Allicin attenuates macrophage-derived foam cell apoptosis by inhibiting caspase-12 / 中国病理生理杂志

ABSTRACT

AIM:To investigate the inhibitory effect of allicin on apoptosis and caspase-12 activation of macro-phage-derived foam cells,and to elucidate the underlying molecular mechanisms. METHODS:RAW264.7 macrophages were pretreated with allicin (12.5,25 and 50 mg/L) or 4-phenylbutyric acid(PBA,4 mmol/L) for 1 h and then treated with oxidized low-density lipoprotein(ox-LDL,100 mg/L) or tunicamycin(TM,4 mg/L) for 24 h. The cell viability and apoptosis were examined by MTT assay and flow cytometry with Annexin V-FITC/PI staining,respectively. The activities of caspase-3 in the cells and lactic dehydrogenase (LDH) in the medium were measured. The protein levels of caspase-12 were determined by Western blot. The intracellular lipid accumulation was measured with oil red O staining and the content of intracellular total cholesterol was determined by enzymatic colorimetry. RESULTS:Similar to the endoplasmic reticulum stress (ERS) inhibitor PBA, allicin inhibited ox-LDL-induced injury of RAW264.7 macrophages in a concentration-de-pendent manner,as determined by the increased cell viability and the decreased LDH leakage,apoptosis and caspase-3 ac-tivity. The decrease in cell viability and increases in LDH leakage and apoptosis induced by TM (an ERS inducer) were also suppressed by allicin. Moreover, similar to PBA, allicin remarkably inhibited ox-LDL- or TM-induced activation of caspase-12. Furthermore, allicin remarkably attenuated ox-LDL-induced lipid accumulation in the RAW264.7 cells and foam cells formation in a concentration-dependent manner. CONCLUSION:Allicin may inhibit macrophage-derived foam cell apoptosis induced by ox-LDL,and the mechanism is partially related to suppressing the activation of caspase-12.