Oat contains different components that possess antioxidant properties;no study to date has addressed the antioxidant effect of the extract of oat bran on the cellular level.Therefore,the present study focuses on the i...Oat contains different components that possess antioxidant properties;no study to date has addressed the antioxidant effect of the extract of oat bran on the cellular level.Therefore,the present study focuses on the investigation of the protective effect of oat bran extract by enzymatic hydrolysates on human dermal fibroblast injury induced by hydrogen peroxide(H2O2).Kjeldahl determination,phenol-sulfuric acid method,and high-performance liquid chromatography(HPLC) analysis indicated that the enzymatic products of oat bran contain a protein amount of 71.93%,of which 97.43% are peptides with a molecular range from 438.56 to 1 301.01 Da.Assays for 1,1-diphenyl-2-picrylhydrazyl(DPPH) radical scavenging activity indicate that oat peptide-rich extract has a direct and concentration-dependent antioxidant activity.3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT) colorimetric assay and the TdT-mediated digoxigenin-dUTP nick-end labeling(TUNEL) assay for apoptosis showed that administration of H2O2 in human dermal fibroblasts caused cell damage and apoptosis.Pre-incubation of human dermal fibroblasts with the Oatp for 24 h markedly inhibited human dermal fibroblast injury induced by H2O2,but application oat peptides with H2O2 at same time did not.Pre-treatment of human dermal fibroblasts with Oatp significantly reversed the H2O2-induced decrease of superoxide dismutase(SOD) and the inhibition of malondialdehyde(MDA).The results demonstrate that oat peptides possess antioxidant activity and are effective against H2O2-induced human dermal fibroblast injury by the enhanced activity of SOD and decrease in MDA level.Our results suggest that oat bran will have the potential to be further explored as an antioxidant functional food in the prevention of aging-related skin injury.展开更多
The sigma-1 receptor is a molecular chaperone protein highly enriched in the brain.Recent studies linked it to many diseases,such as drug addition,Alzheimer’s disease,stroke,depression,and even cancer.Sigma-1 recepto...The sigma-1 receptor is a molecular chaperone protein highly enriched in the brain.Recent studies linked it to many diseases,such as drug addition,Alzheimer’s disease,stroke,depression,and even cancer.Sigma-1 receptor is enriched in lipid rafts,which are membrane microdomains essential in signaling processes.One of those signaling processes is ADAM17-and ADAM10-dependent ectodomain shedding.By using an alkaline phosphatase tagged substrate reporter system,we have shown that ADAM10-dependent BTC shedding was very sensitive to both membrane lipid component change and sigma-1 receptor agonist DHEAS treatment while ADAM17-dependent HB-EGF shedding was not;and overexpression of sigma-1 receptor diminished ADAM17-and ADAM10-dependent shedding.Our results indicate that sigma-1 receptor plays an important role in modifying the function of transmembrane proteases.展开更多
The family of voltage-gated potassium Kv2 channels consists of the Kv2.1 and Kv2.2 subtypes.Kv2.1 is constitutively highly phosphorylated in neurons and its function relies on its phosphorylation state.Whether the fun...The family of voltage-gated potassium Kv2 channels consists of the Kv2.1 and Kv2.2 subtypes.Kv2.1 is constitutively highly phosphorylated in neurons and its function relies on its phosphorylation state.Whether the function of Kv2.2 is also dependent on its phosphorylation state remains unknown.Here,we investigated whether Kv2.2 channels can be phosphorylated by protein kinase C(PKC)and examined the effects of PKC-induced phosphorylation on their activity and function.Activation of PKC inhibited Kv2.2 currents and altered their steadystate activation in HEK293 cells.Point mutations and specific antibodies against phosphorylated S481 or S488 demonstrated the importance of these residues for the PKC-dependent modulation of Kv2.2.In layer Ⅱ pyramidal neurons in cortical slices,activation of PKC similarly regulated native Kv2.2 channels and simultaneously reduced the frequency of action potentials.In conclusion,this study provides the first evidence to our knowledge that PKC-induced phosphorylation of the Kv2.2 channel controls the excitability of cortical pyramidal neurons.展开更多
Cyproheptadine (CPH), a first-generation anti- histamine, enhances the delayed rectifier outward K+ current (IK) in mouse cortical neurons through a sigma-1 receptor-mediated protein kinase A pathway. In this stu...Cyproheptadine (CPH), a first-generation anti- histamine, enhances the delayed rectifier outward K+ current (IK) in mouse cortical neurons through a sigma-1 receptor-mediated protein kinase A pathway. In this study, we aimed to determine the effects of CPH on neuronal excitability in current-clamped pyramidal neurons in mouse medial prefrontal cortex slices. CPH (10 μmol/L) significantly reduced the current density required to generate action potentials (APs) and increased the instan- taneous frequency evoked by a depolarizing current. CPH also depolarized the resting membrane potential (RMP), decreased the delay time to elicit an AP, and reduced the spike threshold potential. This effect of CPH was mim- icked by a sigma-1 receptor agonist and eliminated by an antagonist. Application of tetraethylammonium (TEA) to block IK channels hyperpolarized the RMP and reduced the instantaneous frequency of APs. TEA eliminated the effects of CPH on AP frequency and delay time, but had no effect on spike threshold or RMP. The current-voltage relationship showed that CPH increased the membrane depolarization in response to positive current pulses and hyperpolarization in response to negative current pulses, suggesting that other types of membrane ion channels might also be affected by CPH. These results suggest that CPH increases the excitability of medial prefrontal cortex neurons by regulating TEA-sensitive IK channels as well as other TEA-insensitive K+ channels, probably ID and inward-rectifier Kir channels. This effect of CPH may explain its apparent clinical efficacy as an antidepressant and antipsychotic.展开更多
Erratum to:Protein Cell 2012,3(2):153-159 DOI 10.1007/s13238-012-2006-9 Two mistakes in Fig.3A and 4A,respectively,were made due to typesetting errors.Figure 3A,on the left column of page 156,should be cor-rected as f...Erratum to:Protein Cell 2012,3(2):153-159 DOI 10.1007/s13238-012-2006-9 Two mistakes in Fig.3A and 4A,respectively,were made due to typesetting errors.Figure 3A,on the left column of page 156,should be cor-rected as follows.Figure 4A,on the left column of page 157,should be cor-rected as follows.展开更多
文摘Oat contains different components that possess antioxidant properties;no study to date has addressed the antioxidant effect of the extract of oat bran on the cellular level.Therefore,the present study focuses on the investigation of the protective effect of oat bran extract by enzymatic hydrolysates on human dermal fibroblast injury induced by hydrogen peroxide(H2O2).Kjeldahl determination,phenol-sulfuric acid method,and high-performance liquid chromatography(HPLC) analysis indicated that the enzymatic products of oat bran contain a protein amount of 71.93%,of which 97.43% are peptides with a molecular range from 438.56 to 1 301.01 Da.Assays for 1,1-diphenyl-2-picrylhydrazyl(DPPH) radical scavenging activity indicate that oat peptide-rich extract has a direct and concentration-dependent antioxidant activity.3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT) colorimetric assay and the TdT-mediated digoxigenin-dUTP nick-end labeling(TUNEL) assay for apoptosis showed that administration of H2O2 in human dermal fibroblasts caused cell damage and apoptosis.Pre-incubation of human dermal fibroblasts with the Oatp for 24 h markedly inhibited human dermal fibroblast injury induced by H2O2,but application oat peptides with H2O2 at same time did not.Pre-treatment of human dermal fibroblasts with Oatp significantly reversed the H2O2-induced decrease of superoxide dismutase(SOD) and the inhibition of malondialdehyde(MDA).The results demonstrate that oat peptides possess antioxidant activity and are effective against H2O2-induced human dermal fibroblast injury by the enhanced activity of SOD and decrease in MDA level.Our results suggest that oat bran will have the potential to be further explored as an antioxidant functional food in the prevention of aging-related skin injury.
基金by the Shanghai Leading Academic Discipline Project(B111)NSFC(Grant No.30800322)+4 种基金Shanghai Pujiang Program(08PJ1401300)Ministry of Education Start Fund to Returned Overseas ScholarsMinistry of Education Research Fund for New Teachers in Doctoral Program of Higher Educational InstitutesNational Basic Research Program of China(973 Program)(Grant No.2011CB503703)and Institute of Brain Sciences at Fudan University.The funders had no role in study design,data collection and analysis,decision to publish,or preparation of the manuscript.
文摘The sigma-1 receptor is a molecular chaperone protein highly enriched in the brain.Recent studies linked it to many diseases,such as drug addition,Alzheimer’s disease,stroke,depression,and even cancer.Sigma-1 receptor is enriched in lipid rafts,which are membrane microdomains essential in signaling processes.One of those signaling processes is ADAM17-and ADAM10-dependent ectodomain shedding.By using an alkaline phosphatase tagged substrate reporter system,we have shown that ADAM10-dependent BTC shedding was very sensitive to both membrane lipid component change and sigma-1 receptor agonist DHEAS treatment while ADAM17-dependent HB-EGF shedding was not;and overexpression of sigma-1 receptor diminished ADAM17-and ADAM10-dependent shedding.Our results indicate that sigma-1 receptor plays an important role in modifying the function of transmembrane proteases.
基金supported by the National Natural Science Foundation of China(31771282)the China Postdoctoral Science Foundation(BX20200093 and 2021M690038).
文摘The family of voltage-gated potassium Kv2 channels consists of the Kv2.1 and Kv2.2 subtypes.Kv2.1 is constitutively highly phosphorylated in neurons and its function relies on its phosphorylation state.Whether the function of Kv2.2 is also dependent on its phosphorylation state remains unknown.Here,we investigated whether Kv2.2 channels can be phosphorylated by protein kinase C(PKC)and examined the effects of PKC-induced phosphorylation on their activity and function.Activation of PKC inhibited Kv2.2 currents and altered their steadystate activation in HEK293 cells.Point mutations and specific antibodies against phosphorylated S481 or S488 demonstrated the importance of these residues for the PKC-dependent modulation of Kv2.2.In layer Ⅱ pyramidal neurons in cortical slices,activation of PKC similarly regulated native Kv2.2 channels and simultaneously reduced the frequency of action potentials.In conclusion,this study provides the first evidence to our knowledge that PKC-induced phosphorylation of the Kv2.2 channel controls the excitability of cortical pyramidal neurons.
基金supported by the National Natural Science Foundation of China(31370827)the Shanghai Leading Academic Discipline Project [B111]
文摘Cyproheptadine (CPH), a first-generation anti- histamine, enhances the delayed rectifier outward K+ current (IK) in mouse cortical neurons through a sigma-1 receptor-mediated protein kinase A pathway. In this study, we aimed to determine the effects of CPH on neuronal excitability in current-clamped pyramidal neurons in mouse medial prefrontal cortex slices. CPH (10 μmol/L) significantly reduced the current density required to generate action potentials (APs) and increased the instan- taneous frequency evoked by a depolarizing current. CPH also depolarized the resting membrane potential (RMP), decreased the delay time to elicit an AP, and reduced the spike threshold potential. This effect of CPH was mim- icked by a sigma-1 receptor agonist and eliminated by an antagonist. Application of tetraethylammonium (TEA) to block IK channels hyperpolarized the RMP and reduced the instantaneous frequency of APs. TEA eliminated the effects of CPH on AP frequency and delay time, but had no effect on spike threshold or RMP. The current-voltage relationship showed that CPH increased the membrane depolarization in response to positive current pulses and hyperpolarization in response to negative current pulses, suggesting that other types of membrane ion channels might also be affected by CPH. These results suggest that CPH increases the excitability of medial prefrontal cortex neurons by regulating TEA-sensitive IK channels as well as other TEA-insensitive K+ channels, probably ID and inward-rectifier Kir channels. This effect of CPH may explain its apparent clinical efficacy as an antidepressant and antipsychotic.
文摘Erratum to:Protein Cell 2012,3(2):153-159 DOI 10.1007/s13238-012-2006-9 Two mistakes in Fig.3A and 4A,respectively,were made due to typesetting errors.Figure 3A,on the left column of page 156,should be cor-rected as follows.Figure 4A,on the left column of page 157,should be cor-rected as follows.