Molecular Mechanism Of The ACY-1 Signaling Regulating Hyperosmotic Stress Response In C. Elegans

acy-1,encoding adenylate cyclase,is a member of adenylate cyclases family in the Caenorhabditis elegans.It can catalyze Adenosine triphosphate(ATP)into adenosine 3'5'-cyclic monophosphate(cAMP).When acy-1 is inhibited,the level of intracellular cAMP decrease.cAMP is a ubiquitous second messenger that mediates a diverse range of cellular processes,including stress responses.Stress is the specific or non-specific response to adapt to various unfavorable factors in the living environment.It is a manifestation of adaptivity.Moderate stress can improve the adaptability,while long-term durative or high-intensity stress will lead to the disorder in the internal environment and seriously affect the health,which may help the initiation and development of tumors and so on.C.elegans is widely used as a model organism for its unique advantages,such as rapid propagation and easy gene operation techniques.This thesis studied the role of acy-1 mutant subjected to hyperosmotic and hyperthermal environments in C.elegans.We found that acy-1 increased survival rates under hypertonic and heat shock conditions,and acy-1-overexpression animals did not increase stress resistance of high-salt.Then we explored the molecular mechanism.We confirmed that acy-1 mutant increased survival of nematodes in hypertonic environments via cAMP/EPAC-1/PLC-1 pathway not KIN-1.And acy-1 mutant resistance to heat shock not via cAMP/EPAC-1/PLC-1 pathway.Furthermore,We found that autophagy was induced both high-salt and high temperature conditions.In addition,knockdown of acy-1,epac-1,plc-1 induced autophagy under normal condition.And under high-salt condition,knockdown of acy-1,epac-1,plc-1 increased autophagy.Autophagy gene was required to resistence to hypertonic condition.While knockdown of acy-1 did not change the level of autophagy under heat shock condition.Finally,We examined the content of glycerol of acy-1,epac-1,and plc-1 mutant under hypertonic conditions.It was found that the glycerol content of acy-1,epac-1,and plc-1 mutant has no significant change under high-salt condition,whereas the glycerol content decreased significantly in acy-1-overexpression animals.Therefore,we think that cAMP/EPAC-1/PLC-1 pathway may regulate the level of glycerol.This thesis demobstrated a new pathway regulating hyperosmotic stress response in C.elegans.When worms are exposed to hypertonic condition,cAMP/EPAC-1/PLC-1 pathway is suppressed,then increase autophagy to resist hypertonic condition.The study of hyperosmotic stress response in C.elegans will help us know more about the mechanism of hyperosmotic stress response,it will also help us explore the complex links between stress response and human diseases.