Research On The Mechanism Of Cadmium Regulating Endogenous Apoptosis And Mitophagy Via Intracellular Calcium Ions In HL7702 Cells

Cadmium（Cd）is a widespread toxic heavy metal which could enter into the body and cause various diseases.Meanwhile,Cd has potential carcinogenicity and could lead to cellular transformation,tumor development and proliferation of a variety of organs including liver.Simultaneously,Cd has a long biological half-life accumulating in the body,so the cadmium exposure has a great risk to human health and its toxic mechanism is an important content of toxicology research.Cd induces apoptosis and autophagy through intracytoplasmic calcium ions but effects of calcium in endogenous apoptosis and mitophagy are not clear.The cores of endogenous apoptosis and mitophagy are all the mitochondria,Cd could cause mitochondrial damage which is the basis of two kinds of different events above.But the forming process of mitochondrial autophagy body will inhibit the release of cytochrome C（Cyt C）from mitochondria to cytoplasm which is the initiation of endogenous apoptosis.Therefore,mitophagy is the opposite of endogenous apoptosis but the role of intracellular calcium ions in this opposite relationship is not clear.This study selected HL7702 cells as experimental material.HL7702 cells were respectively pre-treated with intracellular calcium chela tor Bapta-AM,autophagy inhibitor U0126-Et OH and JNK inhibitor SP600125,detected with techniques such as cell viability analysis,immunoblotting,cell fluorescence and flow cytometry to explore the function of intracellular Ca²⁺in mitophagy and endogenous apoptosis.The results showed that:1.Cd induced rise of Ca²⁺concentration in a relatively short time in HL7702 cells,this concentration would decrease with time extension;2.Cd promoted endogenous apoptosis in HL7702 cells by intracellular Ca²⁺;3.Cd restrained mitophagy in HL7702 cells by intracellular Ca²⁺;4.The regulations of Ca²⁺on mitophagy and autophagy were different;5.Cd influenced phosphorylation of Bim by intracellular Ca²⁺;6.JNK involved in inhibition of mitophagy induced by Cd in HL7702 cells.In conclusion,intracellular Ca²⁺restrained mitophagy with the processing of endogenous apoptosis induced by Cd in HL7702 cells,JNK involved in this restraint.