Effects Of Caenorhabditis Elegans Gbb-1Mutations On Stress Resistance

Prolonging lifespan and delaying senescence is the long-cherished common wish ofhuman beings, so aging and longevity has became the most popular subject in life scienceresearch. Due to its short lifecycle and the easiness to cultivate and observe, theCaenorhabditis elegans (C.elegans) becomes the preferred model organism in life scienceresearch especially in aging research. Aging is the result of gene and environment. Avariety of theory have been proposed to explain the facts that several mutants in C.eleganscan extend the lifespan. Gamma-aminobutyric (GABA) is the major inhibitoryneurotransmitter in the central nervous system. One of important metabotropic GABAreceptor is GABABreceptor which belongs to class C of G-protein coupled receptors(GPCRs) and plays a key role in regulating neuronal excitability.The aging process, like other biological processes, is regulated by classical signalingpathways and many transcription factors. In this study, we developed several approach totest the resistance of C.elegans against environmental stress. We found the associationbetween such a wide-expressed GPCR and the resistance against environmental stress bytesting sensitivity to ultraviolet radiation and PA14infection of a loss-of-function allele,gbb-1(tm1406). These mutants elevated the resistance against stress. And for the mutantsof unc-25, which encode GABA biosynthetic enzyme, also elevated the resistance againstenvironmental stress.DAF-16is the sole ortholog of the FOXO transcription factor family in the C.elegans.Previous study shown DAF-16is a critical factor in prolonging lifespan and promotingresistance in many age mutants. To affirm whether daf-16is required for the promotingresistance of gbb-1worms, we use gbb-1, daf-16double mutants. The results shown therewas the same resistance against environmental stress as daf-16mutants, which indicatedthe effects of gbb-1mutations on stress resistance was dependent on the transcriptionalfactor DAF-16/FOXO.In summary, our study shown loss-of-function gbb-1mutants can elevate stressresistance via a daf-16depended pathway after UV radiation and PA14infection, and themutants of unc-25, another GABA-associated gene, was shown the same effect. These results will contribute to improve our understanding of GABABR and its evolutionarydevelopment in C.elegans and mammalian.