MODIFICATION OF DNA BY REDUCING SUGARS - A POSSIBLE MECHANISM FOR NUCLEIC-ACID AGING AND AGE-RELATED DYSFUNCTION IN GENE-EXPRESSION
MODIFICATION OF DNA BY REDUCING SUGARS - A POSSIBLE MECHANISM FOR NUCLEIC-ACID AGING AND AGE-RELATED DYSFUNCTION IN GENE-EXPRESSION
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DOI：
10.1073/pnas.81.1.105
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发表时间：
1984-01-01
期刊：
影响因子：
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通讯作者：
CERAMI, A
中科院分区：
文献类型：
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作者：
BUCALA, R;MODEL, P;CERAMI, A
还原糖与蛋白质氨基发生非酶反应，启动一个称为非酶布朗宁的过程。长寿命蛋白质，如胶原蛋白和透镜晶体蛋白，在体内积累了足够的修饰，使它们获得许多老化蛋白质的化学特性。核酸也可以通过糖进行非酶修饰。DNA或核苷酸与G-6-P孵育产生的光谱变化类似于非酶促布朗宁蛋白质的光谱变化。通过测量与葡萄糖和G-6-P孵育后病毒DNA的转染效率来验证化学修饰的发生。发生转染潜力的损失，其是相对于时间和糖浓度的第一顺序。G-6-P的失活率是葡萄糖的25倍;与150 mM G-6-P孵育8天使转染降低4个数量级。G-6-P也以时间和浓度依赖性方式产生链断裂。葡萄糖、G-6-P和可能的其他糖可以与DNA反应，产生显著的结构和生物学改变。由于核酸是休眠细胞中的长寿分子，这些额外产物的积累可能是衰老生物体遗传活力下降的机制。
Reducing sugars react nonenzymatically with protein amino groups to initiate a process called nonenzymatic browning. Long-lived proteins, such as collagen and the lens crystallins, accumulate sufficient modification in vivo that they acquire many of the chemical properties characteristic of aged proteins. Nucleic acids also can undergo nonenzymatic modification by sugars. Incubation of DNA or nucleotides with G-6-P produces spectral changes similar to those described for nonenzymatic browning proteins. The occurrence of chemical modification was verified by measuring the transfection efficiency of viral DNA after incubation with glucose and G-6-P. A loss of transfection potential occurred that was 1st order with respect to time and sugar concentration. The rate of inactivation by G-6-P was 25 times that of glucose; 8 days of incubation with 150 mM G-6-P decreased transfection by 4 orders of magnitude. G-6-P also produced strand scission in a time- and concentration-dependent manner. Glucose, G-6-P, and possibly other sugars can react with DNA to produce significant structural and biological alterations. Since nucleic acids are long-lived molecules in the resting cell, the accumulation of these addition products might be a mechanism for the decresed genetic viability characteristic of the aged organism.