A Ratiometric Two-Photon Fluorescent Probe Reveals Reduction in Mitochondrial H2S Production in Parkinson's Disease Gene Knockout Astrocytes

被引:389
作者
Bae, Sung Keun [1 ]
Heo, Cheol Ho [1 ]
Choi, Dong Joo [2 ]
Sen, Debabrata [1 ]
Joe, Eun-Hye [2 ]
Cho, Bong Rae [3 ]
Kim, Hwan Myung [1 ]
机构
[1] Ajou Univ, Div Energy Syst Res, Suwon 443749, South Korea
[2] Ajou Univ, Sch Med, Dept Pharmacol, Neurosci Grad Program, Suwon 443721, South Korea
[3] Korea Univ, Dept Chem, Seoul 136701, South Korea
基金
新加坡国家研究基金会;
关键词
HYDROGEN-SULFIDE; INFLAMMATORY RESPONSES; DJ-1; GLUTATHIONE; DYSFUNCTION; TISSUE;
D O I
10.1021/ja404004v
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Hydrogen sulfide (H2S) is a multifunctional signaling molecule that exerts neuroprotective effects in oxidative stress. In this article, we report a mitochondria localized two photon probe, SHS-M2, that can be excited by 750 nm femtosecond pulses and employed for ratiometric detection of H2S in live astrocytes and living brain slices using two-photon microscopy (TPM). SHS-M2 shows bright two-photon-excited fluorescence and a marked change in emission color from blue to yellow in response to H2S, low cytotoxicity, easy loading, and minimum interference from other biologically relevant species including reactive sulfur, oxygen, and nitrogen species, thereby allowing quantitative analysis of H2S levels. Molecular TPM imaging with SHS-M2 in astrocytes revealed that there is a correlation between the ratiometric analysis and expression levels of cystathionine beta-synthase (CBS), the major enzyme that catalyzes H2S production. In studies involving DJ-1, a Parkinson's disease (PD) gene, attenuated H2S production in comparison with wild-type controls was observed in DJ-1-knockout astrocytes and brain slices, where CBS expression was decreased. These findings demonstrate that reduced H2S levels in astrocytes may contribute to the development of PD and that SHS-M2 may be useful as a marker to detect a risk of neurodegenerative diseases, including PD.
引用
收藏
页码:9915 / 9923
页数:9
相关论文
共 55 条
[1]  
Abe K, 1996, J NEUROSCI, V16, P1066
[2]  
[Anonymous], 2005, INVITROGEN MOL PROBE
[3]   Parkinson's disease-associated DJ-1 modulates innate immunity signaling in Caenorhabditis elegans [J].
Castro, Elena M. Cornejo ;
Waak, Jens ;
Weber, Stephanie S. ;
Fiesel, Fabienne C. ;
Oberhettinger, Philipp ;
Schuetz, Monika ;
Autenrieth, Ingo B. ;
Springer, Wolfdieter ;
Kahle, Philipp J. .
JOURNAL OF NEURAL TRANSMISSION, 2010, 117 (05) :599-604
[4]   Age-dependent motor deficits and dopaminergic dysfunction in DJ-1 null mice [J].
Chen, LN ;
Cagniard, B ;
Mathews, T ;
Jones, S ;
Koh, HC ;
Ding, YM ;
Carvey, PM ;
Ling, ZD ;
Kang, UJ ;
Zhuang, XX .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (22) :21418-21426
[5]   Reaction-Based Genetically Encoded Fluorescent Hydrogen Sulfide Sensors [J].
Chen, Si ;
Chen, Zhi-jie ;
Ren, Wei ;
Ai, Hui-wang .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2012, 134 (23) :9589-9592
[6]   A Ratiometric Fluorescent Probe for Rapid Detection of Hydrogen Sulfide in Mitochondria [J].
Chen, Yuncong ;
Zhu, Chengcheng ;
Yang, Zhenghao ;
Chen, Junjie ;
He, Yafeng ;
Jiao, Yang ;
He, Weijiang ;
Qiu, Lin ;
Cen, Jiajie ;
Guo, Zijian .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2013, 52 (06) :1688-1691
[7]   An Integrated Imaging Approach to the Study of Oxidative Stress Generation by Mitochondrial Dysfunction in Living Cells [J].
Cheng, Wan-Yun ;
Tong, Haiyan ;
Miller, Evan W. ;
Chang, Christopher J. ;
Remington, James ;
Zucker, Robert M. ;
Bromberg, Philip A. ;
Samet, James M. ;
Hofer, Thomas P. J. .
ENVIRONMENTAL HEALTH PERSPECTIVES, 2010, 118 (07) :902-908
[8]  
DEMAS JN, 1971, J PHYS CHEM-US, V75, P991, DOI 10.1021/j100678a001
[9]   Two-photon excited fluorescent probes for calcium based on internal charge transfer [J].
Dong, Xiaohu ;
Yang, Yiyao ;
Sun, Jian ;
Liu, Zhihong ;
Liu, Bi-Feng .
CHEMICAL COMMUNICATIONS, 2009, (26) :3883-3885
[10]   RETRACTED: Brain hydrogen sulfide is severely decreased in Alzheimer's disease (Retracted Article) [J].
Eto, K ;
Asada, T ;
Arima, K ;
Makifuchi, T ;
Kimura, H .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2002, 293 (05) :1485-1488