Iron prochelator BSIH protects retinal pigment epithelial cells against cell death induced by hydrogen peroxide.
Iron prochelator BSIH protects retinal pigment epithelial cells against cell death induced by hydrogen peroxide.
复制标题
DOI：
10.1016/j.jinorgbio.2008.08.001
复制
发表时间：
2008-12
影响因子：
3.9
通讯作者：
Franz, Katherine J.
中科院分区：
文献类型：
--
作者：
Charkoudian, Louise K.;Dentchev, Tzvete;Lukinova, Nina;Wolkow, Natalie;Dunaief, Joshua L.;Franz, Katherine J.
局部铁稳态的失调涉及几种退行性疾病，包括帕金森氏病、阿尔茨海默氏病和年龄相关性黄斑变性，其中铁介导的氧化应激被假设有助于细胞死亡。在不改变正常金属依赖性过程的情况下抑制有毒铁对标准小分子螯合剂提出了重大挑战。我们先前介绍了BSIH（异烟酸[2-（4，4，5，5-四甲基-[1，3，2]二氧杂硼杂环戊烷-2-基）-亚苄基]-酰肼）前螯合剂，其通过过氧化氢转化为抑制铁催化的羟基自由基产生的SIH（水杨醛异烟酰腙）螯合剂。在这里，我们表明，BSIH保护视网膜色素上皮细胞培养的细胞模型对过氧化氢诱导的细胞死亡。BSIH在细胞培养基中比SIH更稳定，在长期实验中更具保护性。细胞反复暴露于BSIH是无毒的，而SIH和去铁胺在反复暴露后诱导细胞死亡。结合，我们的研究结果表明，BSIH的细胞保护涉及铁螯合，只发生在细胞受到过氧化氢的压力。这些研究结果表明，prochelators歧视有毒铁从健康的铁，是有前途的候选人神经和视网膜保护。
Dysregulation of localized iron homeostasis is implicated in several degenerative diseases, including Parkinson’s, Alzheimer’s, and age-related macular degeneration, wherein iron-mediated oxidative stress is hypothesized to contribute to cell death. Inhibiting toxic iron without altering normal metal-dependent processes presents significant challenges for standard small molecule chelating agents. We previously introduced BSIH (isonicotinic acid [2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzylidene]-hydrazide) prochelators that are converted by hydrogen peroxide into SIH (salicylaldehyde isonicotinoyl hydrazone) chelating agents that inhibit iron-catalyzed hydroxyl radical generation. Here, we show that BSIH protects a cultured cell model for retinal pigment epithelium against cell death induced by hydrogen peroxide. BSIH is more stable than SIH in cell culture medium and is more protective during long-term experiments. Repetitive exposure of cells to BSIH is nontoxic, whereas SIH and desferrioxamine induce cell death after repeated exposure. Combined, our results indicate that cell protection by BSIH involves iron sequestration that occurs only when the cells are stressed by hydrogen peroxide. These findings suggest that prochelators discriminate toxic iron from healthy iron and are promising candidates for neuro- and retinal protection.
登录
查看更多内容
影响因子：
15
作者：
Charkoudian, Louise K.;Pham, David M.;Franz, Katherine J.
通讯作者：
Franz, Katherine J.
影响因子：
3
作者：
Chwiej, Joanna;Adamek, Dariusz;Lankosz, Marek
通讯作者：
Lankosz, Marek
影响因子：
4.4
作者：
Dunaief, Joshua L.
通讯作者：
Dunaief, Joshua L.
影响因子：
5.8
作者：
WALDMEIER, PC;BUCHLE, AM;STEULET, AF
通讯作者：
STEULET, AF
DOI：
10.1073/pnas.94.18.9866
发表时间：
1997-09-02
影响因子：
11.1
作者：
Smith, MA;Harris, PLR;Perry, G
通讯作者：
Perry, G