Ceramide mediates radiation-induced germ cell apoptosis via regulating mitochondria function and MAPK factors in Caenorhabditis elegans

Abstract

Studies about radiation damage in vivo are very significant for healthy risk assessment as well as cancer radiotherapy. Ceramide as a second messenger has been found to be related to radiation-induced apoptosis. However, the detailed mechanisms in living systems are still not fully understood. In the present study, the effects of ceramide in gamma radiation-induced response were investigated using Caenorhabditis elegans. Our results indicated that ceramide was required for gamma radiation-induced whole-body germ cell apoptosis by the production of radical oxygen species and decrease of mitochondrial transmembrane potential. Using genetic ceramide synthase-related mutated strains and exogenous C16-ceramide, we illustrated that ceramide could regulate DNA damage response (DDR) pathway to mediate radiation-induced germ cell apoptosis. Moreover, ceramide was found to function epistatic to pmk-1 and mpk-1 in MAPK pathway to promote radiation-induced apoptosis in Caenorhabditis elegans. These results demonstrated ceramide could potentially mediated gamma radiation-induced apoptosis through regulating mitochondrial function, DDR pathway and MAPK pathway.

Keywords

• Ceramide
• Gamma irradiation
• DNA damage response
• Mitochondria function
• Caenorhabditis elegans