In this confocal microscopy image, live human umbilical cord cells glow green as Chang’s probe detects H2S inside them.
Infamous for being the source of rotten-egg stench, hydrogen sulfide (H2S) has a rather complicated place in biology. The human body makes it. It is both poisonous—linked to diseases such as type 1 diabetes—and beneficial to activities such as immune signaling. Researchers would like to know more about how H2S is made and how it exerts its effects, but they have lacked tools to noninvasively monitor the compound in living beings.
Chang’s lab first reported fluorescent probes for H2S two years ago. The probes selectively light up in the presence of H2S because they contain an aryl azide group that only H2S can reduce to a fluorescent product. Those probes, however, weren’t sensitive enough to detect biologically relevant levels of H2S.
To fix that, Chang lab members Vivian S. Lin and Alexander R. Lippert made two improvements. They increased the probes’ sensitivity by adding a second aryl azide group. They also added two acetoxymethyl ester groups, which are lipophilic and help the probe enter cells. Once inside, the groups get cleaved by esterases, rendering the probe incapable of leaving. The probes accumulate inside cells, further boosting sensitivity.
With the improved probes, the team followed H2S production in cells from umbilical cords. They found evidence to back a hunch held by members of several other labs—H2S production depends on a signal from hydrogen peroxide. That’s a fascinating relationship, Chang says, because H2O2 is an oxidant and H2S is a reductant. The biochemistry linking those chemical opposites is far from clear, so “it’s going to be exciting to learn more about that cross talk,” he says.
“This work presages many exciting new directions in both redox and chemical biology,” says Kate Carroll, who maps redox signaling at Scripps Research Institute Florida. “A central goal for future studies will be to define the molecular targets of H2O2, H2S, and other redox-based signaling molecules.”