Effects Of Lead Acetate On Autophagy, Apoptosis In The Rat Insuloma Cells INS-1

Background: In recent years, the prevalence of diabetes showed an increasing trend, sothat taking many reasonable controls to prevent diabetes are particularly important. Diabetesis a metabolic disease, which is characterized by high level of blood glucose, insulin secretiondecrease and insulin resistance. The reduce of pancreatic β cells play a key role in itsoccurrence and development. Pancreatic β cell reduction is usually due to apoptosis. The mostimportant factor in the pancreatic β cell apoptosis is intracellular oxidative stress. In addition,as another way to destroy cells, autophagic cell death is also arosing widly concerns.Recent studies showe that heavy metals can induce cells autophagy and apoptosis. Leadis a toxical heavy metals, because of its widespread use, many serious health problems havebeen caused in many parts of the world. Lead effect the body through a many ways, and candamage multiple systems (including nerve, blood, digestive, circulatory and urinary systems,etc.). Research shows that the lead can change the redox state of the cell, resulting inoxidative stress by promoting pancreatic β cells produce reactive oxygen species, and furtherlead pancreatic β cells apoptosis. However, can lead cause pancreatic β cell autophagy, andthe molecular mechanisms of autophagy are not yet clear. In this study, we observe thepancreatic β cell autophagy and apoptosis caused by different concentrations of lead in orderto explore its possible molecular mechanism. A theoretical basis can be provides that takingsome appropriate measures can reduce pancreatic β cell damage so as to reduce the risk oftype2diabetes. Objective: To study the effect of the environmental heavy metal pollutant lead on theautophagy and apoptosis of the rat insuloma cells INS–1and their probable molecularmechanisms.Methods: The rat insuloma cells INS–1were exposed to lead acetate with differentconcentration, the viabilities of insuloma cells INS–1were determined by sulforhodamine Bassay; Western blot analysis was performed to detect the expression of the markers ofautophagy and apoptosis and the related proteins of mammalian target of rapamycin; reactiveoxygen species kit was used to detect the intracellular ROS; use ROS scavengerN–acetylcysteine pretreated the cells to determine the effects of lead on the autophagy andapoptosis of INS–1cells. Analyzing the results with statistical software SPSS17.0.Results: Compared with the control group, the viability of INS–1cells treated with leadacetate decreased in a time and dose–dependent manner (p<0.05); the expression ofautophagy and apoptosis markers were enhanced with increasing the concentration of leadacetate. However, the markers of mTOR signal chain were no significant change. It wasinteresting to found that the effect of lead on the autophagy and apoptosis of INS–1cells weredecreased after they were pretreated with NAC.Conclusions: Lead acetate may induce autophagy and apoptosis in INS–1cells via amTOR–independent pathway, the probable mechanism was stimulating an increase of ROS.