5-Aminolevulinic acid regulates the inflammatory response and alloimmune reaction
5-Aminolevulinic acid regulates the inflammatory response and alloimmune reaction
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DOI：
10.1016/j.intimp.2015.11.034
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发表时间：
2016-08-01
影响因子：
5.6
通讯作者：
Li, Xiao-Kang
中科院分区：
文献类型：
--
作者：
Fujino, Masayuki;Nishio, Yoshiaki;Li, Xiao-Kang
5-氨基乙酰丙酸（5-ALA）是一种天然存在的氨基酸，是血红素和原卟啉IX （PpIX）的前体。外源性给药5-ALA增加肿瘤细胞中PpIX的积累，特别是由于线粒体中5-ALA对血红素的代谢受损。PpIX通过蓝光照射和活性氧和单线态氧的形成而发出红色荧光。因此，使用5-ALA进行光动力诊断（PDD）和光动力治疗（PDT）已经产生了一种新的肿瘤诊断和治疗策略。除了肿瘤治疗领域，5-ALA还涉及炎症性疾病、自身免疫性疾病和移植的治疗，这是因为血红素加氧酶(HO)-1的表达引发了抗炎症和免疫调节特性，血红素加氧酶(HO)-1是一种诱导酶，与柠檬酸亚铁钠（SFC）结合，催化血红素氧化降解为游离铁、胆绿素和一氧化碳（CO）的限速步骤。因为HO-1的抑制剂会消除5-ALA的作用。此外，NF-E2相关因子2 （Nrf2）、丝裂原活化蛋白激酶（MAPK）和血红素也参与HO-1的表达。胆绿素和一氧化碳还具有抗凋亡、抗炎和免疫调节功能。本文综述了5-ALA在炎症性疾病、移植医学和肿瘤治疗中的应用现状。(C) 2015年作者。Elsevier B.V.出版
5-Aminolevulinic acid (5-ALA) is a naturally occurring amino acid and precursor of heme and protoporphyrin IX (PpIX). Exogenously administrated 5-ALA increases the accumulation of PpIX in tumor cells specifically due to the compromised metabolism of 5-ALA to heme in mitochondria. PpIX emits red fluorescence by the irradiation of blue light and the formation of reactive oxygen species and singlet oxygen. Thus, performing a photodynamic diagnosis (PDD) and photodynamic therapy (PDT) using 5-ALA have given rise to a new strategy for tumor diagnosis and therapy. In addition to the field of tumor therapy, 5-ALA has been implicated in the treatment of inflammatory disease, autoimmune disease and transplantation due to the anti-inflammation and immunoregulation properties that are elicited with the expression of heme oxygenase (HO)-1, an inducible enzyme that catalyzes the rate limiting step in the oxidative degradation of heme to free iron, biliverdin and carbon monoxide (CO), in combination with sodium ferrous citrate (SFC), because an inhibitor of HO-1 abolishes the effects of 5-ALA. Furthermore, NF-E2 related factor 2 (Nrf2), mitogen-activated protein kinase (MAPK), and heme are involved in the HO-1 expression. Biliverdin and CO are also known to have anti-apoptotic, anti-inflammatory and immunoregulatory functions. We herein review the current use of 5-ALA in inflammatory diseases, transplantation medicine, and tumor therapy. (C) 2015 The Authors. Published by Elsevier B.V.