Study On Environmental Cadmium Induced Autophagy And Apoptosis In Chronic Obstructive Pulmonary Disease Patients

Objective Environmental cadmium is closely correlated with several respiratory diseases.Exposured to dust which containing cadium in the occupational environment would increases the incidence of chronic obstructive pulmonary disease（COPD）.The pathogenesis of COPD mainly includes chronic inflammation,protease-antiprotease hypothesis,REDOX imbalance,excessive apoptosis and ineffective repair.Pulmonary autophagy and apoptosis play significant roles in the pathophysiological process of COPD.Nevertheless,the correlations of cadmium exposure with autophagy and apoptosis are obscure in patients with COPD.The main purpose of this research was to explore the correlations among serum cadmium,pulmonary function,pulmonary autophagy and apoptosis in patients with COPD through a case-control study.Methods All 300 patients diagnosed with COPD in Department of Respiratory Medicine in the Second Affiliated Hospital of Anhui Medical University in China were recruited.All 300 control cases were recruited from the Physical Examination Center in hospital.Each patient was paired with a control case on the basis of sex and age.Patients with other pulmonary diseases were excluded in this research.Serum samples were collected from COPD patients and control cases.Serum cadmium was detected with graphite furnace atomic absorption spectrometry.Human CRP,MCP-1,TNF-α,IL-6 were measured by ELISA.To determine the levels of autophagy and apoptosis between COPD patients and control subjects,31lung tissues from COPD patients were obtained during surgery.The protein expression of autophagy（P62,Beclin 1,LC3 II and I）and apoptosis（caspase1,caspase 3,cleaved Caspase 1 and 3）were measured in lungs using western blotting.TUNEL assay was performed to access cellular apoptosis through Dead End^TM Colorimetric TUNEL System.BEAS-2B cells were co-cultured with cadmium（Cadmium chloride,Cd Cl2）at the concentration of 0.4μM.After different times,cells were harvested.Moreover,in order to evaluate the changes of autophagic flux,the effect of Bafilomycin A1 on cadmium-activated autophagy was determined in BEAS-2B cells.BEAS-2B cells were pretreated with Bafilomycin A1 for 2 h prior to cadmium exposure.Then BEAS-2B cells were exposed to cadmium.After 12 h,BEAS-2B cells were harvested and autophagic flux was detected using western blotting.Results These results indicated that serum cadmium was higher in COPD patients than control cases.Serum cadmium was gradually risen parallelly with the grades of COPD patients.P62,Beclin 1,LC3 II and I,the markers of autophagy,was elevated in lungs of COPD patients.Addi-tionally,cleaved Caspase 1 and 3,as well as TUNEL positive cells,the molecules of apoptosis,were increased in lungs of COPD patients.In addition,correlational analysis indicated that serum cadmium was positively asso-ciated with autophagy and apoptosis in lungs among COPD patients.Besides,pulmonary autophagy and apoptosis were inversely correlated with pulmonary function in COPD patients.In vitro experiments revealed that P62,Beclin 1,LC3 II and I,cleaved Caspase 1 and 3 were increased with the extension of cadmium treatment time.The expressions of autophagy markers P62,Beclin 1,LC3 II and I all increased in Baf A1 and Cadmium-treated cells.Conclusion Environmental cadmium exposure is positively correlated with autophagy activation and apoptosis elevation in COPD patients.Serum cadmium is positively correlated with pulmonary function decline among COPD patients.Besides,serum higher cadmium is correlated with autophagy activation and apoptosis elevation in lungs of COPD patients.In addition,autophagy activation and apoptosis elevation in lungs are positively correlated with pulmonary function decline among COPD patients.Further in vivo research suggested that cadmium exposure activates autophagy and elevates apoptosis in human pulmonaryepithelial cells.In conclusions,it should be taken into consideration to alleviate exogenous cadmium exposure from potential environmental sources to prevent human bodies from pulmonary function decline caused by autophagy activation and apoptosis elevation in lungs.