Carnosine: can understanding its actions on energy metabolism and protein homeostasis inform its therapeutic potential?
Carnosine: can understanding its actions on energy metabolism and protein homeostasis inform its therapeutic potential?
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DOI：
10.1186/1752-153x-7-38
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发表时间：
2013-02-25
影响因子：
--
通讯作者：
Bill RM
中科院分区：
文献类型：
--
作者：
Hipkiss AR;Cartwright SP;Bromley C;Gross SR;Bill RM
二肽肌肽（β-丙氨酰-L-组氨酸）对细胞活性具有相反但有益的作用。它延缓细胞衰老并使培养的衰老哺乳动物细胞恢复活力。然而，它也抑制培养的肿瘤细胞的生长。基于在几种生物体中的研究，我们推测肌肽通过影响能量代谢和/或蛋白质稳态（蛋白质稳态）来发挥这些明显相反的作用。对能量代谢的具体影响包括二肽对细胞ATP浓度的影响。肌肽减少改变的蛋白质（通常是甲基乙二醛的加合物）的形成和增强异常多肽的蛋白水解的能力表明其对蛋白质稳态的影响。此外，这些双重作用可能为肌肽在治疗或预防能量代谢或蛋白质稳态受损的各种年龄相关病症中的使用提供了理论基础。这些疾病包括癌症、阿尔茨海默病、帕金森病和2型糖尿病的并发症（肾病、白内障、中风和疼痛），这些疾病都可能受益于肌肽对人体细胞作用方式的知识。
The dipeptide carnosine (β-alanyl-L-histidine) has contrasting but beneficial effects on cellular activity. It delays cellular senescence and rejuvenates cultured senescent mammalian cells. However, it also inhibits the growth of cultured tumour cells. Based on studies in several organisms, we speculate that carnosine exerts these apparently opposing actions by affecting energy metabolism and/or protein homeostasis (proteostasis). Specific effects on energy metabolism include the dipeptide’s influence on cellular ATP concentrations. Carnosine’s ability to reduce the formation of altered proteins (typically adducts of methylglyoxal) and enhance proteolysis of aberrant polypeptides is indicative of its influence on proteostasis. Furthermore these dual actions might provide a rationale for the use of carnosine in the treatment or prevention of diverse age-related conditions where energy metabolism or proteostasis are compromised. These include cancer, Alzheimer's disease, Parkinson's disease and the complications of type-2 diabetes (nephropathy, cataracts, stroke and pain), which might all benefit from knowledge of carnosine’s mode of action on human cells.