Pluripotent protective effects of carnosine, a naturally occurring dipeptide
Pluripotent protective effects of carnosine, a naturally occurring dipeptide
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DOI：
10.1111/j.1749-6632.1998.tb09890.x
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发表时间：
1998-01-01
期刊：
影响因子：
--
通讯作者：
Abbott, NJ
中科院分区：
文献类型：
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作者：
Hipkiss, AR;Preston, JE;Abbott, NJ
肌肽是一种天然存在的二肽（β-丙氨酰-L-组氨酸），存在于脑、神经支配组织和透镜中，人体内浓度高达20 mM。1994年，研究表明肌肽可以延缓培养的人成纤维细胞的衰老。有证据表明，肌肽除了具有抗氧化和清除氧自由基的活性外，还与有害的醛类反应以保护敏感的大分子。肌肽抑制活性醛诱导的蛋白质非酶糖基化和交联（醛糖和酮糖，某些丙糖糖酵解中间体和丙二醛（MDA），一种脂质过氧化产物）。此外，我们发现肌肽抑制MDA诱导的蛋白质相关的高级糖基化终产物（AGEs）的形成和乙醛和甲醛诱导的DNA-蛋白质交联的形成。在细胞水平上，20 mM肌肽保护培养的人成纤维细胞和淋巴细胞、CHO细胞和培养的大鼠脑内皮细胞免受甲醛、乙醛和MDA以及由赖氨酸/脱氧核糖混合物形成的AGEs的毒性作用。有趣的是，肌肽保护培养的大鼠脑内皮细胞免受淀粉样肽的毒性。我们建议，肌肽（这是非常无毒）或相关结构应探讨可能的干预病理，涉及有害的醛类，例如，继发性糖尿病并发症，炎症现象，酒精性肝病，并可能阿尔茨海默氏病。
Carnosine is a naturally occurring dipeptide (beta-alanyl-L-histidine) found in brain, innervated tissues, and the lens at concentrations up to 20 mM in humans. In 1994 it was shown that carnosine could delay senescence of cultured human fibroblasts, Evidence will be presented to suggest that carnosine, in addition to antioxidant and oxygen free-radical scavenging activities, also reacts with deleterious aldehydes to protect susceptible macromolecules, Our studies show that, in vitro, carnosine inhibits nonenzymic glycosylation and cross-linking of proteins induced by reactive aldehydes (aldose and ketose sugars, certain triose glycolytic intermediates and malondialdehyde (MDA), a lipid peroxidation product). Additionally we show that carnosine inhibits formation of MDA-induced protein-associated advanced glycosylation end products (AGEs) and formation of DNA-protein cross-links induced by acetaldehyde and formaldehyde. At the cellular level 20 mM carnosine protected cultured human fibroblasts and lymphocytes, CHO cells, and cultured rat brain endothelial cells against the toxic effects of formaldehyde, acetaldehyde and MDA, and AGEs formed by a lysine/deoxyribose mixture. Interestingly, carnosine protected cultured rat brain endothelial cells against amyloid peptide toxicity. We propose that carnosine (which is remarkably nontoxic) or related structures should be explored for possible intervention in pathologies that involve deleterious aldehydes, for example, secondary diabetic complications, inflammatory phenomena, alcoholic liver disease, and possibly Alzheimer's disease.