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机构地区:[1]湖南师范大学生命科学学院衰老生化研究室,中国湖南长沙410081
出 处:《生命科学研究》2003年第2期116-122,共7页Life Science Research
基 金:国家自然科学基金资助项目(30070874)
摘 要:羰基应激(如:蛋白交联、醛 氨反应)是自由基和美拉德反应的共同结果,也是衰老的重要过程.尽管生物体本身有羰基降解酶和其它羰基解毒系统,然而,即使在健康组织中也还是有大量的有毒羰基化合物存在,特别是不饱和醛酮,如:马龙二醛、4 羟基壬烯醛等.这些不饱和醛酮在生理pH条件下就能与几乎所有的重要生物分子(如:蛋白质、核苷酸等)自发反应,导致一系列与衰老相关的变异.体内的不饱和醛酮还是谷胱甘肽下降、细胞膜损坏、酶功能抑制、免疫混乱、遗传变异、细胞复制受阻等病理变化的主要测定指标和重要原因;同时也是糖基化终产物、老年色素、眼球晶体白内障及胶原组织交联等老化现象的前体物质.因此,不饱和醛酮的毒害可能是机体衰老的核心过程.Carbonyl stress (e.g.,crosslinking and aldehydeamino reactions) of biomolcules,a common consequence of free radical/Maillard reactions,is an important process of biological aging.In spite of detoxification of carbonyls by a family of carbonyl dehydrogenases and other biomolcules (e.g.,glutathione),even healthy organism contain micromolar amounts of carbonyls,particularly carbonyls with di and multifunctional groups (DMCs),e.g.,malondialdehyde,4hydroxylnonenal,which are all biologically toxic.DMCs react readily at physiological pH with almost all important biomolcules,e.g.,proteins,lipids,carbohydrates,nucleic acids,causing a variety of biological alterations,e.g.,protein crosslinking,which affect most (if not all) aspects of body organization and function.DMCs,derived from both free radical and Maillard reactions,are biomarkers that are correlated with glutathione depletion,membrane destruction,enzyme inhibition,immune disturbances,mutations,inhibition of cell replication,etc.DMCs are also known precursors of advanced glycation end products,age pigments (lipofuscin) in postmitotic cells,lens cataracts,and collagen crosslinking.DMCs stress of biomolcules,therefore,is considered to be a central process related to organismic aging.
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