Beruflich Dokumente
Kultur Dokumente
Powell Bagdon, Nelmi O. Devarie-Baez, Chung-Min Park, Yu Zhao, Bo Peng, Ming Xian* Department of Chemistry, Washington State University, Pullman , WA 99164
Background
It has long been known that hydrogen sulfide gas (H2S) is harmful and sometimes fatal at high concentrations, but recent studies have suggested that it is also plays an important role in cell biology and signaling. Mammals are able to produce H2S in a controllable manner. This production is attributed to several sources: three enzymes (cystathionine--synthetase, cystathionine-lysase and 3-mercaptopyruvate sulfurtransferase), FeS clusters and bound sulfane sulfur. In biological systems H2S has been attributed to a number of important tasks including neuromodulation, vasodilation, antiagrregatory activity against platelets, anti-inflammatory processes, the angiogenesis of wound healing [1-3]. Currently the most commonly used H2S donors are solutions of NaSH, Na2S and CaS. These donors are none-controllable and do not accurately emulate biological levels of H2S. In contrast to these inorganic donors, organic donors have been proven to produce H2S controllably and at concentrations much closer to those observed in cells. Organic donors can be triggered to release H2S upon exposure to a number of external stimuli including light, pH, and through activation by biothiol [4], but at this time only a few such donors, shown below, have been created and as such there is a large need for the development of new, controllable donors with varied activation mechanisms. Here the development of two such organic, controllable H2S donors is presented.
Scheme
A B
7b
Figure 5. Fluorescent image of cells incubated in donor 1d and fluorescent H2S probe WSP-1 [6] before and after irradiation with UV light.
w/o light
w/ light
Figure 6. Fluorescent image of cells incubated in donor 2a and WSP-1. A: 0 M donor B: 100 M. C: 200 M.
Conclusion
Both donor templates controllably release H2S in aqueous solution. Phosphorodithiolate based donors 2a-c were found to be as effective as commonly used GYY4137 at controllably releasing H2S. Light activated donors 1a-f were found to controllably release H2S upon irradiation with UV light. It is expected that this new class of donor can allow for both spatial and temporal control of H2S release, and be used in the study real time of H2S activities.
Acknowledgement
We would like to thank the Washington State University College of Arts and Sciences, American Chemical Society-Teva USA Scholar Grant and the NIH (R01GM088226) for support of this research.
H2S (uM)
References
Time (min)
GYY4137
1a
2b
2c
Figure 3. The release profiles of donors 2a-c compared with the known donor GYY4137 in 1:1 ACN/PBS (pH=7.4) measured with the selective H2S fluorescent probe Dz-N3 [5].
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Figure 2. The release profiles of donors 1a-f after irradiation with UV light (=365nm).
Figure 4. H9c2 cells viability after oxidative injury by H2O2 in the presence of donors 2a, 2b, GYY4137 and NaSH .