Chemical probe confirms that body makes its own H2S to benefit health

Jun 18, 2013
Chemical probe confirms that body makes its own rotten egg gas, H2S, to benefit health
A still image of live human cells shows them generating hydrogen sulfide, H2S, after being treated with a protein that stimulates blood vessel formation. Researchers developed a new fluorescent chemical probe that makes it possible for scientists to observe cells as they generate H2S. Credit: SMU

(Phys.org) —A new study confirms directly what scientists previously knew only indirectly: The poisonous "rotten egg" gas hydrogen sulfide is generated by our body's growing cells. Hydrogen sulfide, or H2S, is normally toxic, but in small amounts it plays a role in cardiovascular health.

In the new study, chemists developed a chemical probe that reacts and lights up when live generate hydrogen sulfide, says chemist Alexander R. Lippert, Southern Methodist University, Dallas. The discovery allows researchers to observe the process through a microscope.

The researchers captured on video the successful at work, said Lippert, an assistant professor in SMU's Department of Chemistry.

"We made a that, when it reacts with hydrogen sulfide, forms a fluorescent compound that can be visualized using ," Lippert said. "This is the first time that endogenously generated hydrogen sulfide has been directly visualized in a living system. This confirms a lot of hypotheses that scientists have, but no one had the tools to directly detect it in real time."

is one of several small gaseous molecules increasingly recognized as key signaling molecules in the body. For example, H2S helps reduce . Scientists discovered in the past decade that cells in the human body generate small quantities of H2S molecules, which in turn deliver information to proteins. The proteins act on the information to perform critical functions in the body.

Previously, scientists couldn't observe H2S being generated in live cells. As a result, researchers faced challenges when studying hydrogen sulfide in living systems, Lippert said. The now provides a tool to view directly how and when is generated, he said. Lippert and study co-author chemist Vivian S. Lin made the discovery.

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"Having the tools to do this in living systems is going to open up a lot of possibilities and experiments for scientists," Lippert said. "As a tool, this will allow researchers to ask questions that weren't possible before."

Lippert's real-time video features live , taken from the lining of blood vessels and treated with the and with a protein known to promote cell growth. Once the cells start generating H2S, they behave like squiggly fluorescent green worms. Lippert discusses the discovery in a video at http://bit.ly/15ghBDs, which includes the video capture of H2S being generated.

The researchers' scientific article, "Cell-trappable fluorescent probes for endogenous signaling and imaging H2O2 -dependent H2S production," was published online in the Proceedings of the National Academy of Sciences.

Lippert and Lin authored the research with Christopher J. Chang, principal investigator. Lin is a PhD candidate at the University of California at Berkeley. Chang is with the Howard Hughes Medical Institute, University of California at Berkeley. Lippert and Lin carried out the research in Chang's UC Berkeley laboratory.

Discovery can help scientists attack diseases such as cancer

H2S—along with nitric oxide, carbon monoxide and others in this emerging class of gaseous signaling molecules—assists the body's large proteins.

Large proteins do much of the functional work in the body, such as digesting the food we eat and harnessing the energy in the oxygen we breathe. Their size, however, forces them to move slowly inside the cell. In contrast, H2S and other small gaseous molecules diffuse quickly and easily across cellular membranes, enabling them to travel much faster and rapidly deliver information that mediates critical functions, such as blood pressure regulation, Lippert said.

For their experiments, Lippert and Lin placed living endothelial cells cultured from the internal lining of a blood vessel into a petri dish under a microscope.

Lippert and Lin then added a chemical solution containing an azide-functionalized organic molecule that they'd synthesized to act as a . They gave the cells time to absorb the probe, then added a protein solution known to stimulate blood vessel formation. As the cells initiated blood vessel formation, H2S was generated. In reaction, the scientists observed a steady increase in the probe's fluorescence.

"Essentially we're observing the initial events that lead to the building of new blood vessels, a process that's active in babies as they develop, or in women during their menstruation cycles," Lippert said. "We see the cells get really bright as they start moving around and ruffling their membranes. That's the H2S being formed. In the control group, which weren't stimulated with the growth protein, they don't get any brighter and they don't move around."

The discovery provides new insights that can help scientists attack diseases, such as cancer, by starving the nutrient supply to a tumor, Lippert said.

"When tumors grow they need a lot of blood support because they need the nutrients to support their rapid growth," he said. "If you can stop blood vessel formation you could starve the tumor and the tumor will die. So inhibiting formation might be a way to treat cancer using this method."

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More information: www.pnas.org/content/early/201… /10/1302193110.short

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Egleton
not rated yet Jun 18, 2013
I'm guessing that our relationship with H2S goes back a long time.Injecting it into the body causes the cells to go into hibernation, hinting at a survival mechanism for anaerobic bacteria outgassing events on the planet.
nkalanaga
not rated yet Jun 19, 2013
It's probably older than that. Our basic cells are anaerobic, and require the mitochondria to use oxygen. There is considerable evidence that the mitochondria were originally free-living organisms, so the ancestors of our cells, before the merger, would have been anaerobic life forms, possibly even sulfur eaters.

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