Increasing extracellular H2O2 produces a bi-phasic response in intracellular H2O2, with peroxiredoxin hyperoxidation only triggered once the cellular H2O2-buffering capacity is overwhelmed

Reactive oxygen species, such as H2O2, can damage cells but also promote fundamental processes, including growth, differentiation and migration. The mechanisms allowing cells to differentially respond to toxic or signaling H2O2 levels are poorly defined. Here we reveal that increasing external H2O2 produces a bi-phasic response in intracellular H2O2. Peroxiredoxins (Prx) are abundant peroxidases which protect against genome instability, ageing and cancer. We have developed a dynamic model simulating in vivo changes in Prx oxidation. Remarkably, we show that the thioredoxin peroxidase activity of Prx does not provide any significant protection against external rises in H2O2. Instead, our model and experimental data are consistent with low levels of extracellular H2O2 being efficiently buffered by other thioredoxin-dependent activities, including H2O2-reactive cysteines in the thiol-proteome. We show that when extracellular H2O2 levels overwhelm this buffering capacity, the consequent rise in intracellular H2O2 triggers hyperoxidation of Prx to thioredoxin-resistant, peroxidase-inactive form/s. Accordingly, Prx hyperoxidation signals that H2O2 defenses are breached, diverting thioredoxin to repair damage

Enhanced 3He 4He ratios and cosmogenic helium in ultramafic xenoliths

Recently erupted ultramafic xenoliths generally have ratios of 3He 4He = (5-10) × RA, which are similar to the values characterizing mid-ocean ridge basalts (MORB). During the course of additional investigations of ultramafic xenoliths, samples from several locations have been found with 3He 4He ratios of either whole rock or mineral separates that are substantially higher than those found in MORB, up to over 400 × RA. These elevated ratios correspond to 3He excesses of between 8·10-14 and 2·10-12 cm3 STP g-13He, assuming that the samples initially contained He with an isotopic composition similar to that of MORB and other xenoliths from the sample localities. These excesses are consistent with a derivation from in situ cosmic-ray spallation, considering the production rates for the particular latitudes, altitudes, and exposure ages involved. These results demonstrate that cosmogenic He identified in samples from Maui can be found in significant quantities in other geological samples that have been used to characterize mantle He. © 1987