Hydrogen sulphide (H2S), better known to some as the `rotten-egg gas' due to its characteristic pungent odor, is generally thought of as a noxious and toxic gas. Recently though, it was discovered that H2S is naturally produced in animal cells, that it exists in micromolar amounts in the blood and brain of mammals, and that it plays numerous important physiological roles such as acting as a signalling molecule, neuromodulator and regulator of cardiovascular status. Additionally, other studies have reported the intriguing finding that exposure of mammals and/or their tissues to a low dose of H2S actually improves the capacity of the animal or tissue to survive otherwise lethal conditions. However, exactly how H2S exerts these physiological effects remains unknown.
Dana Miller and Mark Roth of the Fred Hutchinson Cancer Research Center in Seattle, Washington were interested in elucidating the molecular mechanisms underlying the beneficial physiological effects of H2S exposure. Ingeniously, the team recognized that they should approach this problem by utilizing the nematode Caenorhabditis elegans as their study species. The genome of C. elegans is completely sequenced and there exist numerous, readily available mutant strains (i.e. strains that have been genetically engineered to have specific genes missing or `knocked-out'). Thus,the team reasoned that by comparing the physiological responses of wild-type(i.e. those with all their genes) and various knock-out strains of nematodes to H2S exposure, they should be able to determine which essential molecular pathways are associated with the beneficial effects of H2S.
However, before searching for the molecular mechanisms, the team had to first determine whether and how H2S exposure is beneficial to nematodes. To accomplish this, the team grew nematodes in atmospheres of room air (the control group) or in the presence of a low concentration of H2S and compared various indices of the nematodes' health, their lifespan and tolerance to high temperature. The team discovered that nematodes grown in H2S were as healthy as the control animals, but that they lived 70% longer and could survive 8 times longer at the stressful high temperature of 35°C.
Armed with this knowledge, the team set out to discover whether the benefits of H2S exposure were linked to any of the known molecular pathways in C. elegans responsible for influencing lifespan. Interestingly, the team found that mutant nematode strains grown in H2S but lacking genes specific to the insulin signalling pathway,mitochondrial dysfunction or caloric dysfunction, were still long lived and thermotolerant, thus excluding the possibility that these molecular pathways are associated with the beneficial effects of H2S. In contrast, the team discovered that nematodes lacking the gene for sir-2.1, an important stress-induced enzyme capable of prolonging life, had the same lifespan and thermotolerance of normal nematodes, despite being grown in H2S.
The team argues that this finding suggests that one cellular activity of H2S is to increase the activity of sir-2.1, which subsequently leads to increased lifespan and thermotolerance, and wonder whether this mechanism is conserved in vertebrates. Only future studies will tell!
