衰老过程中的羰基应激

发布时间：2018-05-18 10:32

本文选题：衰老 + 羰基应激　；参考：《湖南师范大学》2006年博士论文

【摘要】：随着衰老研究的深入,研究者们对衰老的认识经历了由主动衰老→被动衰老,由程序性死亡→随机损伤积累的过程;也正是因为认识论的发展,目前随机性损伤累积的杰出代表——自由基/氧化应激衰老理论已被认为是“第一衰老理论”。而随着研究的深入,需氧参与的自由基氧化和不需氧参与的非酶糖基化,这两大最重要的能量代谢相关生化副反应,都被证实与许多疾病的病理机制以及衰老密切相关,而细察其两者的作用过程,发现它们均产生具有很强生物反应活性的毒性羰基类物质;考虑到毒性羰基类物质本身的特点及其与生物大分子的作用方式,我们进而思考:羰基应激是否是自由基氧化和非酶糖基化造成的衰老相关改变的直接方式呢?值此,产生了本学位论文——衰老过程中的羰基应激。根据论题,本论文的主要从两个方面开展探索:即羰基应激研究和去羰基应激研究。首先,从生化水平证实了老年色素形成过程的羰基应激机制。通过引入前表面三维荧光技术,从根本上解决了老年色素检测的技术问题,利用该方法得到了老年色素的全波段荧光光谱信息,从而以清晰的数据彻底澄清了困扰老年色素研究长达几十年之久的颜色之争(蓝色和黄褐色);根据前表面三维荧光数据,我们进一步从简单和复杂的体系综合证实了:随着老年色素的“成熟”过程,老年色素的峰出现了红移;并且随着羰基应激的加剧,老年色素的形成也加剧,随着羰基应激的抑制,老年色素的形成也得到了抑制。这些充分的实验事实表明:羰基应激(特别是羰-氨交联)是老年色素形成的核心生化机制之一。其次,从细胞水平发现了丙二醛(malondialdehyde,MDA)直
[Abstract]:With the deepening of aging research, researchers' understanding of aging has gone through the process of active senescence and passive senescence, and the accumulation of random damage caused by programmed death, which is also due to the development of epistemology. At present, the theory of free radical / oxidative stress senescence has been regarded as the "first aging theory", which is an outstanding representative of random damage accumulation. With the development of research, aerobic free radical oxidation and non-aerobic non-enzymatic glycosylation, the two most important biochemical side effects related to energy metabolism, have been proved to be closely related to the pathological mechanism of many diseases and aging. After careful examination of the processes of their action, it was found that both of them produced toxic carbonyl substances with strong biological activity, considering the characteristics of the toxic carbonyl substances themselves and the way in which they acted with biological macromolecules, We went on to wonder whether carbonyl stress was a direct way of changing senescence related to free radical oxidation and non-enzymatic glycosylation. Therefore, the carbonyl stress in the process of senescence is produced in this dissertation. According to the topic, this thesis mainly explores two aspects: carbonyl stress and decarbonyl stress. Firstly, the mechanism of carbonyl stress in the formation of aged pigments was confirmed at the biochemical level. By introducing the three dimensional fluorescence technique of the front surface, the technical problem of the detection of the aged pigment is solved fundamentally, and the full-band fluorescence spectrum information of the aged pigment is obtained by using this method. Thus, with clear data, the color dispute (blue and yellowish brown) that has plagued the study of geriatric pigments for decades (blue and yellowish brown) has been completely clarified; according to the three dimensional fluorescence data on the front surface, We further demonstrated from simple and complex systems that the peak of senile pigments shifted red with the "maturation" of pigments, and that the formation of geriatric pigments increased with the increase of carbonyl stress. With the inhibition of carbonyl stress, the formation of senile pigments was also inhibited. These sufficient experimental facts indicate that carbonyl stress (especially carbonyl-ammonia crosslinking) is one of the core biochemical mechanisms for the formation of aged pigments. Secondly, malondialdehyde (malondialdehyde) was found at cell level.
【学位授予单位】：湖南师范大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R33

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