Precoce and opposite response of proteasome activity after acute or chronic exposure of C. elegans to γ-radiation

Abstract

Species are chronically exposed to ionizing radiation, a natural phenomenon which can be enhanced by human activities. The induced toxicity mechanisms still remain unclear and seem depending on the mode of exposure, i.e. acute and chronic. To better understand these phenomena, studies need to be conducted both at the subcellular and individual levels. Proteins, functional molecules in organisms, are the targets of oxidative damage (especially via their carbonylation (PC)) and are likely to be relevant biomarkers. After exposure of Caenorhabditis elegans to either chronic or acute γ rays we showed that hatching success is impacted after acute but not after chronic irradiation. At the molecular level, the carbonylated protein level in relation with dose was slightly different between acute and chronic exposure whereas the proteolytic activity is drastically modified. Indeed, whereas the 20S proteasome activity is inhibited by acute irradiation from 0.5 Gy, it is activated after chronic irradiation from 1 Gy. As expected, the 20S proteasome activity is mainly modified by irradiation whereas the 26S and 30S activity are less changed. This study provides preliminaries clues to understand the role of protein oxidation and proteolytic activity in the radiation-induced molecular mechanisms after chronic versus acute irradiation in C. elegans.

Differential modification of the C. elegans proteome in response to acute and chronic gamma radiation: Link with reproduction decline

“…After chronic irradiation, a recent study of our team has shown that reproduction is the more sensitive macroscopic parameter regarding survival and growth [17]. Moreover, our first study has also highlighted that, contrary to acute irradiation, chronic irradiation from 3.3 Gy induced a decrease of the number of progeny without impacting the hatching success [4]. This could suggest that in such conditions, gametogenesis is more impacted than embryogenesis.…”

“…Indeed our first results showed that a decrease of the number of progeny associated with a decrease of the embryo hatchability occurred from and above 30 Gy of acute irradiation [4]. In this paper, the decrease of the progeny number per individual have been hypothesized to be correlated to an increase of apoptosis whereas an explanation for the decrease of hatching success can be unrepaired DNA-damage then leading to non-viable eggs.…”

“…However, mechanisms have not been fully elucidated yet; some of our team results coming from a multi-generation study revealed that, after three generations continuously irradiated, an increase of apoptosis, a decrease of the sperm cells number and an oocytes cell cycle arrest could explain this phenomenon [3]. As proteins are involved in key biological processes, including DNA repair, cell cycle control and apoptosis, as our first results have also shown that proteolytic response of cells are different between acute and chronic [4], it seems relevant to assess their global expression after both acute 5 and chronic exposure in order to better understand the toxicity mechanisms in response to ionizing radiations.…”

“…Data extrapolation from acute to chronic exposure is not always relevant, and can lead to uncertainties. Indeed, for a same dose, radio-induced effects are often different between the two irradiation modes, especially regarding the reproduction endpoint, which is an ecologically relevant parameter directly influencing population dynamics [3][4][5].…”

“…The free living nematode Caenorhabditis elegans is a particularly convenient model organism to address this environmental risk assessment based proteomic issue [14,15]. With its fully sequenced genome and its short life cycle, C. elegans has been successfully used to study acute and chronic irradiation effects and their consequences on germline development and hatching [4,[16][17][18][19].…”