Aldehyde dehydrogenase 7A1 (ALDH7A1) attenuates reactive aldehyde and oxidative stress induced cytotoxicity.
Aldehyde dehydrogenase 7A1 (ALDH7A1) attenuates reactive aldehyde and oxidative stress induced cytotoxicity.
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DOI：
10.1016/j.cbi.2011.02.016
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发表时间：
2011-05-30
影响因子：
5.1
通讯作者：
Vasiliou, Vasilis
中科院分区：
文献类型：
--
作者：
Brocker, Chad;Cantore, Miriam;Failli, Paola;Vasiliou, Vasilis
哺乳动物醛脱氢酶7A 1（ALDH 7A 1）与植物ALDH 7 B1同源，其保护免受各种形式的胁迫，例如增加的盐度、脱水和用氧化剂或杀虫剂处理。人类ALDH 7A 1的有害突变导致吡哆醇依赖性和亚叶酸反应性癫痫发作。在以前的研究中，我们已经表明，人ALDH 7A 1可能通过生成甜菜碱（一种重要的细胞渗透压调节剂，由甜菜碱醛形成）来保护免受高渗应激。高渗应激与氧化应激和脂质过氧化（LPO）的增加相关。在这项研究中，细胞活力测定显示，线粒体ALDH 7A 1在中国仓鼠卵巢（CHO）细胞中的稳定表达提供了显着的保护，对治疗与LPO衍生的醛己醛和4-羟基-2-壬烯醛（4 HNE）暗示的氧化应激过程中的酶的保护功能。在用增加浓度的过氧化氢（H2 O2）或4 HNE处理的表达线粒体或胞质ALDH 7A 1的CHO细胞中也观察到细胞存活率的显著增加，这为抗氧化活性提供了进一步的证据。体外酶活性测定表明，人ALDH 7A 1对氧化敏感，并且通过将重组蛋白与巯基还原剂β-巯基乙醇（BME）一起孵育可以至少部分恢复效率。我们还表明，与BME再活化后，重组ALDH 7A 1是能够代谢的反应性醛4 HNE。总之，ALDH 7A 1似乎通过多种途径提供细胞保护机制，包括除去有毒的LPO衍生的醛类以及产生渗透剂。
Mammalian aldehyde dehydrogenase 7A1 (ALDH7A1) is homologous to plant ALDH7B1 which protects against various forms of stress such as increased salinity, dehydration and treatment with oxidants or pesticides. Deleterious mutations in human ALDH7A1 are responsible for pyridoxine-dependent and folinic acid-responsive seizures. In previous studies, we have shown that human ALDH7A1 protects against hyperosmotic stress presumably through the generation of betaine, an important cellular osmolyte, formed from betaine aldehyde. Hyperosmotic stress is coupled to an increase in oxidative stress and lipid peroxidation (LPO). In this study, cell viability assays revealed that stable expression of mitochondrial ALDH7A1 in Chinese hamster ovary (CHO) cells provides significant protection against treatment with the LPO-derived aldehydes hexanal and 4-hydroxy-2-nonenal (4HNE) implicating a protective function for the enzyme during oxidative stress. A significant increase in cell survival was also observed in CHO cells expressing either mitochondrial or cytosolic ALDH7A1 treated with increasing concentrations of hydrogen peroxide (H2O2) or 4HNE, providing further evidence for anti-oxidant activity. In vitro enzyme activity assays indicate that human ALDH7A1 is sensitive to oxidation and that efficiency can be at least partially restored by incubating recombinant protein with the thiol reducing agent β-mercaptoethanol (BME). We also show that after reactivation with BME, recombinant ALDH7A1 is capable of metabolizing the reactive aldehyde 4HNE. In conclusion, ALDH7A1 mechanistically appears to provide cells protection through multiple pathways including the removal of toxic LPO-derived aldehydes in addition to osmolyte generation.
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影响因子：
11.2
作者：
Gallagher, Renata C.;Van Hove, Johan L. K.;Jakobs, Cornelis
通讯作者：
Jakobs, Cornelis
影响因子：
5.1
作者：
GUERRERO, FD;JONES, JT;MULLET, JE
通讯作者：
MULLET, JE
影响因子：
4.1
作者：
Doorn, JA;Hurley, TD;Petersen, DR
通讯作者：
Petersen, DR
影响因子：
13.5
作者：
MITCHELL, DY;PETERSEN, DR
通讯作者：
PETERSEN, DR
影响因子：
2.2
作者：
Galasko D;Montine TJ
通讯作者：
Montine TJ