue light and white light, while the lowest content was recorded under dark condition, qRT-PCR analysis proved that the expression levels of SS and SE genes were also affected by light quality. The high-level gene expressions of SS and SE were found in the plant under red light condition, followed by blue light, with the least content in darkness. The statistical analysis revealed that the total gypenosides were significantly different in different light treatment and the content of total gypenosides was positively related to the expression of SS and SE genes. Conclusions： Light quality regulates gypenoside accumulation via altering the expression of SS and SE in G. pentaphyllum.展开更多
文摘The histone deacetylase inhibitor, trichostatin A, is used to treat Alzheimer’s disease and can improve learning and memory but its underlying mechanism of action is unknown. To determine whether the therapeutic effect of trichostatin A on Alzheimer’s disease is associated with the nuclear factor erythroid 2-related factor 2(Nrf2) and Kelch-like epichlorohydrin-related protein-1(Keap1) signaling pathway, amyloid β-peptide 25–35(Aβ25–35) was used to induce Alzheimer’s disease-like pathological changes in SH-SY5 Y neuroblastoma cells. Cells were then treated with trichostatin A. The effects of trichostatin A on the expression of Keap1 and Nrf2 were detected by real-time quantitative polymerase chain reaction, western blot assays and immunofluorescence. Total antioxidant capacity and autophagy activity were evaluated by total antioxidant capacity assay kit and light chain 3-I/II levels, respectively. We found that trichostatin A increased cell viability and Nrf2 expression, and decreased Keap1 expression in SH-SY5 Y cells. Furthermore, trichostatin A increased the expression of Nrf2-related target genes, such as superoxide dismutase, NAD(P)H quinone dehydrogenase 1 and glutathione S-transferase, thereby increasing the total antioxidant capacity of SH-SY5 Y cells and inhibiting amyloid β-peptide-induced autophagy. Knockdown of Keap1 in SH-SY5 Y cells further increased trichostatin A-induced Nrf2 expression. These results indicate that the therapeutic effect of trichostatin A on Alzheimer’s disease is associated with the Keap1-Nrf2 pathway. The mechanism for this action may be that trichostatin A increases cell viability and the antioxidant capacity of SH-SY5 Y cells by alleviating Keap1-mediated inhibition Nrf2 signaling, thereby alleviating amyloid β-peptide-induced cell damage.
基金supported by the National Natural Science Foundation of China,No.81171239
文摘The regulatory mechanisms of cytoplasmic Ca2+after myocardial infarction-induced Ca2+overload involve secretory pathway Ca2+-ATPase 1 and the Golgi apparatus and are well understood.However,the effect of Golgi apparatus on Ca2+overload after cerebral ischemia and reperfusion remains unclear.Four-vessel occlusion rats were used as animal models of cerebral ischemia.The expression of secretory pathway Ca2+-ATPase 1 in the cortex and hippocampus was detected by immunoblotting,and Ca2+concentrations in the cytoplasm and Golgi vesicles were determined.Results showed an overload of cytoplasmic Ca2+during ischemia and reperfusion that reached a peak after reperfusion.Levels of Golgi Ca2+showed an opposite effect.The expression of Golgi-specific secretory pathway Ca2+-ATPase 1 in the cortex and hippocampus decreased before ischemia and reperfusion,and increased after reperfusion for 6 hours.This variation was similar to the alteration of calcium in separated Golgi vesicles.These results indicate that the Golgi apparatus participates in the formation and alleviation of calcium overload,and that secretory pathway Ca2+-ATPase 1 tightly responds to ischemia and reperfusion in nerve cells.Thus,we concluded that secretory pathway Ca2+-ATPase 1 plays an essential role in cytosolic calcium regulation and its expression can be used as a marker of Golgi stress,responding to cerebral ischemia and reperfusion.The secretory pathway Ca2+-ATPase 1 can be an important neuroprotective target of ischemic stroke.
基金financially supported by the National Natural Science Foundation of China (31760044,31260039)Key Course of Hunan Province (Ecology),Jishou University (2015005)
文摘Objective： Light quality has effect on the accumulation of gypenosides in the medicinal plant Gynosternma pentaphyllum in the family Cucurbitaceae, while the squalene synthase （SS） and squalene epoxidase （SE） are the key enzymes for gypenoside biosynthesis, The objective of this study was to elucidate the rela- tionship between light quality and biosynthesis key enzyme involving the regulation of gypenoside accu- mulation. Methods： The content of total gypenosides was measured by colorimetric method and the expression of SS and SE gene was determined by quantitative Real-time PCR in the seedlings of G. pentaphyllum which were grown with different light quality. Results： Light quality showed remarkable impacts on the accumulation of total gypenosides. The highest content of total gypenosides in the plant under red light condition was determined, followed by blue light and white light, while the lowest content was recorded under dark condition, qRT-PCR analysis proved that the expression levels of SS and SE genes were also affected by light quality. The high-level gene expressions of SS and SE were found in the plant under red light condition, followed by blue light, with the least content in darkness. The statistical analysis revealed that the total gypenosides were significantly different in different light treatment and the content of total gypenosides was positively related to the expression of SS and SE genes. Conclusions： Light quality regulates gypenoside accumulation via altering the expression of SS and SE in G. pentaphyllum.
