Picking up on that reactive oxygen species (ROS) business from the other day (James Watson's paper suggesting that it could be a key anticancer pathway), I wanted to mention this new paper, called to my attention this morning by a reader. It's from a group at Manchester studying regeneration of tissue in Xenopus tadpoles, and they note high levels of intracellular hydrogen peroxide in the regenerating tissue. Moreover, antioxidant treatment impaired the regeneration, as did genetic manipulation of ROS generation.

Now, inflammatory cells are known to produce plenty of ROS, and they're also involved in tissue injury. But that doesn't seem to be quite the connection here, because the tissue ROS levels peaked before the recruitment of such cells did. (This is consistent with previous work in zebrafish, which also showed hydrogen peroxide as an essential signal in wound healing). The Manchester group was able to genetically impair ROS generation by knocking down a protein in the NOX enzyme complex, a major source of ROS production. This also impaired regeneration, an effect that could be reversed by a rescue competition experiment.

Further experiments implicated Wnt/bet-catenin signaling in this process, which is certainly plausible, given the position of that cascade in cellular processes. That also ties in with a 2006 report of hydrogen peroxide signaling through this pathway (via a protein called nucleoredoxin.

You can see where this work is going, and so can the authors:

. . .our work suggests that increased production of ROS plays a critical role in facilitating Wnt signalling following injury, and therefore allows the regeneration program to commence. Given the ubiquitous role of Wnt signalling in regenerative events, this finding is intriguing as it might provide a general mechanism for injury-induced Wnt signalling activation across all regeneration systems, and furthermore, manipulating ROS may provide a means to induce the activation of a regenerative program in those cases where regeneration is normally limited.

Most of us reading this site belong to one of those regeneration-limited species, but perhaps it doesn't always have to be this way? Taken together, it does indeed look like (1) ROS (hydrogen peroxide among others) are important intracellular signaling molecules (which conclusion has been clear for some time now), and (2) the pathways involved are crucial growth and regulatory ones, relating to apoptosis, wound healing, cancer, the effects of exercise, all very nontrivial things indeed, and (3) these pathways would appear to be very high-value ones for pharmaceutical intervention (stay tuned).

As a side note, Paracelsus has once again been reaffirmed: the dose does indeed make the poison, as does its timing and location. Water can drown you, oxygen can help burn you, but both of them keep you alive.