Apolipoprotein A-I mimetic peptide D4F protects macrophages from oxi-dized low-density lipoprotein-induced apoptosis by inhibiting caspase-12
10.3969/j.issn.1000-4718.2015.10.004
- VernacularTitle: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
- Author:
Hua TIAN
;
Yanyan LI
;
Mingde DING
;
Nana YANG
;
Peng JIAO
;
Hui SANG
;
Yongqi FANG
;
Shutong YAO
;
Shucun QIN
- Publication Type:Journal Article
- Keywords:
ApolipoproteinA-ImimeticpeptideD4F;
Caspase-12;
Oxidizedlow-densitylipoprotein;
Macro-phage;
Apoptosis
- From:
Chinese Journal of Pathophysiology
2015;(10):1750-1755
- CountryChina
- Language:Chinese
-
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.
