中国病理生理杂志Issue(10)：1750-1755,6.DOI:10.3969/j.issn.1000-4718.2015.10.004
载脂蛋白 A－I 模拟肽 D4 F 通过抑制 caspase－12减轻氧化低密度脂蛋白诱导的巨噬细胞凋亡
Apolipoprotein A-I mimetic peptide D4F protects macrophages from oxi-dized low-density lipoprotein-induced apoptosis by inhibiting caspase-12
摘要
Abstract
[ABSTRACT]AIM:ToinvestigatetheeffectofD4F,anapolipoproteinA-Imimeticpeptide,onoxidizedlow-density lipoprotein ( ox-LDL)-induced macrophage apoptosis and activation of caspase-12, a key molecule in endoplasmic reticulum stress ( ERS )-associated apoptotic pathway, and to elucidate the underlying molecular mechanisms. METHODS:RAW264.7 macrophages were pretreated with D4F (12.5, 25 and 50 mg/L), 4-phenylbutyric acid (PBA, 5 mmol/L) or diphenyleneiodonium ( DPI, 5 μmol/L) for 1 h and then treated with ox-LDL (100 mg/L) or tunicamycin ( TM, 4 mg/L) for 24 h.The cell viability and apoptosis were determined by MTT assay and TUNEL detection, respective-ly.The levels of malondialdehyde ( MDA) and reactive oxygen species ( ROS) in the cells and the activities of superoxide dismutase ( SOD) and nicotinamide adenine dinucleotide phosphate ( NADPH) oxidase were determined.The protein level of caspase-12 was examined by Western blot analysis.RESULTS: Similar to the ERS inhibitor PBA, D4F protected RAW264.7 macrophages from ox-LDL or TM ( an ERS inducer)-induced decrease in the viability and increase in apoptotic rate in a dose-dependent manner.Like DPI (an oxidative stress inhibitor), D4F significantly inhibited ox-LDL-induced ox-idative stress, as expressed by the decreased generation of ROS and MDA ( P<0.01) , the increased activity of SOD and the decreased activity of NADPH oxidase (P<0.05).Moreover, similar to PBA and DPI, D4F significantly suppressed ox-LDL-induced activation of caspase-12 in a concentration-dependent manner ( P<0.05) .Furthermore, D4F also inhibi-ted the caspase-12 activation induced by TM (P<0.05).CONCLUSION: D4F inhibits macrophage apoptosis induced by ox-LDL, and the mechanism is at least partially by reducing oxidative stress and inhibiting the activation of caspase-12.关键词
载脂蛋白A-I模拟肽D4F/Caspase-12/氧化低密度脂蛋白/巨噬细胞/细胞凋亡Key words
ApolipoproteinA-ImimeticpeptideD4F/Caspase-12/Oxidizedlow-densitylipoprotein/Macro-phage/Apoptosis分类
医药卫生引用本文复制引用
田华,李严严,丁明德,杨娜娜,焦鹏,桑慧,方永奇,姚树桐,秦树存..载脂蛋白 A－I 模拟肽 D4 F 通过抑制 caspase－12减轻氧化低密度脂蛋白诱导的巨噬细胞凋亡[J].中国病理生理杂志,2015,(10):1750-1755,6.基金项目
国家自然科学基金资助项目（ No．81202949；No．81370381）；山东省自然科学基金联合专项（ No． ZR2014HL013）；山东省医药卫生科技发展计划 （）
