Background Chronic intermittent hypoxia （CIH） is the most important pathophysiologic feature of sleep apnea syndrome （SAS）. To explore the relationship between SAS and dementia, the effects of CIH on the expressio...Background Chronic intermittent hypoxia （CIH） is the most important pathophysiologic feature of sleep apnea syndrome （SAS）. To explore the relationship between SAS and dementia, the effects of CIH on the expression of Nip3, neuron apoptosis and β-amyloid protein deposit in the brain cortex of the frontal lobe of mice were evaluated in this study.Methods Thirty male ICRmice＇were divided into four groups： control group （A, n=-10, sham hypoxia/reoxygenation）, 2 weeks CIH group （B, n=5）, 4 weeks CIH group （C, n=-5）, and 8 weeks CIH group （D, n=10）. The ICR mice were placed in a chamber and exposed to intermittent hypoxia （oxygen concentration changed periodically from （21.72±0.55）% to （6.84±0.47）% every two minutes, eight hours per day）. Neuron apoptosis of the cortex of the frontal lobe was detected by means of terminal deoxy-nucleotidyl transferase-mediated in situ end labeling （TUNEL）. Immunohistochemical staining was performed for measuring expression of Nip3 and β-amyloid protein. The ultrastructure of neurons was observed under a transmission electron microscope.Results TUNEL positive neurons in each square millimeter in the cortex of the frontal lobe were categorized by median or Riinto group A （1, 5.5）, group B （133, 13）, group C （252, 21）, and group D （318, 24）. There were significant differences among the above four groups （P=0.000）. The significance test was performed between the control group and each CIH group respectively： group A and B （P 〉0.05）; group A and C （P 〈0.01）; and group A and D （P 〈0.005）. The number of apoptotic neurons kept increasing in the ICR mice under CIH condition, and reached the peak in the group D, but there was no significant difference between groups B and C, between groups B and D, and between groups C and D. Nip3 positive neurons in each square millimeter in the cortex of the frontal lobe in each group were calculated by median or Ri as follows： group A （2, 5.5）, group B （117, 13）, group C （227, 26.2）, and group D（479, 21.4）. There were significant differences among the four groups （P=0.000）. The statistical test was performed between the control group and each CIH group respectively： groups A and B （P 〉0.05）; groups A and C （P〈0.005）; and groups A and D （P 〈0.005）. There was no significant difference between groups B and C, groups B and D, and groups C and D. The expression of Nip3 was closely correlated with neuron apoptosis in the brain （P 〈0.05）. The expression of β-amyloid protein in the brain of mice was negative in all CIH groups and the control group. Ultrastructure observation showed karyopyknosis of nucleus, swelling of chondriosomes, deposit of lipofuscins and degeneration of neural sheath in all CIH groups but not in the control group. Conclusion The results of this study indicate that CIH could up-regulate the expression of Nip3, and result in neuron apoptosis and ultrastructural changes in neurons of the frontal cortex.展开更多
In Arabidopsis, the nodulin 26-like intrinsic protein （NIP） subfamily of aquaporin proteins consists of nine members, five of which （NIP1;1, NIP1;2, NIP5;1, NIP6;1, and NIP7;1） were previously identified to be per...In Arabidopsis, the nodulin 26-like intrinsic protein （NIP） subfamily of aquaporin proteins consists of nine members, five of which （NIP1;1, NIP1;2, NIP5;1, NIP6;1, and NIP7;1） were previously identified to be perme- able to arsenite. However, the roles of NIPs in the root-to-shoot translocation of arsenite in plants remain poorly understood. In this study, using reverse genetic strategies, Arabidopsis NIP3;1 was identified to play an important role in both the arsenic uptake and root-to-shoot distribution under arsenite stress condi- tions. The nip3;1 loss-of-function mutants displayed obvious improvements in arsenite tolerance for aboveground growth and accumulated less arsenic in shoots than those of the wild-type plants, whereas the nip3;1 nip1;1 double mutant showed strong arsenite tolerance and improved growth of both roots and shoots under arsenite stress conditions. A promoter-β-glucuronidase analysis revealed that NIP3; 1 was ex- pressed almost exclusively in roots （with the exception of the root tips）, and heterologous expression in the yeast Saccharomyces cerevisiae demonstrated that NIP3;1 was able to mediate arsenite transport. Taken together, our results suggest that NIP3;1 is involved in arsenite uptake and root-to-shoot translocation in Arabidopsis, probably as a passive and bidirectional arsenite transporter.展开更多
Clinical practice has shown that Parkin is the major causative gene found in an autosomal recessive juvenile parkin-sonism(AR-JP)via Parkin mutations and that the Parkin protein is the core expression product of the P...Clinical practice has shown that Parkin is the major causative gene found in an autosomal recessive juvenile parkin-sonism(AR-JP)via Parkin mutations and that the Parkin protein is the core expression product of the Parkin gene,which itself belongs to an E3 ubiquitin ligase.Since the discovery of the Parkin gene in the late 1990s,researchers in many countries have begun extensive research on this gene and found that in addition to AR-JP,the Parkin gene is associated with many diseases,including type 2 diabetes,leprosy,Alzheimer’s,autism,and cancer.Recent studies have found that the loss or dysfunction of Parkin has a certain relationship with tumorigenesis.In general,the Parkin gene,a well-established tumor suppressor,is deficient and mutated in a variety of malignancies.Parkin overexpres-sion inhibits tumor cell growth and promotes apoptosis.However,the functions of Parkin in tumorigenesis and its regulatory mechanisms are still not fully understood.This article describes the structure,functions,and post-transla-tional modifications of Parkin,and summarizes the recent advances in the tumor suppressive function of Parkin and its underlying mechanisms.展开更多
文摘Background Chronic intermittent hypoxia （CIH） is the most important pathophysiologic feature of sleep apnea syndrome （SAS）. To explore the relationship between SAS and dementia, the effects of CIH on the expression of Nip3, neuron apoptosis and β-amyloid protein deposit in the brain cortex of the frontal lobe of mice were evaluated in this study.Methods Thirty male ICRmice＇were divided into four groups： control group （A, n=-10, sham hypoxia/reoxygenation）, 2 weeks CIH group （B, n=5）, 4 weeks CIH group （C, n=-5）, and 8 weeks CIH group （D, n=10）. The ICR mice were placed in a chamber and exposed to intermittent hypoxia （oxygen concentration changed periodically from （21.72±0.55）% to （6.84±0.47）% every two minutes, eight hours per day）. Neuron apoptosis of the cortex of the frontal lobe was detected by means of terminal deoxy-nucleotidyl transferase-mediated in situ end labeling （TUNEL）. Immunohistochemical staining was performed for measuring expression of Nip3 and β-amyloid protein. The ultrastructure of neurons was observed under a transmission electron microscope.Results TUNEL positive neurons in each square millimeter in the cortex of the frontal lobe were categorized by median or Riinto group A （1, 5.5）, group B （133, 13）, group C （252, 21）, and group D （318, 24）. There were significant differences among the above four groups （P=0.000）. The significance test was performed between the control group and each CIH group respectively： group A and B （P 〉0.05）; group A and C （P 〈0.01）; and group A and D （P 〈0.005）. The number of apoptotic neurons kept increasing in the ICR mice under CIH condition, and reached the peak in the group D, but there was no significant difference between groups B and C, between groups B and D, and between groups C and D. Nip3 positive neurons in each square millimeter in the cortex of the frontal lobe in each group were calculated by median or Ri as follows： group A （2, 5.5）, group B （117, 13）, group C （227, 26.2）, and group D（479, 21.4）. There were significant differences among the four groups （P=0.000）. The statistical test was performed between the control group and each CIH group respectively： groups A and B （P 〉0.05）; groups A and C （P〈0.005）; and groups A and D （P 〈0.005）. There was no significant difference between groups B and C, groups B and D, and groups C and D. The expression of Nip3 was closely correlated with neuron apoptosis in the brain （P 〈0.05）. The expression of β-amyloid protein in the brain of mice was negative in all CIH groups and the control group. Ultrastructure observation showed karyopyknosis of nucleus, swelling of chondriosomes, deposit of lipofuscins and degeneration of neural sheath in all CIH groups but not in the control group. Conclusion The results of this study indicate that CIH could up-regulate the expression of Nip3, and result in neuron apoptosis and ultrastructural changes in neurons of the frontal cortex.
文摘In Arabidopsis, the nodulin 26-like intrinsic protein （NIP） subfamily of aquaporin proteins consists of nine members, five of which （NIP1;1, NIP1;2, NIP5;1, NIP6;1, and NIP7;1） were previously identified to be perme- able to arsenite. However, the roles of NIPs in the root-to-shoot translocation of arsenite in plants remain poorly understood. In this study, using reverse genetic strategies, Arabidopsis NIP3;1 was identified to play an important role in both the arsenic uptake and root-to-shoot distribution under arsenite stress condi- tions. The nip3;1 loss-of-function mutants displayed obvious improvements in arsenite tolerance for aboveground growth and accumulated less arsenic in shoots than those of the wild-type plants, whereas the nip3;1 nip1;1 double mutant showed strong arsenite tolerance and improved growth of both roots and shoots under arsenite stress conditions. A promoter-β-glucuronidase analysis revealed that NIP3; 1 was ex- pressed almost exclusively in roots （with the exception of the root tips）, and heterologous expression in the yeast Saccharomyces cerevisiae demonstrated that NIP3;1 was able to mediate arsenite transport. Taken together, our results suggest that NIP3;1 is involved in arsenite uptake and root-to-shoot translocation in Arabidopsis, probably as a passive and bidirectional arsenite transporter.
基金This work was supported by the National Natural Science Foundation of China(81622005)Beijing Natural Science Foundation(7172213).
文摘Clinical practice has shown that Parkin is the major causative gene found in an autosomal recessive juvenile parkin-sonism(AR-JP)via Parkin mutations and that the Parkin protein is the core expression product of the Parkin gene,which itself belongs to an E3 ubiquitin ligase.Since the discovery of the Parkin gene in the late 1990s,researchers in many countries have begun extensive research on this gene and found that in addition to AR-JP,the Parkin gene is associated with many diseases,including type 2 diabetes,leprosy,Alzheimer’s,autism,and cancer.Recent studies have found that the loss or dysfunction of Parkin has a certain relationship with tumorigenesis.In general,the Parkin gene,a well-established tumor suppressor,is deficient and mutated in a variety of malignancies.Parkin overexpres-sion inhibits tumor cell growth and promotes apoptosis.However,the functions of Parkin in tumorigenesis and its regulatory mechanisms are still not fully understood.This article describes the structure,functions,and post-transla-tional modifications of Parkin,and summarizes the recent advances in the tumor suppressive function of Parkin and its underlying mechanisms.
