Thursday, January 1, 2015

Hydrogen Sulfide (H2S) smells like a hell but protects cells like a heaven

This is one of the best articles I have read recently. It is not specifically about immune system, but the data are so spectacular that I have decided to write my review about it. 

It was published in journal Cell. It uncovered a new connection between benefits of dietary restriction (DR) and endogenous hydrogen sulfide production. Hydrogen Sulfide, H2S, is most known as rotten egg gas. It smells really horrible. This study showed that H2S protects cells from post-hypoxia (ischemia) tissue damage, called ischemia-reperfusion injury

This study, led by James Mitchell at Harvard School of Public Health, examined the benefits of dietary restriction  (DR) on liver damage model. Mice on DR for 7 days showed reduced liver damage during reperfusion phase and unexpectedly and counter intuitively this beneficial effect was reduced in presence of NAC, a cysteine donor and wellknown anti-oxidant molecule (since liver damage was measured by analyses of enzymes released during cell stress, I wonder whether their levels could have been affected by DR itself rather than indirectly).

Interestingly, vitamins  C and A, two wellknown anti-oxidant molecules, showed no such negative effect on DR. However, addition of amino acids, methionine and cysteine did reverse DR effects.

Even, on total protein-free, iso-caloric diet, addition of methionine and cysteine could reverse DR effects on liver damage

And, specifically, just addition of cysteine could reverse DR's beneficial effects on liver damage.

The authors found that H2S was one molecule from cysteine metabolic path that was selectively increased during DR in liver tissue (neither glutathione nor taurine were up-regulated during DR)

More importantly, addition of exogenous H2S could reduce liver damage even on full diet.
Additional experiments on fruit fly, worm and yeast showed that DR induced longevity in these models were associated with the increase in H2S expression.

The authors correctly pointed out that it is very strange that addition of cysteine, itself a source of H2S, can counter DR effect. The authors speculated that identification of an endogenous source of H2S production or cysteine synthesis during DR (or specifically during cysteine-deficient diet) could provide an explanation for this observation.

In summary, these results may indicate that restriction of methionine and cysteine intake could help tissues to survive ischemia-reperfusion injury. This will be very beneficial for situations like organ transplantation or management of ischemia conditions (stroke, heart attack, etc).

David Usharauli

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