Alzheimer disease has been defined as Type 3 Diabetes due to their shared metabolic profiles. Like our previously research, results of Alzheimer’s disease and other neurodegenerative diseases, systematic analysis of ...Alzheimer disease has been defined as Type 3 Diabetes due to their shared metabolic profiles. Like our previously research, results of Alzheimer’s disease and other neurodegenerative diseases, systematic analysis of diabetes- and glucose metabolism-related proteins also provides help in the treatment of Alzheimer’s patients. Some interesting results indicate that diabetes-related proteins (DRPs) are rich in Lys and the content of Trp can distinguish between type 1 and type 2 diabetes mellitus in particular, while glucose metabolism-related proteins (GMRPs) possess Leurich and Trp-poor character. Moreover, the usage biases of codons depend on GC contents to a great extent, in concord with all codons of the highly expressed genes with the terminal of C/G. Especially, the deficit of CpG dinucleotides is largely attributed to the hypermutability of methylated CpGs to UpGs by the mutational pressure. Besides a common node insulin receptor, there are some similar node proteins, such as glucose transporter member, protein tyrosine phosphatase, and adipose metabolism signal protein. The sharing proteins involve glucagon, amylin, insulin, PPARγ, angiopoietin, PC-1/ENPP1, and adiponectin mediated signal pathway. Meanwhile, the gene sequences of node proteins contained the binding sites of 37 transcription factors divide into four kinds of superclasses. Additionally, BAD complex can integrate pathways of glucose metabolism and apoptosis by BH3 domain of BAD directly interacting with GK as well as GK binding with the consensus motif [G]-[1]-[K]-[2]-[S/T] or [L/M]-[R/K]-[2]-[T] of PP1 or WAVE1. This facilitates the therapies for diabetes mellitus as well as Alzheimer’s disease.展开更多
Background: Particulate matter(PM), which has adverse effects on citizen health, is a major air pollutant in Beijing city. PM_(2.5) is an indicator of PM in urban areas and can cause serious damage to human health. Ma...Background: Particulate matter(PM), which has adverse effects on citizen health, is a major air pollutant in Beijing city. PM_(2.5) is an indicator of PM in urban areas and can cause serious damage to human health. Many epidemiological studies have shown that nuclear factor-kappa B(NF-κB) is involved in PM_(2.5)-induced cell injury, but the exact mechanisms are not well understood.Methods: The cytotoxic effects of PM_(2.5) at 25–1600μg/ml for 24 h were determined by MTT assay in Chinese hamster ovary cells(CHO) cells. Flow cytometry was used to determine the apoptosis rate induced by PM_(2.5). The destabilized enhanced green fluorescent protein(d2 EGFP) green fluorescent protein reporter system was used to determine the NF-κB activity induced by PM_(2.5). The expression of pro-apoptotic Bcl-2-associated death promoter(BAD) proteins induced by PM_(2.5) was determined by Western blotting to explore the relationship between PM_(2.5) and the NF-κB signaling pathway and to determine the toxicological mechanisms of PM_(2.5).Results: PM_(2.5) collected in Beijing urban districts induces cytotoxic effects in CHO cells according to MTT assay with 72.28% cell viability rates even at 200μg/ml PM_(2.5) and flow cytometry assays with 26.97% apoptosis rates at 200μg/ml PM_(2.5). PM_(2.5) increases the activation levels of NF-κB, which have maintained for 24 h. 200μg/ml PM_(2.5) cause activation of NF-κB after exposure for 4 h, the activation peak appears after 13.5 h with a peak value of 25.41%. The average percentage of NF-κB activation in whole 24 h is up to 12.90% by 200μg/ml PM_(2.5). In addition, PM_(2.5) decreases the expression level of the pro-apoptotic protein BAD in a concentration-dependent manner.Conclusion: PM_(2.5) induces NF-κB activation, which persists for 24 h. The expression of pro-apoptotic protein BAD decreased with increased concentrations of PM_(2.5). These findings suggest that PM_(2.5) plays a major role in apoptosis by activating the NF-κB signaling pathway and reducing BAD protein expression.展开更多
文摘Alzheimer disease has been defined as Type 3 Diabetes due to their shared metabolic profiles. Like our previously research, results of Alzheimer’s disease and other neurodegenerative diseases, systematic analysis of diabetes- and glucose metabolism-related proteins also provides help in the treatment of Alzheimer’s patients. Some interesting results indicate that diabetes-related proteins (DRPs) are rich in Lys and the content of Trp can distinguish between type 1 and type 2 diabetes mellitus in particular, while glucose metabolism-related proteins (GMRPs) possess Leurich and Trp-poor character. Moreover, the usage biases of codons depend on GC contents to a great extent, in concord with all codons of the highly expressed genes with the terminal of C/G. Especially, the deficit of CpG dinucleotides is largely attributed to the hypermutability of methylated CpGs to UpGs by the mutational pressure. Besides a common node insulin receptor, there are some similar node proteins, such as glucose transporter member, protein tyrosine phosphatase, and adipose metabolism signal protein. The sharing proteins involve glucagon, amylin, insulin, PPARγ, angiopoietin, PC-1/ENPP1, and adiponectin mediated signal pathway. Meanwhile, the gene sequences of node proteins contained the binding sites of 37 transcription factors divide into four kinds of superclasses. Additionally, BAD complex can integrate pathways of glucose metabolism and apoptosis by BH3 domain of BAD directly interacting with GK as well as GK binding with the consensus motif [G]-[1]-[K]-[2]-[S/T] or [L/M]-[R/K]-[2]-[T] of PP1 or WAVE1. This facilitates the therapies for diabetes mellitus as well as Alzheimer’s disease.
基金the Education Committee of Beijing Science and Technology Plan Key Project(No.KZ201211417041)
文摘Background: Particulate matter(PM), which has adverse effects on citizen health, is a major air pollutant in Beijing city. PM_(2.5) is an indicator of PM in urban areas and can cause serious damage to human health. Many epidemiological studies have shown that nuclear factor-kappa B(NF-κB) is involved in PM_(2.5)-induced cell injury, but the exact mechanisms are not well understood.Methods: The cytotoxic effects of PM_(2.5) at 25–1600μg/ml for 24 h were determined by MTT assay in Chinese hamster ovary cells(CHO) cells. Flow cytometry was used to determine the apoptosis rate induced by PM_(2.5). The destabilized enhanced green fluorescent protein(d2 EGFP) green fluorescent protein reporter system was used to determine the NF-κB activity induced by PM_(2.5). The expression of pro-apoptotic Bcl-2-associated death promoter(BAD) proteins induced by PM_(2.5) was determined by Western blotting to explore the relationship between PM_(2.5) and the NF-κB signaling pathway and to determine the toxicological mechanisms of PM_(2.5).Results: PM_(2.5) collected in Beijing urban districts induces cytotoxic effects in CHO cells according to MTT assay with 72.28% cell viability rates even at 200μg/ml PM_(2.5) and flow cytometry assays with 26.97% apoptosis rates at 200μg/ml PM_(2.5). PM_(2.5) increases the activation levels of NF-κB, which have maintained for 24 h. 200μg/ml PM_(2.5) cause activation of NF-κB after exposure for 4 h, the activation peak appears after 13.5 h with a peak value of 25.41%. The average percentage of NF-κB activation in whole 24 h is up to 12.90% by 200μg/ml PM_(2.5). In addition, PM_(2.5) decreases the expression level of the pro-apoptotic protein BAD in a concentration-dependent manner.Conclusion: PM_(2.5) induces NF-κB activation, which persists for 24 h. The expression of pro-apoptotic protein BAD decreased with increased concentrations of PM_(2.5). These findings suggest that PM_(2.5) plays a major role in apoptosis by activating the NF-κB signaling pathway and reducing BAD protein expression.
